Synthesis of Cryptophycins via an N-Acyl-β-lactam Macrolactonization

Ramdas Vidya, Mari Jean Eggen, Sajiv K. Nair, Gunda I. Georg, Richard H. Himes

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

An efficient and concise approach to the synthesis of the macrolide core of the cryptophycins has been developed. A novel macrolactonization utilizing a reactive acyl-β-lactam intermediate incorporates the β-amino acid moiety within the 16-membered macrolide core. This modular approach, involving a cyanide-initiated acyl-β-lactam ring opening followed by cyclization, was successfully applied to the total synthesis of cryptophycin-24. The strategy was also used in an efficient synthesis of the 6, 6-dimethyl-substituted dechlorocryptophycin-52. In this case, the cyanide-initiated ring opening of the bis-substituted 2-azetidinone followed by macrolactonization was achieved through a catalytic process.

Original languageEnglish (US)
Pages (from-to)9687-9693
Number of pages7
JournalJournal of Organic Chemistry
Volume68
Issue number25
DOIs
StatePublished - Dec 12 2003

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