Dimethylolpropionic acid → Temsirolimus

Participants

Reaction Steps

The synthesis requires two steps. The first step is a microbial lipase-catalyzed acylation of rapamycin with an activated ester of 2,2-bis(hydroxymethyl)propionic acid derivative in an organic solvent. This reaction is highly regioselective, resulting in the exclusive formation of mono-42-acylated product (i.e., protected CCI-779), in nearly quantitative yield. Subsequent deprotection furnishes CCI-779 in excellent overall yield. Compared with chemical preparation, this chemo-enzymatic route offers a much shorter procedure with higher yield. Further, this method does not require any steps to protect the rapamycin's 31-OH group.

Provenance & Evidence