Synthesis of Ammonium Analogues of Carbocationic Intermediates in the Conversion of Presqualene Diphosphate to Squalene

Article abstract of DOI:10.1021/jo00260a019

Ammonium analogues 5 and 7 of the primary (2) and tertiary (3) cyclopropylcarbinyl cations, respectively, proposed as reactive intermediates in the enzyme-catalyzed rearrangement of presqualene diphosphate (1) to squalene (4), were synthesized.The general strategy involved construction of the appropriately substituted cyclopropanecarboxylic acids and introduction of the amino groups by a Curtius rearrangement.When the isocyanates from the Curtius reaction were trapped with (trimethylsilyl)ethanol, the resulting carbamates were easily cleaved with fluoride ion to give excellent yields of the corresponding cyclopropylamines.Amino acid 6, an analogue of the primary cyclopropylcarbinyl cation-pyrophosphate ion pair generated during the initial step of the rearrangement, was prepared by tethering a phosphonophosphate moiety to the amino group in 5 by a three-carbon bridge.