W. W. Epstein, H. Rilling
Sep 25, 1970
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Journal
The Journal of biological chemistry
Abstract
Abstract The isolation and characterization of an intermediate between farnesyl pyrophosphate and squalene is described. This intermediate, presqualene pyrophosphate, has been identified as 2-(2,6,10-trimethyl-1,6,9-undecatriene)-3-methyl-3-(4,8-dimethyl-3,7-nonadiene)-cyclopropylcarbinyl-pyrophosphate. Chemical reduction of presqualene pyrophosphate by LiAlH4 yielded an alcohol and a mixture of hydrocarbons. The mass spectrum of the alcohol had a fragmentation pattern characteristic of a primary alcohol and showed the alcohol to have the formula C30H49OH. A deuterated isomer of the alcohol was prepared from presqualene pyrophosphate which had been synthesized from farnesyl-1,1-2H-pyrophosphate. The mass spectrum of this alcohol established the origin of the carbinol carbon of the intermediate as C-1 of one farnesyl substituent and showed the loss of a hydrogen from C-1 of the other farnesyl moiety in the carbon system of presqualene pyrophosphate. The presence of a cyclopropane ring in presqualene pyrophosphate was indicated by the behavior of its derivatives on catalytic hydrogenation. The position of the cyclopropane ring was established by the mass spectra of the hydrogenated hydrocarbons derived from presqualene pyrophosphate. The nuclear magnetic resonance spectra of presqualene pyrophosphate and presqualene alcohol were consistent with the proposed structure. Consideration of the mechanism of synthesis of presqualene pyrophosphate has led us to postulate a configuration for the substituents on the cyclopropane ring. A mechanism for the conversion of the intermediate to squalene based on analogy with the reactions of similar organic compounds is in accord with the stereochemical requirements established for squalene biosynthesis.