CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

In conclusion, an efficient asymmetric synthesis of the octadienoic acid unit (unit-
A) of cryptophycins was demonstrated from the easily available aldehyde 1. Most of the
existing synthetic routes for unit-A involved several reagents, which were to be prepared
separately and/ or suitable for a very small scale synthesis. In comparison, all the steps in
our synthesis could be carried out conveniently in multi-gram scales. Admittedly, the
intermediates, 132 and 138 were prepared through a circuitous route. However, the target
compound was obtained in an acceptable overall yield (11%). The synthetic strategy was
based on a Ga-mediated highly diastereoselective crotylation of the easily available
aldehyde 1 in [bmim][Br] as one of the key steps. The route provided an efficient
alternative method for installing the cryptophycin epoxide moiety, circumventing the
commonly employed last-step epoxidation, which exhibited poor diastereoselectivity. The
present synthetic route is easily amenable to the synthesis of other members of the
cryptophycin family.
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