A novel chemo-multienzymatic synthesis of bioactive cyclophellitol and epi-cyclophellitol in both enantiopure forms

A new route to synthesize cyclophellitol and epi-cyclophellitol from racemic starting materials in enantiopure forms has been developed. The synthesis involves a multi-enzymatic biotransformation pathway of the novel cyano-cyclitol (1R,4S,5R,6R)/(1S,4R,5S,6S)-4,5,6-trihydroxycyclohex-2-enecarbonitrile by a cooperative use of lipase, nitrile hydratase, and amidase.

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(1R,4S,5R,6R)-4,5,6-Trihydroxycyclohex-2-enecarbonitrileC7H9NO3Ee = 98%[α]D25 = +135.6 (c 0.26, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (1R,4S,5R,6R)

(1S,4R,5R,6S)-4-Cyano-5,6-dihydroxycyclohex-2-enyl acetateC9H11O4Ee = 98%[α]D25 = +102 (c 0.3, H2O)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,4R,5R,6S)

(1S,4S,5R,6R)-Methyl 4,5,6-trihydroxycyclohex-2-enecarboxylateC8H12O5Ee = 98%[α]D25 = +110.3 (c 0.3, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,4S,5R,6R)

(1S,4S,5R,6R)-Methyl 4,5,6-tris(benzyloxy)cyclohex-2-enecarboxylateC29H30O5Ee = 98%[α]D25 = +98.6 (c 1.4, MeOH)Source of chirality: enzymatic resolutionAbsolute configuration: (1S,4S,5R,6R)