Process for preparing the R- and S-isomers of 2-hydroxy-methyl-2-octadecyloxymethyl-tetrahydrofuran and their use in preparing stereoisomers of pharmacologically active compounds

A process for preparing the S-isomer of 2-hydroxymethyl-2-octadecyloxymethyl-tetrahydrofuran having the formula ##STR14## comprising the steps of:

• a) reacting either 3-chloro- or 3-bromopropanol with 2-methoxypropene in the presence of the pyridinium salt of p-toluenesulfonic acid to obtain a compound having the formula ##STR15## where Hal is chloro or bromo;
• b) alkylating diethylmalonate with a compound prepared in step a) in the presence of an alcoholic solution of sodium ethoxide and an alkali metal iodide to obtain a malonic diester having the formula ##STR16## c) in a first part, reacting the diester compound prepared in step b) with an alkali metal hydride and, in a second part, reducing the compound prepared in the first part with sodium bis(2-methoxyethoxy) aluminum hydride to obtain an allylic alcohol having the formula ##STR17## d) subjecting the allylic alcohol prepared in step c) to metal-catalyzed asymmetric Sharpless epoxidation employing a system consisting of titanium tetraisopropoxide, (+)-diethyl tartrate and t-butylhydroperoxide to obtain an epoxy alcohol having the formula ##STR18## e) alkylating the epoxy alcohol prepared in step d) with n-octadecyl bromide in the presence of an alkali metal hydride and tetrabutylammonium iodide to obtain an oxirane compound having the formula ##STR19## and f) reacting the oxirane compound prepared in step e) with acetic acid in the presence of the pyridinium salt of p-toluenesulfonic acid to obtain the desired S-isomer of 2-hydroxymethyl-2-octadecyloxymethyltetrahydrofuran.