Progress towards the total synthesis of aetheramide A
Abstract
Our efforts toward the total synthesis of aetheramide A have been described. The first strategy involves the synthesis of MEM-protected aetheramide A starting from ethyl cinammate using Sharpless dihydroxylation to install chiral dihydroxy centers, Wittig olefination, asymmetric allylation to install the desired stereochemistry at C26, Evans syn-aldol and cycloamidation as key strategies. By our modified strategy we are able to synthesize C17 epimers of aetheramide A from propane-1,3-diol via Wittig olefination, asymmetric allylation, B-Alkyl Suzuki-Miyuara coupling, Evans syn-aldol, β-elimination of tosylate, and Grubbs-RCM as key strategies. A series of novel HIV-1 protease inhibitors were synthesized featuring chromanes as P2 ligands. The chromanes were synthesized in an optically active manner by utilizing CBS reduction as the key step. Enzymatic evaluation of these inhibitors revealed the most potent compound in the series to be a ligand with a carboxylic acid at the 4-position. The potent compound was co-crystallized with HIV-1 protease enzyme, which revealed a novel hydrogen bonding interaction in the flap region with Gly 48.
Degree
Ph.D.
Advisors
Ghosh, Purdue University.
Subject Area
Organic chemistry
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