Synthesis of Cyclosporine. I. Synthesis of enantiomerically pure (2S,3R,4R,6E)-3-hydroxy -4-methyl-2-methylamino-6-octenoic acid starting from tartaric acid

Starting from R,R-(+)-tartaric acid, the synthesis of (2S,3R,4R6E)-3-hydroxy -4-methyl-2-methylamino-6-octenoic acid in 24 steps is reported. This novel amino acid is found in the cyclic undecapeptide cyclosporin A, isolated from the fungal strain Tolypocladium inflatum GAMS . Its stereospecific synthesis allowed, for the first time, the isolation and characterization of the new amino acid previously reported as the ‘C-9-amino acid’ [1].