STUDIES ON SELECTIVE REDUCTIONS OF RAPAMYCIN

The reaction of rapamycin (1) with different reductive agents has been studied. As expected, the C-14 ketone of the ''tricarbonyl'' unit is the most electrophilic center in the molecule and could be selectively converted to either the alcohol (Zn/AcOH or DIBAL) or to the C-14 met hylene (H2S, pyridine/MeOH). Under Luche's conditions, the C-14 carbon yl was protected and reduction took place stereoselectively at both C- 24 and C-30 (NaBH4/CeCl3) or exclusively at C-30 (NaBH3CN/CeCl3). Sele ctive reaction at C-30 also took place under Evans conditions with NaB H(OAc)(3). These reactions allow the selective manipulation of the rap amycin ''effector domain''.