Enzyme-Catalyzed Stereoselective Synthesis of Two Novel Carbasugar Derivatives


Gumus A., TANYELİ C.

HELVETICA CHIMICA ACTA, cilt.93, ss.1882-1893, 2010 (SCI İndekslerine Giren Dergi) identifier

  • Cilt numarası: 93 Konu: 10
  • Basım Tarihi: 2010
  • Dergi Adı: HELVETICA CHIMICA ACTA
  • Sayfa Sayıları: ss.1882-1893

Özet

Enzymatic resolution of racemic 1,4,5,6-tetrachloro-2-(hydroxymethyl)-7,7-dimethoxybicyclo[2.2.1]hept-5-ene (rac-1) using various lipases in vinyl acetate as acetyl source was studied. The obtained enantiomerically enriched (+)-(1,4,5,6-tetrachloro-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-yl)methyl acetate ((+)-2; 94% ee), upon treatment with Na in liquid NH3, followed by Amberlyst-15 resin in acetone, provided (-)-5-(hydroxymethyl)bicyclo[2.2.1]hept-2-en-7-one ((-)-7), which is a valuable precursor for the synthesis of carbasugar derivatives. Subsequent Baeyer-Villiger oxidation afforded a nonseparable mixture of bicyclic lactones, which was subjected to LiAlH4 reduction and then acetylation. The resultant compounds (-)-11 and (+)-12 were submitted to a cis-hydroxylation reaction, followed by acetylation, to afford the novel carbasugar derivatives (1S,2R,3S,4S,5S)-4,5-bis(acetoxymethyl)cyclo-hexane-1,2,3-triyl triacetate ((-)-(13)) and (1R,3R,4R,6R)-4,6-bis(acetoxymethyl)cyclohexane-1,2,3-triyl triacetate ((-)(14)), respectively, with pseudo-C-2-symmetric configuration. The absolute configuration of enantiomerically enriched unreacted alcohol (-)-1 (68% ee) was determined by X-ray single-crystal analysis by anchoring optically pure (R)-1-phenylethanamine. Based on the configurational correlation between (-)-1 and (+)-2, the absolute configuration of (+)-2 was determined as (1R,2R,4S).