A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug.
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 racemic3with (+)-(R)-1-(1-naphthyl)ethylamine. The conversion of (+)-3into rosaprostol stereoisomer (-)-1awas accomplished in four steps in 56% overall yield. According to the same protocol, the second stereoisomer (+)-1cwas obtained from (-)-3in 55% overall yield. A slightly improved procedure of the last two steps of the transformation of (+)-3into (-)-1aallowed an increase in the overall yield to 64%. The remaining two stereoisomers, (-)-1band (+)-1d, were obtained from (-)-1aand (+)-1cin 71 and 68% yield, respectively, by a two-reaction sequence, in which a Mitsunobu inversion of configuration at C-5 was the key step.
Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland.
Wiesława
W
Perlikowska
Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland.
Remigiusz
R
Żurawiński
Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland.
Marian
M
Mikołajczyk
antiulcer drug; chiral resolution; rosaprostol; stereoselective synthesis; synthetic design