The effects of N-methylation on the enantioselectivity of catalysis by cyclo[(S)-His-(S)-Phe] and synthesis of the unnatural amino acid (2R, 3R, 4S)-4-amino-7-guanidino-2,3-dihydroxyheptanoic acid (AGDHE), a constituent of the cyclic depsipeptide callipeltin A and investigation of the importance of conjugation in a novel eneyne -allene cyclization
Abstract
Chapter 1 involves the investigation of the stereoselective hydrocyanation of aromatic aldehydes catalyzed by a cyclic dipeptide (cyclo[His-Phe]). This reaction system was known to be complex and believed to involve cooperative interactions of more than one molecule of the catalyst in the reaction mechanism. Through the synthesis and study of methylated analogs of cyclo[His-Phe], this theory was supported and some new insights were gained, even though the exact mechanism remains unknown. Chapter 2 details the synthesis of an unnatural amino acid: (2R, 3R, 4S)-4-amino-7-guanidino-2,3-dihydroxyheptanoic acid (AGDHE). This molecule is a fragment of callipeltin A, a cyclic depsidecapeptide recently isolated from a marine sponge and shown to possess antifungal, anti-HIV, andanti-cancer activity. The synthesis involved stereoselective Horner-Emmans olefination and thorough investigation of dihydroxylation chemistry, as well as significant protecting group manipulation. The target molecule, a protected version of AGDHE, was obtained in 13 steps and 10% overall yield. Chapter 3 describes the synthesis and study of model systems designed to probe novel cyclization reactions previously discovered in this laboratory. The synthesis involved construction of ester and ketone compounds.
Degree
Ph.D.
Advisors
Lipton, Purdue University.
Subject Area
Organic chemistry
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