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A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug.

ABSTRACT: Four enantiomerically pure stereoisomers of rosaprostol (1), an antiulcer drug, were efficiently synthesized from the enantiomers of 2-(dimethoxyphosphoryl)-3-hexylcyclopentanone (3) as chiral substrates. The latter were obtained by resolution of racemic 3 with (+)-(R)-1-(1-naphthyl)ethylamine. The conversion of (+)-3 into rosaprostol stereoisomer (-)-1a was accomplished in four steps in 56% overall yield. According to the same protocol, the second stereoisomer (+)-1c was obtained from (-)-3 in 55% overall yield. A slightly improved procedure of the last two steps of the transformation of (+)-3 into (-)-1a allowed an increase in the overall yield to 64%. The remaining two stereoisomers, (-)-1b and (+)-1d, were obtained from (-)-1a and (+)-1c in 71 and 68% yield, respectively, by a two-reaction sequence, in which a Mitsunobu inversion of configuration at C-5 was the key step.

SUBMITTER: Perlikowska W

PROVIDER: S-EPMC5082602 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug.

Perlikowska Wiesława W Żurawiński Remigiusz R Mikołajczyk Marian M

Beilstein journal of organic chemistry 20161021

Four enantiomerically pure stereoisomers of rosaprostol (1), an antiulcer drug, were efficiently synthesized from the enantiomers of 2-(dimethoxyphosphoryl)-3-hexylcyclopentanone (3) as chiral substrates. The latter were obtained by resolution of racemic 3 with (+)-(R)-1-(1-naphthyl)ethylamine. The conversion of (+)-3 into rosaprostol stereoisomer (-)-1a was accomplished in four steps in 56% overall yield. According to the same protocol, the second stere ...[more]

PMID: 27829932

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