Synthesis and characterization of dolichols and polyprenols of designed geometry and chain length

Abstract

Dolichols of defined uniform chain length (C 20 to C 55) and geometry were prepared by total synthesis according to the following principle: ( E, E)- farnesol, activated as its 4-tolyl-sulfone, was condensed with 8-chloro-(6Z)-neryl benzyl ether, the sulfonyl group removed and the ether linkage cleaved by lithium/triethylamine. The resulting elongated prenol was converted again to its corresponding 4-tolysulfone; at this stage isomers were removed by chromatography. After several cycles of this C 10-elongation sequence the synthesis was completed in the same way but using 8-chloro-citronellyl benzyl ether as building block to introduce the saturated α-isoprene unit. Polyprenols with an even number of isoprene units are obtained by coupling activated geraniol with 8-chloro-(6 E)-neryl benzyl ether in the first step. 1H- and 13C-NMR data were recorded for qualitative and stereochemical comparison with natural dolichols. The versatility of this design makes it possible to synthesize dolichols with different geometry and double bond pattern.