Asymmetric Michael Additions of Lithium Propionate Enolates to α,β-Unsaturated Esters: A Study Towards the Total Synthesis of Lonomycin A

• Other Authors: Jo, Sunjin, 1975- (authoraut)
• Format: Others
• Language: English; English
• Published: Florida State University
• Subjects: Biochemistry; Biophysics; Molecular biology; Chemistry
• Online Access: http://purl.flvc.org/fsu/fd/FSU_migr_etd-3505

The Michael addition of lithium enolates to α,β unsaturated esters is considered to be one of the powerful and widely used C-C bond forming methods in organic synthesis. We investigated the Michael addition of lithium propionate enolates using the various chiral auxiliaries to α,β unsaturated esters, methyl 2-bromo-3-methoxy acrylate and dioxinones. Various chiral propionates were prepared from the optically pure and commercially available terpenes in several steps. Michael additions using the chiral auxiliary introduced moderate to high stereoselectivities, and the factors that influence the stereoselection were examined. These results are consistent with a chelated transition state. The stereochemistry of Michael adducts was determined by the Mosher's esterification and NMR experiments. Lonomycin A, which was isolated from Streptomyces ribosidificus in 1975, is a polycyclic ether constituted of six highly functionalized rings and 23 stereocenters. Our synthetic strategy relying on the asymmetric Michael addition of lithium propionate enolate to α,β unsaturated esters introduced stereoselectively the contiguous and alternating methyl and methoxy moieties. This attractive methodology gave an easy access to the crucial intermediates in the synthetic approach towards the right-half fragment of Lonomycin A. === A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. === Spring Semester, 2008. === April 8, 2008. === Lonomycin A, Asymmetric, Michael Addition, Synthesis === Includes bibliographical references. === Robert A. Holton, Professor Directing Dissertation; Robert H. Reeves, Outside Committee Member; Marie E. Krafft, Committee Member; Armen Zakarian, Committee Member; Michael Blaber, Committee Member.