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 language | English (US) |
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Pages (from-to) | 9687-9693 |
Number of pages | 7 |
Journal | Journal of Organic Chemistry |
Volume | 68 |
Issue number | 25 |
DOIs | |
State | Published - Dec 12 2003 |