(2S,1'S,2'R,3'R)-2-(2'-Carboxy-3'-hydroxymethylcyclopropyl) glycine is a highly potent group 2 and 3 metabotropic glutamate receptor agonist with oral activity.

The asymmetric synthesis and biological activity of (2S,1'S,2'R,3'R)-2-(2'-carboxy-3'-hydroxymethylcyclopropyl) glycine ((+)-3) is described. This novel C-3' substituted carboxy cyclopropyl glycine is a highly potent group 2 and group 3 mGluR agonist that has proven to be orally active in both fear potentiated startle (animal model for anxiety) and PCP-induced motor activation (animal model for psychosis) assays in rats.

Synthesis of cryptophycin 52 using the Shi epoxidation.

[reaction: see text] A synthesis of cryptophycin 52 is reported using a Shi epoxidation strategy to install the epoxide moiety in a diastereoselective fashion. Several epoxidation results for cryptophycin substrates are disclosed followed by a discussion of the details relating to the preparation of cryptophycin 52 in two synthetic steps from one of the intermediate epoxides.

Synthesis of Unit A of Cryptophycin via a [2,3]-Wittig Rearrangement.

The synthesis of unit A of the cryptophycins from (S)-trans-3-penten-2-ol and from (S)-trans-4-hexen-3-ol has been completed. The key stereodetermining step is a [2,3]-Wittig rearrangement of a propargyl ether. Elaboration of the rearrangement product was accomplished by means of a selective hydroboration-oxidation of a terminal alkyne, Horner-Emmons homologation of the derived aldehyde, followed by selective ozonolytic cleavage and Wittig olefination.