Practical, asymmetric synthesis of the cyclohexyl C28-C34 fragment of the immunosuppressant FK-506 via (S)-(-)-3-cyclohexenecarboxylic acid

Article abstract of DOI:10.1016/S0040-4020(01)89015-3

The asymmetric synthesis of the cyclohexyl fragment of FK-506 is reported. This new synthesis (five steps, 30% overall yield) starts, for the first time, from (S)-(-)-3-cyclohexenecarboxylic acid (S-2) instead of the commonly used R form (acid R-2) and utilizes an epimerization reaction. The overall yield is improved to 35% by recycling recovered starting product (hydroxy ester 7c) from the epimerization step.