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Progress toward the total synthesis of citrinadins A and B

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dc.contributor.authorSmith, Genessa M., author
dc.contributor.authorWood, John L., advisor
dc.contributor.authorWilliams, Robert M., committee member
dc.contributor.authorFerreira, Eric M., committee member
dc.contributor.authorChen, Eugene Y., committee member
dc.contributor.authorO'Keefe, Garrett J., committee member
dc.date.accessioned2007-01-03T08:10:14Z
dc.date.available2007-01-03T08:10:14Z
dc.date.issued2012
dc.description.abstractIn 2005 Kobayashi reported the isolation and absolute stereochemistry of Citrinadin A (1) and Citrinadin B (2), novel secondary metabolites of the marine fungus Penicillium citrinum. In addition to their interesting molecular architecture, the citrinadins are biologically active. Both exhibit cytotoxicity against murine leukemia L1210 (IC50 6.2 and 10 μg/mL respectively), and 1 has shown activity against human epidermoid carcinoma KB cells (IC50 6.2 μg/mL). Synthesis of 1 and 2 would allow for further testing of their biological activity and remains the best way to confirm their assigned structures. While, no total synthesis of either natural product has been reported to date, two synthetic approaches toward the citrinadins have been disclosed by Martin and Sorensen. Efforts to synthesize 1 and 2 in the Wood laboratory are based upon a convergent (3+2) dipolar cycloaddition reaction between a spiro-oxindole dipolarophile and a nitrone, where two diastereomeric isoxazolidine cycloadducts are formed. Using the undesired cycloadduct, exploratory studies toward a synthesis of 2 were conducted, resulting in the synthesis of the C3-epi-Citrinadin Core (±)-96. Elaboration of the desired cycloadduct then led to a synthesis of the ent-Citrinadin Core (+)-100. In order gain to access 2, a C7-functionalized spiro-oxindole dipolarophile was employed in the cycloaddition; however, elaboration of the desired C7-functionalized cycloadduct to ent-2 may result in a structural reassignment of 2. Preliminary results suggest that spectral data for the C21-epi-ent diastereomer of 2 (175) match the data reported by Kobayashi for Citrinadin B (2) itself. In an effort to gain access to 1, a (3+2) cycloaddition strategy utilizing a C14-functionalized nitrone was explored. Following the synthesis of three nitrone precursors, a one-pot nitrone formation / (3+2) cycloaddition reaction was developed and one of the cycloadducts was successfully advanced to a key ring-fusion epoxide. Elaboration of this advanced intermediate is expected to eventually provide a total synthesis of Citrinadin A (1).
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierSmith_colostate_0053A_11057.pdf
dc.identifierETDF2012400276CHEM
dc.identifier.urihttp://hdl.handle.net/10217/67651
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subject(3+2) dipolar cycloaddition
dc.subjectnitrone
dc.subjectCitrinadin B
dc.subjectCitrinadin A
dc.titleProgress toward the total synthesis of citrinadins A and B
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineChemistry
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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