The use of spiro [2.4]hepta-4,6-diene-1-methanol 7 as a general precursor for the\r\nsynthesis of highly functionalized cyclopentyl rings is described. Diene 7 was converted\r\nto its silyl protected 4-nitrile derivative 24 in 46% overall yield. The cyclopropyl ring of\r\n24 reacted with soft carbanionic nucleophiles to give ring opened homo-conjugate\r\naddition products 25a-h in 76-97% yield without loss of optical purity. The addition\r\nproducts could be further manipulated by selective mono-hydrogenation to give 1,2\r\nsubstituted cyclopentenes 26a-e in 85-96% yield.
\r\n\r\nDiene 7 was used as a starting material for studies directed toward the synthesis\r\nof the stereochemically dense chloro-cyclopentyl core of palau'amine 1. Two advanced\r\nintermediates 50 and 72 were synthesized. Attempts to effect intramolecular chlorine\r\ntransfer with 50 were unsuccessful. Attempted intramolecular chlorine transfer with 72\r\nled, instead, to an oxygenated species resulting from oxygen radical trapping.
\r\n\r\nThe enantioselective synthesis of the stereochemically dense chloro-cyclopenty l\r\ncore of axinellamines A-D 2-5 starting from 7 is also described. The core is synthesized\r\nin 4.6% yield over 24 steps. Nakamura's radical dehalogenative hydroxylation is applied\r\nfor the first time to a cyclopropyl carbonyl iodide to give the ring-opened product in 86%\r\nyield. Bolm's meso-anhydride desymmetrization is used to introduce asymmetry in a\r\nnorbornene intermediate. The final step is a diastereoselective intermolecular\r\nchlorination using Barton's methodology to achieve chlorine transfer in 76% yield.
\r\n", "doi": "10.7907/114f-cx28", "publication_date": "2001", "thesis_type": "phd", "thesis_year": "2001" }, { "id": "thesis:8164", "collection": "thesis", "collection_id": "8164", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:03252014-083524220", "primary_object_url": { "basename": "Mish-mr-2001.pdf", "content": "final", "filesize": 28097360, "license": "other", "mime_type": "application/pdf", "url": "/8164/1/Mish-mr-2001.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "The Application of Trimethylsilyl Diazomethane to the Synthesis of Optically Active Pyrazolines and Related Studies", "author": [ { "family_name": "Mish", "given_name": "Michael Robert", "clpid": "Mish-Michael-Robert" } ], "thesis_advisor": [ { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" } ], "thesis_committee": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "orcid": "0000-0003-1464-2461", "clpid": "Dougherty-D-A" }, { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" }, { "family_name": "Dervan", "given_name": "Peter B.", "orcid": "0000-0001-8852-7306", "clpid": "Dervan-P-B" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The 1,3-dipolar cycloadditions of trimethylsilyl diazomethane with camphorsultam-derived acrylates are reported as a means for the efficient synthesis of optically active pyrazolines. Trimethylsilyl diazomethane is a safe, commercially available diazoalkane which provides \u03941-pyrazolines 1n good yield and diastereoselectivity when camphorsultam-derived acrylates are used as the reaction dipolarophiles . These initial cycloadducts are subsequently converted to stable, characterizable \u03942-pyrazolines upon desilylation.
\r\n\r\nA manifold of reactions that can be applied to these \u03942-pyrazolines has been developed which includes pyrazoline reduction, N-N bond reduction, addition to the pyrazoline C=N by mild carbon nucleophiles, and both solvolytic and reductive chiral auxiliary removal. Additionally, it has been demonstrated that the pyrazoline reduction products can take part in peptide coupling reactions that allow for the pyrazolidines to serve as proline-like molecules. The development of this methodology is a general solution to the problem of highly substituted, functionalized pyrazoline synthesis. Importantly, the pyrazolines thus provided have been demonstrated to be amenable to reactions that add to their value as synthetic intermediates.
\r\n", "doi": "10.7907/s6ej-q525", "publication_date": "2001", "thesis_type": "phd", "thesis_year": "2001" }, { "id": "thesis:11084", "collection": "thesis", "collection_id": "11084", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:06142018-101514702", "primary_object_url": { "basename": "Maughon_BR_1998.pdf", "content": "final", "filesize": 55184505, "license": "other", "mime_type": "application/pdf", "url": "/11084/1/Maughon_BR_1998.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Synthesis of Functionalized Polymers by Ring-Opening Metathesis Polymerization (ROMP)", "author": [ { "family_name": "Maughon", "given_name": "Bob Robinson, Jr.", "clpid": "Maughon-Bob-Robinson-Jr" } ], "thesis_advisor": [ { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" } ], "thesis_committee": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "clpid": "Barton-J-K" }, { "family_name": "Carreira", "given_name": "Erick Moran", "clpid": "Carreira-E-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "In Chapter 1, the ROMP of 5-methacrylate-1-cyclooctene and the copolymerization\r\nof this monomer with cyclooctadiene using the initiator (PCy3)2Cl2Ru=CHCH=CPh2 were\r\ninvestigated to produce polymers with cross-linkable side-chains. The impact of\r\nconcentration, monomer to initiator ratio, and the amount of inhibitor in the polymerization\r\nwas examined. These polymers were cross-linked through the methacrylate side-chains\r\nwith either thermal or photochemical initiation, and the incorporation of these polymers into\r\npoly(methyl methacrylate) (PMMA) to produce AB cross-linked materials was\r\naccomplished. A comparison of the physical properties of PMMA and these new materials\r\ndemonstrated that these materials had higher thermal stability and solvent resistance than\r\npure PMMA.
\r\n\r\n\r\nAs an extension of the work presented in Chapter 1, Chapter 2 illustrated an\r\nalternative approach for the preparation of cross-linkable polymers by ROMP. The\r\nsynthesis of ring-opening metathesis polymerization chain transfer agents bearing\r\nmethacrylate and epoxide end-functionality was accomplished. In the presence of these\r\nchain transfer agents, cyclooctadiene was polymerized via a ruthenium benzylidene\r\ninitiator, (PCy3)Cl2Ru=CHPh, to produce telechelic poly(butadiene)s with either\r\nmethacrylate or epoxide end groups. The impact of initiator concentration, reaction time,\r\nand temperature on the polymer yield and chain transfer agent incorporation was examined.\r\nControl over the polymer molecular weight through the cyclooctadiene/chain transfer agent\r\nratio was demonstrated providing for a range of telechelic poly(butadiene) molecular\r\nweights. Successful cross-linking of these polymers by thermal or photochemical initiation\r\nin the case of the bis(methacrylate)-functionalized telechelic poly(butadiene)s or through\r\nacid catalysis in the case of the bis(epoxide)-functionalized telechelic poly(butadiene)s was\r\naccomplished.
\r\n\r\n\r\nIn an effort to further explore the functional group tolerance of the ruthenium-based\r\nmetathesis initiators developed in our group, the investigation presented in Chapter 3\r\nencompassed the synthesis and living ring-opening metathesis polymerization (ROMP) of\r\nsubstituted cyclobutenes with the functional group tolerant polymerization initiators\r\n(PCy3)2Cl2Ru=CHCH=CPh2 and (PCy3)2Cl2Ru=CHPh. Synthetic methodology was\r\ndeveloped for the synthesis of a wide variety of 3-functionalized cyclobutenes containing\r\nether, ester, alcohol, amine, amide, and carboxylic acid substituents. Coordination of these\r\nfunctional groups to the propagating carbene was observed resulting in the formation of a\r\nchelated propagating species with concomitant loss of one phosphine ligand from the metal\r\ncenter. Studies aimed at understanding this chelation and its effect on the polymerization\r\nwere undertaken. Based on these results, the synthesis of a series of functionalized\r\ncyclobutenes was accomplished which minimized this chelation and allowed for living\r\npolymerizations. A new class of functionalized poly(butadiene) homopolymers and\r\ndiblock copolymers was synthesized and the thermal properties analyzed by\r\nthermogravimetric analysis and differential scanning calorimetry.
\r\n\r\n\r\nIn Chapter 4, the effect of backbone flexibility on the mesomorphic behavior of\r\nside-chain liquid crystalline polymers synthesized by ring-opening metathesis\r\npolymerization was investigated. The synthesis of norbornene and cyclobutene monomers\r\ncontaining a p-nitrostilbene moiety as the mesogenic group and polymerization of these\r\nmonomers with the metathesis initiator (PCy3)2Cl2Ru=CHPh to produce side-chain liquid\r\ncrystalline polymers with low polydispersities and defined molecular weights was\r\naccomplished. The relatively rigid poly(norbornene)s displayed enantiotropic nematic\r\nmesomorphism with glass transitions from 44-64\u00b0C and isotropization temperatures\r\nbetween 108-121\u00b0C, whereas the more flexible poly(butadiene)s showed enantiotropic\r\nsmectic A mesomorphism with glass transition temperatures from 14-31\u00b0C and\r\nisotropization temperatures between 74-111\u00b0C. A diblock copolymer containing a 1:1\r\nmixture of the poly(norbornene) and poly(butadiene) backbones also exhibited a smectic A\r\nmesophase. The dependence of the degree of polymerization and flexible spacer length on\r\nthe phase transitions of these systems was determined demonstrating stabilization of the\r\nmesophase by both increasing molecular weight and flexible spacer length.
\r\n\r\n\r\nA short chapter on the development of methodology for an improved synthesis of\r\n3-methyl-3-phenylcyclopropene was included in Appendix 1. This research was\r\ninvestigated in hopes of developing a more facile and inexpensive procedure for the\r\npreparation of this compound than has been previously reported. Phase transfer catalyzed\r\ndichlorocarbene addition to \u03b1-methylstyrene followed by a selective catalytic Bu3SnH\r\nreduction resulted in the 1-chloro-2-methyl-2-phenylcyclopropane intermediate in excellent\r\nyield. Base-induced elimination of this compound resulted in the desired 3-methyl-3-phenylcyclopropene. \r\nThis approach allowed for the preparation of this cyclopropene on\r\nlarge scale utilizing inexpensive reagents.
\r\n\r\n\r\n\r\n\r\n", "doi": "10.7907/txks-pt47", "publication_date": "1998", "thesis_type": "phd", "thesis_year": "1998" }, { "id": "thesis:17582", "collection": "thesis", "collection_id": "17582", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07312025-221339661", "primary_object_url": { "basename": "Wagaman_MW_1998.pdf", "content": "final", "filesize": 62992040, "license": "other", "mime_type": "application/pdf", "url": "/17582/1/Wagaman_MW_1998.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Conjugated Electroluminescent Polymers Synthesized by a Ring-Opening Metathesis Polymerization Precursor Route", "author": [ { "family_name": "Wagaman", "given_name": "Michael Wayne", "clpid": "Wagaman-Michael-Wayne" } ], "thesis_advisor": [ { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" } ], "thesis_committee": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "orcid": "0000-0003-1464-2461", "clpid": "Dougherty-D-A" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" }, { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "A variety of substituted poly(para-phenylenevinylene) (PPVs) and poly(l,4-\r\nnaphthalenevinylene) homopolymers, block copolymers and random copolymers have been\r\nsynthesized by a ring-opening metathesis polymerization (ROMP) precursor route. In\r\ngeneral the initiator Mo=CCH(CH3)2Ph(=NAr)(OCCH3(CF3)2)2, 1, was used to polymerize barrelene (bicyclo[2.2.2]octatriene) and benzobarrelene monomers. The\r\nprecursor polymers obtained were then aromatized in solution using 2,3-dichloro-5,6-\r\ndicyanobenzoquinone (DDQ) to produce PPVs and PNVs, many of which are soluble in\r\ncommon organic solvents.
\r\n\r\nTo prepare these polymers, new syntheses of the monomers were first developed as\r\ndescribed in Chapters 1 and 2. The routes developed readily allow the preparation of a\r\nvariety of substituted benzobarrelene and barrelene monomers in multigram quantities. As\r\ndescribed in Chapter 3, several well-defined metathesis initiators were tested to determine\r\nthe one best suited to the synthesis of homopolymers and copolymers of the monomers\r\nprepared. Tuning of the activity of 1 to achieve a living polymerization is also described.
\r\n\r\nIn Chapter 4 the synthesis of PNV and PPV homopolymers, and studies of their\r\nabsorbance and fluorescence properties, are described. These studies show that the\r\ndifferent homopolymers exhibit luminescence from the blue (450 nm) to nearly the red (580\r\nnm) depending on the substituents on the polymer, which were usually alkyl groups,\r\nelectron withdrawing groups (halogens, esters, and perfluoroalkyl groups) or both.\r\nPolymers with electron withdrawing groups were found to be much more stable in air than\r\nunsubstituted PPV and PNV.
\r\n\r\nThe synthesis of PNV and PPV random and block polymers and studies of their\r\nabsorbance and fluorescence properties are described in Chapter 5. In general, polymers\r\nwith a diblock or blocky distribution of monomer units showed migration of excitons\r\n(electron-hole pairs) into the smaller bandgap segments of the polymer. As a result, most\r\nof the luminescence from these materials had a wavelength characteristic of the smaller\r\nbandgap homopolymer. More efficient transport was observed in films and in copolymers\r\nwith shorter block segments.
\r\n\r\nIn Chapter 6 the results of electroluminescence studies with three of the polymers\r\nare described. These measurements show that the polymers prepared exhibit\r\nelectroluminescence. They also reveal that alkylated PNV is a better hole transporter than\r\nelectron transporter but that diester substituted PPV is a better electron transporter and a\r\npoorer hole transporter.
\r\n\r\nFinally, use of a di-t-butylester substituted PPV in conjunction with a photo-acid\r\ngenerator as a photoresist is described in the Appendix.
", "doi": "10.7907/65pj-3w78", "publication_date": "1998", "thesis_type": "phd", "thesis_year": "1998" }, { "id": "thesis:17582", "collection": "thesis", "collection_id": "17582", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07312025-221339661", "primary_object_url": { "basename": "Wagaman_MW_1998.pdf", "content": "final", "filesize": 62992040, "license": "other", "mime_type": "application/pdf", "url": "/17582/1/Wagaman_MW_1998.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Conjugated Electroluminescent Polymers Synthesized by a Ring-Opening Metathesis Polymerization Precursor Route", "author": [ { "family_name": "Wagaman", "given_name": "Michael Wayne", "clpid": "Wagaman-Michael-Wayne" } ], "thesis_advisor": [ { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" } ], "thesis_committee": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "orcid": "0000-0003-1464-2461", "clpid": "Dougherty-D-A" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" }, { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "A variety of substituted poly(para-phenylenevinylene) (PPVs) and poly(l,4-\r\nnaphthalenevinylene) homopolymers, block copolymers and random copolymers have been\r\nsynthesized by a ring-opening metathesis polymerization (ROMP) precursor route. In\r\ngeneral the initiator Mo=CCH(CH3)2Ph(=NAr)(OCCH3(CF3)2)2, 1, was used to polymerize barrelene (bicyclo[2.2.2]octatriene) and benzobarrelene monomers. The\r\nprecursor polymers obtained were then aromatized in solution using 2,3-dichloro-5,6-\r\ndicyanobenzoquinone (DDQ) to produce PPVs and PNVs, many of which are soluble in\r\ncommon organic solvents.
\r\n\r\nTo prepare these polymers, new syntheses of the monomers were first developed as\r\ndescribed in Chapters 1 and 2. The routes developed readily allow the preparation of a\r\nvariety of substituted benzobarrelene and barrelene monomers in multigram quantities. As\r\ndescribed in Chapter 3, several well-defined metathesis initiators were tested to determine\r\nthe one best suited to the synthesis of homopolymers and copolymers of the monomers\r\nprepared. Tuning of the activity of 1 to achieve a living polymerization is also described.
\r\n\r\nIn Chapter 4 the synthesis of PNV and PPV homopolymers, and studies of their\r\nabsorbance and fluorescence properties, are described. These studies show that the\r\ndifferent homopolymers exhibit luminescence from the blue (450 nm) to nearly the red (580\r\nnm) depending on the substituents on the polymer, which were usually alkyl groups,\r\nelectron withdrawing groups (halogens, esters, and perfluoroalkyl groups) or both.\r\nPolymers with electron withdrawing groups were found to be much more stable in air than\r\nunsubstituted PPV and PNV.
\r\n\r\nThe synthesis of PNV and PPV random and block polymers and studies of their\r\nabsorbance and fluorescence properties are described in Chapter 5. In general, polymers\r\nwith a diblock or blocky distribution of monomer units showed migration of excitons\r\n(electron-hole pairs) into the smaller bandgap segments of the polymer. As a result, most\r\nof the luminescence from these materials had a wavelength characteristic of the smaller\r\nbandgap homopolymer. More efficient transport was observed in films and in copolymers\r\nwith shorter block segments.
\r\n\r\nIn Chapter 6 the results of electroluminescence studies with three of the polymers\r\nare described. These measurements show that the polymers prepared exhibit\r\nelectroluminescence. They also reveal that alkylated PNV is a better hole transporter than\r\nelectron transporter but that diester substituted PPV is a better electron transporter and a\r\npoorer hole transporter.
\r\n\r\nFinally, use of a di-t-butylester substituted PPV in conjunction with a photo-acid\r\ngenerator as a photoresist is described in the Appendix.
", "doi": "10.7907/65pj-3w78", "publication_date": "1998", "thesis_type": "phd", "thesis_year": "1998" }, { "id": "thesis:17605", "collection": "thesis", "collection_id": "17605", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08082025-165811908", "primary_object_url": { "basename": "Hastings_CA_1998.pdf", "content": "final", "filesize": 79636336, "license": "other", "mime_type": "application/pdf", "url": "/17605/1/Hastings_CA_1998.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Part A. Studies Directed Toward the Total Synthesis of Chebulagic Acid. Part B. DNA Recognition by Metallointercalator-Peptide Conjugates", "author": [ { "family_name": "Hastings", "given_name": "Curtis Asa", "clpid": "Hastings-Curtis-Asa" } ], "thesis_advisor": [ { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" } ], "thesis_committee": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "orcid": "0000-0003-1464-2461", "clpid": "Dougherty-D-A" }, { "family_name": "Goddard", "given_name": "William A., III", "orcid": "0000-0003-0097-5716", "clpid": "Goddard-W-A-III" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" }, { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Part A. The development of asymmetric allene/enone and allene/enoate\r\nintramolecular [2+2]-photocycloadditions is described. Irradiation of optically active\r\nallenes (89-92% ee) appended to enones and enoates afforded alkylidenecyclobutane\r\nphotoadducts with high levels of asymmetric induction (83 -100%) derived exclusively\r\nfrom the allene fragment. Substrates examined include allenyl alcohols appended to 1,3-\r\ncyclopentanedione, 1,3-cyclohexanedione, and 4-hydroxycoumarin. The absolute sense of\r\ninduction in these reactions was determined by photocycloaddition of an allene containing\r\nan internal stereochemical label. The exa-methylenecyclobutanes obtained upon irradiation\r\nof allene-coumarins were isolated as single olefin diastereomers. A model for the high\r\nlevels of enantioinduction observed in these transformations is presented.
\r\n\r\nThe asymmetric intramolecular allene/enoate [2+2]-photocycloaddition was applied\r\nto the synthesis of the topoisomerase I inhibitor chebulagic acid. The synthetic utility of\r\nthis reaction was demonstrated by the preparation of an advanced intermediate containing\r\nall of the stereochemical information present in the chebulic acid fragment of chebulagic\r\nacid. In the course of these synthetic studies an unusual 8-alkynyl lactone photoproduct\r\nwas obtained upon photocyloaddition of a substrate that was expected to afford a [7.6.6.4]tetracyclic\r\nsystem. A 1,5-hydrogen shift in a biradical intermediate was implicated in the\r\nformation of this product by isotopic labeling studies; the mechanistic implications of these\r\nresults for enantioselectivity in photochemical reactions of optically active allenes tethered\r\nto enones and enoates are discussed.
\r\n\r\nPart B. The DNA recognition properties of peptide conjugates of\r\nphenenthrenequinone diimine complexes of rhodium(III) have been studied. The structural\r\nand thermodynamic basis for the 5'-CCA-3'-selectivity of the metallointercalator-peptide\r\nconjugate [Rh(phi)2(phen')]3+ -AANVAIAAWERAA-CONH2 was investigated. A protocol\r\nfor measuring dissociation constants of DNA cleaving ligands by cleavage titration is\r\ndescribed. Using this protocol, the energetic contribution of the peptide to sequenceselective\r\nbinding was assessed, and evidence for the origin of the enhanced sequenceselectivity\r\nobserved at elevated temperature was obtained. Micromolar quantities of [\u0394Rh-(phi)2(phen')]3+-AANVAIAAWERAA-CONH2 were synthesized to examine the\r\nstructure of the metallointercalator-peptide conjugate and the metallointercalator-peptide\r\nconjugate\u2022DNA complex by NMR. NMR results for the metallointercalator-peptide\r\nconjugate in the absence of DNA are reported.
\r\n\r\nA family of peptide conjugates of [Rh(phi)2(phen')]3+(phi = 9, 10-\r\nphenanthrenequinone diimine, phen' = 5-(amidoglutaryl)-1,10-phenanthroline) was also\r\nsynthesized. The peptide sequences were obtained by single amino acid modification of the\r\n5'-CCA-3'-selective metallointercalator-peptide conjugate [Rh(phi)2(phen')]3+-\r\nAANVAIAAWERAA-CONH2 to explore the correlation between the amino acid sequence\r\nof the peptide and the nucleotide sequence of the DNA target. Changing the position of the\r\nglutamate at position 10 in the sequence of the appended peptide resulted in the\r\nidentification of a 5'-ACA-3'-selective metallointercalator-peptide conjugate,\r\n[Rh(phi)2(phen')3+-AANVAEAAWARAA-CONH2. Locating the glutamate on one face of\r\na putative \u03b1-helix was found to be essential for sequence specificity; peptide conjugates\r\nwith the glutamate at positions 7, 8, 12, and 13 did not afford sequence-selective DNA\r\nrecognition. Further amino acid substitutions were made at positions 6 and 10. Mutating\r\nthe glutamate at position 6 to arginine caused complex changes in the recognition\r\ncharacteristics of the resulting conjugate. To probe the interactions that give rise to\r\nsequence specificity, we have measured thermodynamic dissociation constants for these\r\nsequence-selective metallointercalator-peptide conjugates and [Rh(phi)2(phen')]3+.
\r\n\r\nThe observed sequence preferences are consistent with the model of Sardesai et al.\r\nfor the sequence selectivity of Rh(phi)2(phen')]3+-AANVAIAAWERAA-CONH2. This\r\nmodel states that sequence-specific DNA recognition requires the peptide to adopt an \u03b1-helical\r\nconformation, and that Glu10 makes a critical base-specific contact with the 5'-\r\nterminal cytosine of the recognition sequence. Using the additional sequence-selectivity\r\ndata, this model is refined. This refined model suggests that recognition of the central C\u2022G\r\nbase pair of the 5'-CCA-3' recognition sequence of [Rh]-E10 is accomplished by Ile6\r\nthrough shape-selection, and that recognition of the 5' -terminal A\u2022T base pair of the 5' -\r\nACA-3' recognition sequence of [Rh]-E6 is accomplished by van der Waals contacts\r\nbetween alanine and thymine methyl groups. The implications of these results for the de\r\nnova design of sequence-selective DNA binding peptides are discussed.
", "doi": "10.7907/e4be-bd57", "publication_date": "1998", "thesis_type": "phd", "thesis_year": "1998" }, { "id": "thesis:17553", "collection": "thesis", "collection_id": "17553", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07232025-205751565", "primary_object_url": { "basename": "Li_RT_1997.pdf", "content": "final", "filesize": 42348655, "license": "other", "mime_type": "application/pdf", "url": "/17553/1/Li_RT_1997.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Development of Late Transition Metal Catalysts for the Transformation of Olefins", "author": [ { "family_name": "Li", "given_name": "Robert Tan", "clpid": "Li-Robert-Tan" } ], "thesis_advisor": [ { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" } ], "thesis_committee": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" }, { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Chapter 1 describes the syntheses and reactivities of a series of\r\nIrCl(CO)(PR3(\u019e2-3,3-diphenylcyclopropene) complexes (PR3 = PMe3, PMe2Ph,\r\nPMePh2, PEt3). In addition, it describes a subsequent reaction of IrCl(CO)(PMe3)2(\u019e2-\r\n3,3-diphenylcyclopropene) in the presence of excess IrCl(CO)(PMe3)2. Spectroscopic\r\ndata support the formation of an iridacyclobutene as part of a bimetallic complex where\r\nthe iridacyclobutene moiety is stabilized by \u019e2-coordination to IrCl(CO)(PMe3)2. The\r\nmechanism of this reaction was studied by kinetic measurements and isotopic labeling\r\nstudies where these studies support formation of this bimetallic complex by direct\r\ninsertion of IrCl(CO)(PMe3)2 into the C-C \u03c3-bond of the cyclopropene moiety.
\r\n\r\nChapter 2 describes the reactions of the iridium dimer, [Ir(COD)Cl]2, with 3,3-\r\ndiphenylcyclopropene to form the bimetallic vinylcarbene complex [Ir(COD)Cl]2=C-C=\r\nCPh2), and examines the activity of this complex in ring-opening metathesis\r\npolymerization (ROMP). This chapter also describes the subsequent reaction of\r\n[Ir(COD)Cl]2(=C-C=CPh2) with AgO2CCX3 (X = F and H) to form\r\n[Ir2(COD)2Cl(O2CX3)](=C-C=CPh2) and describes their reactivity in ROMP.
\r\n\r\nChapter 3 describes the synthesis of Ir and Rh vinylcarbene complexes and examines\r\ntheir activities in olefin metathesis and olefin cyclopropanation. The Ir vinylcarbene\r\nappears to be active solely in olefin metathesis and the Rh vinylcarbene appears to be\r\nactive solely in olefin cyclopropanation. In addition, this chapter investigates the\r\noxidation state effects in the Rh-mediated cyclopropanation reaction by examining the\r\naffinities of the Rh complexes toward olefins as the oxidation state of the Rh metal is\r\nincreased.
\r\n\r\nChapter 4 describes the synthesis of salicylaldimine complexes of Ni(II)-aryls and\r\ntheir reactivity in ethylene polymerization. The effects of varying sterics and electronics\r\nof the salicyclaldimine ligand is discussed. Bulky ligands which block the axial faces of\r\nthe Ni(II) square planar complexes, and provide steric bulk in the plane of the Ni(II)\r\nsquare planar complex, are particularly effective in providing active ethylene\r\npolymerization catalysts that produce linear polymers with high molecular weight.
", "doi": "10.7907/h7n7-w490", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:10841", "collection": "thesis", "collection_id": "10841", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05012018-081029790", "primary_object_url": { "basename": "STAHL_SS_1997.pdf", "content": "final", "filesize": 50839058, "license": "other", "mime_type": "application/pdf", "url": "/10841/1/STAHL_SS_1997.pdf", "version": "v4.0.0" }, "type": "thesis", "title": "Mechanistic Studies of Alkane Activation by Platinum(II) Complexes", "author": [ { "family_name": "Stahl", "given_name": "Shannon Scot", "orcid": "0000-0002-9000-7665", "clpid": "Stahl-Shannon-Scot" } ], "thesis_advisor": [ { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" } ], "thesis_committee": [ { "family_name": "Gray", "given_name": "Harry B.", "clpid": "Gray-H-B" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" }, { "family_name": "Carreira", "given_name": "Erick Moran", "clpid": "Carreira-E-M" }, { "family_name": "Labinger", "given_name": "Jay A.", "clpid": "Labinger-J-A" }, { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Currently, there is considerable interest in alkane oxidation reactions catalyzed by transition metal complexes. Chapter 1 reviews many of the recent advances in this field involving electrophilic late transition metals. The C-H activation step appears to dictate both the rate and selectivity of these reactions. Unfortunately, however, very little is known about the mechanism of this step.
\r\n\r\nIn chapter 2, mechanistic studies of the protonolysis of several alkylplatinum(II) complexes [(tmeda)PtMeCl, (tmeda)Pt(CH2Ph)Cl, (tmeda)PtMe2, and trans(PEt3)2Pt(CH3)Cl] are described. These reactions model the microscopic reverse of C-H activation by aqueous Pt(II). Kinetics, activation parameters, and isotope effects were determined, and the results support a common mechanistic sequence for all of the reactions: (1) chloride- or solvent-mediated protonation of Pt(II) to generate an alkylhydridoplatinum(IV) intermediate, (2) dissociation of solvent or chloride to generate a cationic, five-coordinate platinum(IV) species, (3) reductive C-H bond formation producing a platinum(II) alkane \u03c3-complex, and (4) loss of alkane either through an associative or dissociative substitution pathway. These studies provide insight into the role of solvent and ancillary ligands in aqueous Pt(II)-mediated C-H activation. The results also support the viability of Pt(II) \u03c3-adducts and alkylhydridoplatinum(IV) intermediates in this reaction.
\r\n\r\nChapter 3 describes the preparation and study of Pt(II) H2-adducts and Pt(IV) dihydride complexes. The species of interest are generated by protonation of hydridoplatinum(II) complexes of the type trans-(PCy3)2Pt(H)X [X = SiH3, H, CH3, Ph, Cl, Br, I, CN, CF3SO3] and [trans-(PCy3)2Pt(H)L][Barf4] [L = CO, 4-picoline; Barf4] = B(3,5-C6H3(CF3)2)4]. The proton attacks one of three different sites on these complexes (hydride, platinum, or the trans ligand), depending on which ligand is trans to hydride. These studies reveal several factors affecting the stability and reactivity of Pt(II) \u03c3-adducts, which thus have implications for C-H activation by Pt(II).
\r\n", "doi": "10.7907/CCAZ-9234", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:8089", "collection": "thesis", "collection_id": "8089", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:02202014-095838875", "primary_object_url": { "basename": "Yang-bh-1997.pdf", "content": "final", "filesize": 35168728, "license": "other", "mime_type": "application/pdf", "url": "/8089/1/Yang-bh-1997.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Use of pseudoephedrine as a practical chiral auxiliary for asymmetric synthesis", "author": [ { "family_name": "Yang", "given_name": "Bryant H.", "clpid": "Yang-Bryant-H" } ], "thesis_advisor": [ { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" } ], "thesis_committee": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" }, { "family_name": "Carreira", "given_name": "Erick Moran", "clpid": "Carreira-E-M" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "clpid": "Barton-J-K" }, { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "The use of pseudoephedrine as a practical chiral auxiliary for asymmetric synthesis is describe. Both enantiomers of pseudoephedrine are inexpensive commodity chemicals and can be N-acylated in high yields to form tertiary amides. In the presence of lithium chloride, the enolates of the corresponding pseudoephedrine amides undergo highly diastereoselective a1kylations with a wide range of alkyl halides to afford \u03b1-substituted products in high yields. These products can then be transformed in a single operation into highly enantiomerically enriched carboxylic acids, alcohols, and aldehydes. Lithium amidotrihydroborate (LAB) is shown to be a powerful reductant for the selective reduction of tertiary amides in general and pseudoephedrine amides in particular to form primary alcohols.
\t\r\n", "doi": "10.7907/1K2S-P110", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:17534", "collection": "thesis", "collection_id": "17534", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07162025-181821401", "primary_object_url": { "basename": "Singer_RA_1997.pdf", "content": "final", "filesize": 55951942, "license": "other", "mime_type": "application/pdf", "url": "/17534/1/Singer_RA_1997.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Design of Novel Titanium(IV) Schiff Base Complexes for Catalytic, Enantioselective Aldol Additions to Aldehydes", "author": [ { "family_name": "Singer", "given_name": "Robert Alan", "orcid": "0000-0001-9730-1261", "clpid": "Singer-Robert-Alan" } ], "thesis_advisor": [ { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" } ], "thesis_committee": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "orcid": "0000-0003-1464-2461", "clpid": "Dougherty-D-A" }, { "family_name": "Barton", "given_name": "Jacqueline K.", "orcid": "0000-0001-9883-1600", "clpid": "Barton-J-K" }, { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" }, { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "A novel chiral Schiff base ligand derived from 2-amino-2'-hydroxy-1, 1'-binaphthyl\r\nand 3-bromo-5-tbutylsalicylaldehyde has been prepared. When binding the chiral ligand to\r\ntitanium(IV) with 3,5-di-fbutylsalicylic acid, the complex formed functions as an efficient\r\ncatalyst for the Mukaiyama aldol addition reaction. Using only 1-2 mol% of the catalyst,\r\nsilyl ketene acetal additions to aldehydes were carried out in good chemical yield and in\r\nexcellent levels of enantioselectivity. Unsaturated aldehydes tended to produce adducts in\r\n95-99% ee, while aliphatic aldehyde products were typically obtained in 94-95% ee.
\r\n\r\nThe methodology was extended to include dienolate additions to aldehydes by\r\nutilizing silyl enol ethers of dioxinones. Optimal selectivities in the dienolate additions\r\nwere obtained with unsaturated, unbranched aldehydes (90-94% ee). Aromatic and\r\naliphatic aldehydes were usually isolated in 80-84% ee. Since many of the adducts were\r\ncrystalline solids, the optical purity was enhanced by recrystallization. By heating the\r\ndioxinone adduct in the presence of an alcohol or amine, the products were transformed to\r\nmore useful \u03b2-ketoesters or \u03b2-ketoamides.
\r\n\r\nTo demonstrate the utility of the methodology developed, the asymmetric addition\r\nreactions have been applied to the total synthesis of (R)-epinephrine and macrolactin A.\r\nAfter carrying out an enantioselective acetate addition to 3,4-dimethoxybenzaldehyde in\r\n95% ee, the \u03b2-hydroxyester was converted to the amino-alcohol by a Hoffman\r\nrearrangement and a reduction. After deprotecting the catechol, (R)-epinephrine was\r\nobtained in 5 steps overall. Dienolate additions to \u03b2-stannylpropenal were employed to\r\nprepare two key fragments of macrolactin A. The convergent route involved stitching\r\ntogether three fragments with a Stille coupling and a Horner-Emmons olefination.\r\nMacrocyclization was accomplished by an intramolecular Stille coupling.
", "doi": "10.7907/w287-z238", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:17553", "collection": "thesis", "collection_id": "17553", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:07232025-205751565", "primary_object_url": { "basename": "Li_RT_1997.pdf", "content": "final", "filesize": 42348655, "license": "other", "mime_type": "application/pdf", "url": "/17553/1/Li_RT_1997.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Development of Late Transition Metal Catalysts for the Transformation of Olefins", "author": [ { "family_name": "Li", "given_name": "Robert Tan", "clpid": "Li-Robert-Tan" } ], "thesis_advisor": [ { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" } ], "thesis_committee": [ { "family_name": "Gray", "given_name": "Harry B.", "orcid": "0000-0002-7937-7876", "clpid": "Gray-H-B" }, { "family_name": "Grubbs", "given_name": "Robert H.", "orcid": "0000-0002-0057-7817", "clpid": "Grubbs-R-H" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" }, { "family_name": "Carreira", "given_name": "Erick Moran", "orcid": "0000-0003-1472-490X", "clpid": "Carreira-E-M" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Chapter 1 describes the syntheses and reactivities of a series of\r\nIrCl(CO)(PR3(\u019e2-3,3-diphenylcyclopropene) complexes (PR3 = PMe3, PMe2Ph,\r\nPMePh2, PEt3). In addition, it describes a subsequent reaction of IrCl(CO)(PMe3)2(\u019e2-\r\n3,3-diphenylcyclopropene) in the presence of excess IrCl(CO)(PMe3)2. Spectroscopic\r\ndata support the formation of an iridacyclobutene as part of a bimetallic complex where\r\nthe iridacyclobutene moiety is stabilized by \u019e2-coordination to IrCl(CO)(PMe3)2. The\r\nmechanism of this reaction was studied by kinetic measurements and isotopic labeling\r\nstudies where these studies support formation of this bimetallic complex by direct\r\ninsertion of IrCl(CO)(PMe3)2 into the C-C \u03c3-bond of the cyclopropene moiety.
\r\n\r\nChapter 2 describes the reactions of the iridium dimer, [Ir(COD)Cl]2, with 3,3-\r\ndiphenylcyclopropene to form the bimetallic vinylcarbene complex [Ir(COD)Cl]2=C-C=\r\nCPh2), and examines the activity of this complex in ring-opening metathesis\r\npolymerization (ROMP). This chapter also describes the subsequent reaction of\r\n[Ir(COD)Cl]2(=C-C=CPh2) with AgO2CCX3 (X = F and H) to form\r\n[Ir2(COD)2Cl(O2CX3)](=C-C=CPh2) and describes their reactivity in ROMP.
\r\n\r\nChapter 3 describes the synthesis of Ir and Rh vinylcarbene complexes and examines\r\ntheir activities in olefin metathesis and olefin cyclopropanation. The Ir vinylcarbene\r\nappears to be active solely in olefin metathesis and the Rh vinylcarbene appears to be\r\nactive solely in olefin cyclopropanation. In addition, this chapter investigates the\r\noxidation state effects in the Rh-mediated cyclopropanation reaction by examining the\r\naffinities of the Rh complexes toward olefins as the oxidation state of the Rh metal is\r\nincreased.
\r\n\r\nChapter 4 describes the synthesis of salicylaldimine complexes of Ni(II)-aryls and\r\ntheir reactivity in ethylene polymerization. The effects of varying sterics and electronics\r\nof the salicyclaldimine ligand is discussed. Bulky ligands which block the axial faces of\r\nthe Ni(II) square planar complexes, and provide steric bulk in the plane of the Ni(II)\r\nsquare planar complex, are particularly effective in providing active ethylene\r\npolymerization catalysts that produce linear polymers with high molecular weight.
", "doi": "10.7907/h7n7-w490", "publication_date": "1997", "thesis_type": "phd", "thesis_year": "1997" }, { "id": "thesis:14038", "collection": "thesis", "collection_id": "14038", "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:12222020-002250563", "primary_object_url": { "basename": "colocci-n_1996.pdf", "content": "final", "filesize": 65451588, "license": "other", "mime_type": "application/pdf", "url": "/14038/1/colocci-n_1996.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "Cooperative Oligonucleotide-Directed Triple Helix Formation at Adjacent DNA Sites", "author": [ { "family_name": "Colocci", "given_name": "Natalia", "clpid": "Colocci-Natalia" } ], "thesis_advisor": [ { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" } ], "thesis_committee": [ { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" }, { "family_name": "Carreira", "given_name": "Erick Moran", "clpid": "Carreira-E-M" }, { "family_name": "Dervan", "given_name": "Peter B.", "clpid": "Dervan-P-B" }, { "family_name": "Goddard", "given_name": "William A., III", "clpid": "Goddard-W-A-III" }, { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Cooperative interactions between DNA-binding ligands are essential for their sequence specificity, binding affinity, and biological activity. Oligonucleotides can bind cooperatively to adjacent sites on double-helical DNA by triple helix formation. The study of the cooperative binding of oligonucleotides to DNA by triple helix formation is important as it provides useful information for the development of new methods leading to the sequence-specific recognition of DNA. As a first step towards this goal, the thermodynamics of the cooperative binding of oligodeoxyribonucleotides to adjacent DNA sites by triple helix formation have been determined by quantitative affinity cleavage titrations (Chapter Two). A 20-fold enhancement in equilibrium association constant is realized for an 11mer pyrimidine oligonucleotide binding in the presence of a neighboring bound site at 24 \u00b0C and pH 7.0 (25 mM TrisOAc, 10 mM NaCl, 1 mM spermine). This corresponds to an increase in binding free energy of 1.8 kcal\u2022mol\u207b\u00b9. This cooperativity is not observed when the two binding sites are separated by one base pair. The observed cooperative energy likely arises from favorable polarization and charge-charge interactions between the terminal bases at the triple-helical junction.
\r\n\r\nIn addition, the energetics of cooperative binding by oligodeoxyribonucleotides to adjacent sites by triple helix formation have been determined as a function of sequence composition at the junction (Chapter Three). The binding affinity of an 11mer in the presence of a neighboring bound oligonucleotide is enhanced by a factor of 12, 17, 61, and 127 when a 5'-TT-3', 5'-\u1d50C\u1d50C-3', 5'-T\u1d50C-3', and 5'-\u1d50CT-3' stack, respectively, is formed at the junction (10 mM Bis-Tris\u2022HCl at pH 7.0, 10 mM NaCl, 250 \u00b5M spermine, 24 \u00b0C) (\u1d50C designates 5-methyl-2'-deoxycytidine). These binding enhancements correspond to an interaction energy between the two oligonucleotides of 1.5, 1.7, 2.5, and 2.9 kcal\u2022mol\u207b\u00b9, respectively. The energetic penalties for a single-base mismatch differ depending on sequence and the location of the mismatch with respect to the 5'- or 3'-side of the junction. In the case of a 5'-TT-3' stack, a T\u2022GC mismatch on the 5'- side of the junction decreases the interaction energy from 1.5 kcal\u2022mol\u207b\u00b9 to 0.6 kcal\u2022mol\u207b\u00b9, whereas a T\u2022GC mismatch on the 3'- side destroys cooperativity. For a 5'-\u1d50CT-3' stack, a \u1d50C\u2022AT mismatch on the 5'-side of the junction decreases the cooperative interaction energy from 2.9 kcal\u2022mol\u207b\u00b9 to 1.7 kcal\u2022mol\u207b\u00b9, whereas a T\u2022GC mismatch on the 3'-side of the junction destroys cooperativity. Most importantly, two 11mer oligonucleotides interacting through a 5'-TT -3' stack binding to adjacent sites on DNA are significantly more sensitive to single-base mismatches than the corresponding 22mer binding to the same two abutting sites.
\r\n\r\nThe use of modified bases, such as 5-(1-propynyl)-2'-deoxyuridine, increases cooperativity between oligonucleotides bound to adjacent sites on DNA, presumably due to an increased stacking energy between the modified bases at the triplex junction (Chapter Four). Oligodeoxyribonucleotides containing 5-(1-propynyl)-2'-deoxyuridine and 5-methyl-2'-deoxycytidine as short as 8 nucleotides in length bind at micromolar concentrations to adjacent 8-bp sites on double-helical DNA at 24 \u00b0C and pH 7.0 (10 mM Bis-Tris\u2022HCl, 10 mM NaCl, 1 mM spermine). Quantitative affinity cleavage titrations reveal that the binding affinity of an 8mer in the presence of a neighboring bound 8mer is enhanced by a factor of at least 40. This corresponds to a remarkable cooperative interaction energy of > 4.5 kcal\u2022mol\u207b\u00b9. In addition, these cooperative interactions allow oligonucleotides as short as 6mers to bind to three adjacent sites on double-helical DNA at near micromolar concentrations (10 mM Bis-Tris\u2022HCl at pH 7.0, 10 mM NaCl, 1 mM spermine, 24 \u00b0C).
\r\n\r\nCooperativity is also observed between purine-rich oligonucleotides (Chapter Five). Quantitative DNase footprinting titration experiments show that the binding affinity of an 11mer purine-rich oligonucleotide in the presence of a neighboring bound oligonucleotide is enhanced by a factor of 81 when a 5'-GG-3' stack is formed at the junction (50 mM TrisOAc at pH 7.0, 10 mM NaCl, 10 mM MgCl\u2082, 24 \u00b0C). This binding enhancement corresponds to an interaction energy between the two oligonucleotides of 2.7 kcal\u2022mol\u207b\u00b9, and is abolished when the two binding sites are separated by one base pair.
\r\n\r\nThe synthesis of pyrimidine oligonucleotide analogs containing 5-(1-propynyl)- and 2'-O-allyl-modified nucleosides (Chapter Six), and the progress towards the synthesis of a novel base, N7-2'-deoxyisoinosine, designed for the recognition of AT base pairs within a parallel isomorphous purine motif (Chapter Seven), are described.
", "doi": "10.7907/08j6-sd37", "publication_date": "1996", "thesis_type": "phd", "thesis_year": "1996" }, { "id": "thesis:3870", "collection": "thesis", "collection_id": "3870", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-10022007-135120", "primary_object_url": { "basename": "Fraley_me_1995.pdf", "content": "final", "filesize": 10245672, "license": "other", "mime_type": "application/pdf", "url": "/3870/1/Fraley_me_1995.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Synthesis of (+)-dynemicin A and analogs of wide structural variability. Establishment of the absolute configuration of natural dynemicin A", "author": [ { "family_name": "Fraley", "given_name": "Mark E.", "clpid": "Fraley-M-E" } ], "thesis_advisor": [ { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" } ], "thesis_committee": [ { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" }, { "family_name": "Dougherty", "given_name": "Dennis A.", "clpid": "Dougherty-D-A" }, { "family_name": "Carreira", "given_name": "Erick Moran", "clpid": "Carreira-E-M" }, { "family_name": "Dervan", "given_name": "Peter B.", "clpid": "Dervan-P-B" }, { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "A highly convergent synthetic route to the potent natural antitumor agent (+)-dynemicin A (1) is described. Key features of the synthesis include: (1) the condensation of the potassium enolate of menthyl acetoacetate with trans-ethyl crotonate, providing the optically pure trans-disubstituted 1,3-cyclohexanedione 38; (2) the palladium-catalyzed coupling of the enol triflate 37 with t-butyl 2-borono-4-methoxycarbanilate to furnish 35, followed by the thermolysis of the latter to afford the quinolone 34; (3) the stereoselective acetylide addition of the (Z)-enediyne bridge to an acylquinolinium intermediate derived from quinoline 60, affording the addition product 61; (4) the acetylide-mediated closure of the (Z)-enediyne bridge of ketone 65 to produce 66; (5) the carboxylation and subsequent methylation of ketone 69, providing the vinylogous carbonic acid 70; (6) the oxidation of the phenol 73 to furnish the enone 74, as well as the reductive deprotection of 75 to afford the quinone imine 77; and (7) the Diels-Alder cycloaddition reaction of the quinone imine 77 with 1,4,7-tris(trimethylsiloxy)isobenzofuran, followed by the desilylation and oxidation of the resultant adduct to complete the synthesis of 1. The preparation of structurally diverse analogs of 1 by late-stage modification of the synthetic route is detailed. The absolute configuration of natural 1 is determined to be 2S, 3S, 4S, 7R, 8R, by the comparison of circular dichroism spectra of synthetic and authentic 1.\r\n", "doi": "10.7907/7a9e-t435", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" }, { "id": "thesis:3810", "collection": "thesis", "collection_id": "3810", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09282005-160712", "primary_object_url": { "basename": "Nguyen_st_1995.pdf", "content": "final", "filesize": 6632287, "license": "other", "mime_type": "application/pdf", "url": "/3810/1/Nguyen_st_1995.pdf", "version": "v2.0.0" }, "type": "thesis", "title": "The designs, syntheses, and applications of well-defined, single component group VIII olefin metathesis catalysts", "author": [ { "family_name": "Nguyen", "given_name": "SonBinh TheBao", "clpid": "Nguyen-S-T" } ], "thesis_advisor": [ { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" }, { "family_name": "Lewis", "given_name": "Nathan Saul", "clpid": "Lewis-N-S" } ], "thesis_committee": [ { "family_name": "Lewis", "given_name": "Nathan Saul", "clpid": "Lewis-N-S" }, { "family_name": "Grubbs", "given_name": "Robert H.", "clpid": "Grubbs-R-H" }, { "family_name": "Carreira", "given_name": "Erick Moran", "clpid": "Carreira-E-M" }, { "family_name": "Gray", "given_name": "Harry B.", "clpid": "Gray-H-B" }, { "family_name": "Beauchamp", "given_name": "Jesse L.", "clpid": "Beauchamp-J-L" }, { "family_name": "Bercaw", "given_name": "John E.", "clpid": "Bercaw-J-E" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\r\n\r\nThis thesis reports the synthesis and reactivity studies of a series of [...] complexes (X is an anionic ligand, L represents a neutral, two-electron donor ligand, M is either Ru or Os, and CHR represents a carbene moiety). These complexes are olefin metathesis catalysts and is remarkable in their stability toward a variety of functional groups, including protic species such as water and acid.\r\n\r\nChapter 2 describes the synthesis, stability, and mechanism of formation of the forementioned [...] catalysts from a strained 3,3-disubstituted cyclopropene. Their metathesis activities as functions of the anionic ligands and the metal center will be discussed together with the mechanism of cyclopropene-vinylcarbene rearrangement at Group VIII metal centers . In chapter 3 and chapter 4, the modification of the metathesis activity of these catalysts as functions of the ancillary phosphine ligands and the carbene substituents, respectively, will be presented. Chapter 5 describes the applications of this new catalyst system in the self metathesis and ethenolysis of oleic acid and its methyl ester. The acyclic diene metathesis polymerization and polyolefin depolymerization reactions catalyzed by these new catalysts are the subjects of chapter 6. Chapter 7 reports the results of resin-immobilization experiments and Chapter 8 is a collection of the author's personal impressions of the development in this area of chemistry over the last decade.", "doi": "10.7907/1BVB-S189", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" }, { "id": "thesis:1754", "collection": "thesis", "collection_id": "1754", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-05122005-160230", "primary_object_url": { "basename": "Campbell_sa_1995.pdf", "content": "final", "filesize": 7537996, "license": "other", "mime_type": "application/pdf", "url": "/1754/1/Campbell_sa_1995.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "FT-ICR studies of the structures, energetics and reaction dynamics of biological molecules in the gas phase", "author": [ { "family_name": "Campbell", "given_name": "Sherrie A.", "clpid": "Campbell-S-A" } ], "thesis_advisor": [ { "family_name": "Beauchamp", "given_name": "Jesse L.", "clpid": "Beauchamp-J-L" } ], "thesis_committee": [ { "family_name": "Beauchamp", "given_name": "Jesse L.", "clpid": "Beauchamp-J-L" }, { "family_name": "Zewail", "given_name": "Ahmed H.", "clpid": "Zewail-A-H" }, { "family_name": "Carreira", "given_name": "Erick Moran", "clpid": "Carreira-E-M" }, { "family_name": "Dervan", "given_name": "Peter B.", "clpid": "Dervan-P-B" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "Fourier transform ion cyclotron resonance (FT-ICR) mass spectroscopy has been used to investigate the energetics and reaction dynamics of biological molecules in the gas phase. Experimental results aid in predicting gas phase protonation sites and molecular conformations of peptides and amino acids. Correlations of proton affinities with adiabatic lone-pair ionization energies indicate that amino acids lacking basic side chains protonate on the amine nitrogen, while more basic amino acids protonate on their side chain. These results have been similarly applied to small peptides, with protonation predicted on the N-terminus for peptides lacking basic amino acid residues.\n\nTwo novel experimental methods have been developed for measuring gas phase proton affinities, which utilize infrared multiphoton dissociation and collision induced dissociation techniques to cleave proton-bound dimers of reagent gases. The dimers fragment into two products with the more basic reagent retaining the proton. A simplified RRKM analysis is used to determine proton affinities from product ion abundances.\n\nIsotopic hydrogen exchange reactions of protonated glycine oligomers with a series of reagent bases have been performed, and the exchange mechanisms and energetics identified. Although it is not the sole determining factor, the extent and rates of H/D exchange increase with reagent basicity, with ND3 being the most efficient exchange gas studied. Exchange of the N-terminus hydrogens occurs via an onium ion mechanism in which an endothermic proton transfer is rendered energetically favorable by simultaneous solvation of the ammonium ion. Exchange of the C-terminus occurs via a salt bridge intermediate, in which the carboxylate and ammonium ion is stabilized by interactions with the nearby protonated N-terminus.\n\nFinally, the H/D exchange reactions of several peptides possessing basic residues with ND3 have been investigated. The results indicate that basic amino acids hinder exchange processes as protonation energetics and molecular folding become more important. Calculations using semiempirical AM1 and PM3 methods were performed to identify the gas phase configurations of the protonated peptides and determine if stable salt bridge structures are possible. Potential energy surfaces were also calculated for all exchange processes.\n", "doi": "10.7907/z6t6-nz51", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" }, { "id": "thesis:3628", "collection": "thesis", "collection_id": "3628", "cite_using_url": "https://resolver.caltech.edu/CaltechETD:etd-09182007-090157", "primary_object_url": { "basename": "Cohen_sb_1995.pdf", "content": "final", "filesize": 7121593, "license": "other", "mime_type": "application/pdf", "url": "/3628/1/Cohen_sb_1995.pdf", "version": "v3.0.0" }, "type": "thesis", "title": "Mechanistic studies of the natural DNA-cleaving agents neocarzinostatin chromophore, calicheamicin [gamma]1, and dynemicin A", "author": [ { "family_name": "Cohen", "given_name": "Scott B.", "clpid": "Cohen-S-B" } ], "thesis_advisor": [ { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" } ], "thesis_committee": [ { "family_name": "Myers", "given_name": "Andrew G.", "clpid": "Myers-A-G" }, { "family_name": "Rees", "given_name": "Douglas C.", "clpid": "Rees-D-C" }, { "family_name": "Carreira", "given_name": "Erick Moran", "clpid": "Carreira-E-M" }, { "family_name": "Dervan", "given_name": "Peter B.", "clpid": "Dervan-P-B" } ], "local_group": [ { "literal": "div_chem" } ], "abstract": "NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document.\r\n\r\nExperiments establishing the intermediacy of the cumulene derived from neocarzinostatin chromophore are described. It is shown that [...]95% of DNA cleavage arises via the cumulene. The sequence specificity and efficiency of DNA cleavage by externally generated cumulene are identical to that by the cumulene formed in situ, supporting the proposal that the cumulene determines the sequence specificity of DNA cleavage. It is shown that DNA and a water-soluble cyclohexadiene derivative are equally effective in trapping of the biradical intermediate at concentrations of 5 mM and 1 M, respectively, supporting the idea that the biradical must be generated as a DNA-bound species to induce DNA cleavage.\r\n\r\nThe reaction of calicheamicin [...] with glutathione has been studied in the presence of DNA and is shown to produce all four products arising from S-S bond exchange. The calicheamicin-glutathione disulfide is formed as the major product of this reaction, and is shown to be 2-3 orders of magnitude less reactive toward glutathione than is calicheamicin [...]. The rate of DNA cleavage by calicheamicin [...] is essentially independent of the concentration of DNA, while the rate of DNA cleavage by the calicheamicin-glutathione disulfide is inversely proportional to the concentration of DNA. The data support the hypothesis that calicheamicin [...] undergoes thiol activation as a DNA-bound species, while the calicheamicin-glutathione disulfide is activated free in solution.\r\n\r\nBinding constants of dynemicin A and synthetic analogs to DNA show that the two E-ring hydroxyls of the anthraquinone contribute approximately 2.7 kcal/mol binding energy, and that neutralization of the negatively-charged carboxylate stabilizes the drug DNA binding complex by ~3 kcal/mol. Dynemicin A and the synthetic analogs display an inverse rate dependence on the concentration of DNA, supporting the proposal that these drugs must dissociate from DNA prior to chemical activation.\r\n", "doi": "10.7907/ZJH6-AC74", "publication_date": "1995", "thesis_type": "phd", "thesis_year": "1995" } ]