Total synthesis of microcolin B, a potent new immunosuppressant
Abstract
Microcolin B, a potent new immunosuppressant isolated from blue-green alga Lyngbya majuscula, has been made using a methyl-controlled asymmetric hydrogenation reaction with rhodium on alumina catalyst on lactone 1.25 for the synthesis of the key (R,R)-2,4-dimethyloctanoic acid 1.1. A new, direct mixed imide formation reaction using pentafluorophenyl ester was also developed for the production of the unusual prolylpyrrolinone 1.2 of microcolin. The pentafluorophenyl ester of Cbz-proline 1.69 was reacted with the lithium imidate of lactam 1.67, providing the mixed imide in 80% yield. Coupling of acid 1.1 with N-terminus of the tripeptide, followed by coupling with prolylpyrrolinone 1.2, gave microcolin B. The new mixed-imide forming reaction was also applied to a formal total synthesis of microcolin A (CHAPTER TWO) and was extended to the synthesis of acyclic mixed imides (CHAPTER THREE).
Degree
Ph.D.
Advisors
Andrus, Purdue University.
Subject Area
Organic chemistry|Microbiology|Pharmacology
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