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dc.contributor.advisorMohammad Movassaghi.en_US
dc.contributor.authorPompeo, Matthew M.en_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Chemistry.en_US
dc.date.accessioned2019-10-04T21:35:31Z
dc.date.available2019-10-04T21:35:31Z
dc.date.copyright2019en_US
dc.date.issued2019en_US
dc.identifier.urihttps://hdl.handle.net/1721.1/122452
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2019en_US
dc.descriptionVita. Cataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractI. Convergent and Biomimetic Enantioselective Total Synthesis of (-)-Communesin F Enabled by Diazene-Directed Fragment Assembly. The first biomimetic enantioselective total synthesis of (-)-communesin F based on a late-stage heterodimerization and aminal exchange is described. Our synthesis features the expedient diazene-directed assembly of two advanced fragments to secure the congested C3a-C3a' linkage in three steps, followed by a highly efficient biogenetically inspired aminal reorganization to access the heptacyclic communesin core in only two additional steps. Enantioselective syntheses of the two fragments were developed, with highlights including the catalytic asymmetric halocyclization of tryptamine derivatives, a stereoselective sulfinimine allylation, and an efficient cyclotryptamine-C3a-sulfamate synthesis by either a new silver-promoted nucleophilic amination or a rhodium-catalyzed C-H amination protocol.en_US
dc.description.abstractThe versatile synthesis of the fragments, their stereocontrolled assembly, and the efficient aminal-exchange as supported by in situ monitoring experiments, in addition to the final stage Nl'-acylation of the communesin core provide a highly convergent synthesis of (-)-communesin F. II. Enantioselective Total Synthesis and Anticancer Activity of All Known Communesin Alkaloids and Related Complex Derivatives. A unified enantioselective total synthesis and side-by-side anticancer evaluation of all known epoxide-containing communesin alkaloids and related complex derivatives is described. Our synthesis is predicated on the convergent and modular diazene-directed assembly of two advanced fragments to secure the critical C3a-C3a' linkage followed by a guided biomimetic aminal reorganization to deliver the heptacyclic core of these alkaloids.en_US
dc.description.abstractConcise enantioselective syntheses of the fragments were devised, with highlights including the use of a new, rationallydesigned sulfinamide chiral auxiliary and a highly efficient 1,1,1 -trifluoroacetone-mediated epoxidation. The modularity of our convergent approach enables the rapid synthesis of all epoxidecontaining members of the communesin family from a common synthetic intermediate, which prompted the stereochemical revision of (-)-communesin I, the most recently isolated communesin analogue. Furthermore, the generality of our biomimetic reorganization was conclusively demonstrated in the first total synthesis of an iso-communesin derivative, an unnatural constitutional isomer of the communesin skeleton. Finally, we report the first comparative analysis of the anticancer activities of all naturally occurring communesin alkaloids and nine complex derivatives against five human cancer cell lines.en_US
dc.description.abstractFrom these data, we have identified (-)- communesin B as the most potent natural isolate and discovered that derivatives with N8'- sulfonamide substitution exhibit up to a ten-fold increase in potency over the natural products.en_US
dc.description.statementofresponsibilityby Matthew M. Pompeo.en_US
dc.format.extent506 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectChemistry.en_US
dc.titleTotal synthesis and anticancer evaluation of all known communesin alkaloids and related complex derivativesen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.identifier.oclc1121042946en_US
dc.description.collectionPh.D. Massachusetts Institute of Technology, Department of Chemistryen_US
dspace.imported2019-10-04T21:35:31Zen_US
mit.thesis.degreeDoctoralen_US
mit.thesis.departmentChemen_US


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