PROCESS FOR THE PREPARATION OF CRYPTOPHYCIN DERIVATIVES

摘要

Processes for the preparation of Cryptophycins of the formula (II), wherein G is (C1-C12) alkyl, (C2-C12) alkenyl, (C2-C12) alkynyl, or Ar; R<1> is halogen and R<2> is OH or glycinate ester; or R<1> or R<2> may be taken together to form an epoxide ring; or R<1> or R<2> may be taken together to form a bond; R<3> is (C1-C6) alkyl; R<7> and R<8> are each independently hydrogen or (C1-C6) alkyl; or R<7> and R<8>, may be taken together to form a cyclopropyl or cyclobutyl ring; R<9> is hydrogen, (C1-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, -(CH2)m-(C3-C5)cycloalkyl or benzyl; R<10>, R<14> is hydrogen or (C1-C6) alkyl; R<11> is hydrogen, (C1-C6) alkyl, phenyl or benzyl; R<50> is hydrogen or (=0); Y is CH, O, NR<12>, S, SO, SO2, wherein R<12> is hydrogen or (C1-C3) alkyl; R<6> is (C1-C6) alkyl, substituted (C1-C6)alkyl, (C3-C8)cycloalkyl, substituted (C3-C8)cycloalkyl, a heteroaromatic or substituted heteroaromatic group or a group of formula (IA), (IB) OR (IC). The processes involve an asymmetric crotylboration and, in the preferred embodiment, a subsequent asymmetric allylboration, providing for an efficient method for preparing Fragment A of the Cryptophycin molecule.