| 摘要 |
Preparation of enantiomerically pure cyclopentane beta -amino acid compounds of formula (I) comprises (a) reaction of meso-dicarboxylic acid anhydride of formula (II) with an alkenol of formula (III) in the presence of an equimolar amount of a chiral base and in an inert solvent to give an enantiomerically pure ester of formula (IV); (b) conversion of (IV) into the enantiomerically pure acid (IVa) of formula (IV; E = H); (c) conversion to the azide by (1) Curtius rearrangement by reacting (IVa) with an azide of formula (R<6>O)2P(O)N3 (V) in the presence of a base and in an inert solvent, or (2) activation of carboxyl group of (IVa) and reaction with an alkali azide or trialkylsilylazide; (d) reaction to the isocyanate of formula (VI); (e) reaction with (III) to give the diester of formula (VII); and (f) cleavage of the urethane and ester functions in an inert solvent in the presence of a Pd catalyst and/or a phosphine and a nucleophilic reagent. A, D = H, halo, OH or 1-8C alkyl (optionally mono- or di-substituted by halo, OH, Ph, benzyloxy, COOH, 1-6C alkoxy, 1-6C acyl, 1-6C alkoxycarbonyl or NR<7>R<8>); or A and D together form =CR<1>R<2>; E = chiral amine base; R<1>, R<2> = H, halo, 1-8C alkyl, 1-8C alkoxy, 1-8C hydroxyacyl, benzyl or Ph; R<4>, R<5> = H, 1-5C alkyl or Ph, (optionally mono- to tri- substituted by halo, CN, OCF3, NO2, CF3, 1-6C alkyl or 1-6C alkoxy); R<3> = as for R<4>, or 5-7 membered heteroaromatic with 3 heteroatoms from S, N and/or O; R<6> = Ph or 1-6C alkyl; R<7>, R<8> = H, Ph or 1-6C alkyl. The enantiomer-pure compounds (IV), (IVa) and (VII) are new. |
