| 摘要 |
Disclosed are proline-rapamycin 42-ester with 2,2-bis(hydroxymethyl)propioni c acid (proline-CCI-779) as well as a method for the regiospecific preparation of a rapamycin 42-ester or proline-rapamycin 42-ester with 2,2- bis(hydroxymethyl)propionic acid (CCI-779 and proline-CCI-779) comprising th e steps of: (a) reacting rapamycin or proline-rapamycin with an activated este r derivative of 2,2-bis(hydroxymethyl)propionic acid having the structure (A) wherein R1 and R2 are hydrogen, or taken together to form a ketal with the structure (B) wherein R3 and R4 are each, independently, hydrogen, C1-6 alky l, either linear or branched, or taken together form C5-7 cycloalkyl or taken together form cyclic boronate with the structure (C), wherein R5 is selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl and phenyl; in a suitable organic solvent in the presence of an effective amount of microbial lipase; and (b) deprotecting the intermediate resulting from step (a) to provide CCI-779 or proline-CCI-779.
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