Substrate Specificity of Farnesylpyrophosphate Synthetase. Application to Asymmetric Synthesis

Article abstract of DOI:10.1021/ja00530a050

Nine analogues of isopentenyl pyrophosphate (1) have been studied as substrates for pig liver farnesylpyrophosphate synthetase. (E)-3-Methylpent-3-enyl pyrophosphate (12) and its Z isomer 13 react enzymatically with geranyl pyrophosphate (3) to give (S)-(14) and (R)-4-methylfarnesyl pyrophosphate (15), respectively. 12 and 13 also react with dimethylallyl pyrophosphate (2) to give the corresponding enantiomers of 4-methylgeranyl pyrophosphate (17 or 19) and 4,8-dimethylfarnesyl pyrophosphate (18 or 20). 3,4-Dimethylpent-3-enyl (21), (E)-3-ethylpent-3-enyl (22), (Z)-3-ethylpent-3-enyl (23), and 2-(cyclohexen-1-yl)ethyl pyrophosphate (25) condense with 3, but they cannot react with 2. 2-(Cyclopenten-1-yl)ethyl pyrophosphate (24) is as highly reactive as 12 or 13, reacting with both 2 and 3 to give optically active products. 2-Methylprop-2-enyl (46) and 3-methylpent-4-enyl pyrophosphate (47) are inactive.