First chiral synthesis of the N-terminal amino acid congener of nikkomycin Z based on lipase-catalyzed enantioselective acetylation of a primary alcohol possessing two stereogenic centers

A stereoselective synthesis of a versatile chiral synthon possessing two stereogenic centers, (2S,3S)-3-[2-(5-benzyloxypyridyl)]-2-methyl-1,3-propane diol 12 (>99% ee), was achieved by using a chemo-enzymatic method. The conversion of (2S,3S)-12 to the homochiral intermediate (2S,3S,4S)-2-benzyloxycarbonylamino-4-[2-(5-benzyloxypyridyl)]-4-tert-butyldimethylsilyloxy-3-methylbutanoic acid 2 corresponding to the N-terminal amino acid congener of nikkomycin Z 1 is described.

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(2S,3S)-3-[2-(5-Benzyloxypyridyl)]-2-methyl-1,3-propane diolC16H19NO3[α]D26=-28.6 (c 0.92, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (2S,3S)

(2R,3R)-1-Acetoxy-3-[2-(5-benzyloxypyridyl)]-2-methyl-3-propanolC18H21NO4[α]D29=+19.6 (c 0.98, CHCl3)Ee = >99%Source of chirality: lipaseAbsolute configuration: (2R,3R)