| 摘要 |
Preparation of cryptophycin compounds of formula (I) or their salts, comprises: (a) deprotection of an ester-amide compounds (10) with a deprotecting agent to give an ester-amide compound (10a); and (b) optionally contacting (10a) with a cyclising agent to give (I), optionally followed by salt formation: G = 1-12C alkyl, 2-12C alkenyl, 2-12C alkynyl or Ar; Ar = aromatic or heteroaromatic group (both optionally substituted); R3 = 1-6C alkyl; R4, R5 = H; or R4+R5 = double bond; R7, R8 = H or 1-6C alkyl; or CR7R8 = cyclopropyl or cyclobutyl; R9 = H, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, (CH2)m(3-5C cycloalkyl) or benzyl; m = 1-3; R10 = H or 1-6C alkyl; R11 = H, 1-6C alkyl, phenyl or benzyl; R14 = H or 1-6C alkyl; R50 = H or oxo; Y = CH, O, NR12, S, SO or SO2; R12 = H or 1-3C alkyl; R6 = 1-6C alkyl, 3-8C cycloalkyl or heteroaromatic group (all optionally substituted), or group of formula (IA)-(IC); (IA) = CH2-ph (ring substituted by R6a-R6c), -Z-Ph (ring substituted by R15-R17) and -Z-beta -naphtholene (ring substituted by R15-R17; R6a-R6c = H, 1-6C alkyl, halo, NR18R19 or OR18; R15-R17 = H, halo, 1-6C alkyl, OR18, O-aryl, NH2, NR18R19, NO2, OPO4H2, 1-6C alkoxyphenyl, S-benzyl, CONH2, CO2H, PO3H2, SO2R23 or Z'; R18, R19 = H or 1-6C alkyl; R23 = H or 1-3C alkyl; Z = (CH2)n or 3-5C cycloalkyl; n = 0-2; Z' = optionally substituted aromatic group; q = 1-2; R81 = 1-6C alkyl, 3-8C cycloalkyl, phenyl or benzyl; and R82 = base labile protecting group. |
