A stereocontrolled synthesis of Cl6 Summary:
-PAF ( 11) from (S)-(-)-malic acid (I), employing regioselective hydrogenolytic cleavage of benzyEdene acetal derivatives of (S)-I,2,4butanetriol (1) with borane-tetrahydrofran complex, is described. 1-0-A1kyl-2-0-acetyl-sn-glyceryl-3-phosphorylcholine, in which the alkyl component is largely comprised of the C1s and C,s homologues has been identified as platelet activating factor (PAF) by Hanahan et al. 1 and Benveniste et al. 2 in 1979. In the same year, it also was shown to be identical with hypotensive substances designated as the antihypertensive polar renomodullary lipid (APRL) by Muirhead et al. 3 The potent and diverse biological features of PAF4-6 have stimulated many synthetic studies of them and their analogs and much research on the biological properties of these synthesized substances in recent years. Since only the natural isomers of PAF have been reported to be biologically active, 7,B their enantioselective synthesis starting from optically active natural sources such as D-mannitol' and D-tartaric acid 10 as the chiral synthons has become of interest. We now wish to report another efficient and stereocontrolled method for synthesizing PAF which uses readily available (S)-(-)-malic acid as the starting material and employs regioselective hydrogenolytic cleavage of benzylidene acetal derivatives of (S)-1,2,4_butanetriol with the borane-tetrahydrofuran complex. (S)-1,2,4-Butanetriol (z), obtained from (S)-(-)-malic acid (1) by reduction with borane-dimethylsulfide complex, 11 was converted into (S,S)-2-phenyl-, (S,S)-2-(2-methoxyphenyl)-and (S,S)-2-(4-methoxyphenyl)-4-hydroxymethyl-l,3-dioxane (2, & and 2) by reaction with benzaldehyde, 2-methoxybenzaldehyde and 4-methoxybenzaldehyde respectively in the presence of a catalytic amount of trifluoroacetic acid in CH,C1,.12 Alkylation of these compounds with n-hexadecylmethanesulfonate and potassium hydride in benzene at 40°C proceeded smoothly to give the corresponding (S,S)-P-phenyl-, (S,S)-2-(2-methoxyphenyl)and (S,S)-2-(4-methoxyphenyl)-4-hexadecyloxymethyl-l,3-dioxane (3, * and g).
First, we tried to find out the condition to convert these benzylideneacetal derivatives into the corresponding (S)-2-O-benzyl-, (S)-2-O-(3-methoxybenzyl)-or (5)-2-O-(4-3.