| 摘要 |
Prepn. of 7-(N-(1-(S)-carboethoxy-3-phenyl-propyl) (S)-alanyl)-1,4-dithia-7-azaspiro (4,4) nonane- 8(S)-carboxylic acid of formula (I) and its pharmaceutically acceptable salts comprises oxidising 1-carbobenzyloxy-4-hydroxy-(S)-proline of formula (II) using either (a) a sulphur trioxide-pyridine complex in DMSO in the presence of triethylamine or (b) ruthenium dioxide in the presence of sodium hypochlorite to give 1-carbobenzyloxy-4- keto-(S)-proline of formula (III), which is reacted with ethanedithiol in the presence of boron tirfluoride to give 7-benzyloxycarbonyl-1,4 -dithia-7-aza-spiro (4.4)-nonane-8(S) carboxylic acid of formula (IV) which is treated with aq. HBr to give 1,4-dithia-7-aza spiro (4,4) nonane-8 (S)- carboxylic acid hydrobromide of formula (V) which is reacted with N-(1-(S)-ethoxy-carbonyl-3-phenylpropyl)- (S)-alanine succinidyl amide of formula (VI) to give (I).
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