Enzyme-Catalyzed Stereoselective Synthesis of Two Novel Carbasugar Derivatives

Gumus A., TANYELİ C.

HELVETICA CHIMICA ACTA, vol.93, no.10, pp.1882-1893, 2010 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 93 Issue: 10
  • Publication Date: 2010
  • Doi Number: 10.1002/hlca.201000213
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1882-1893
  • Middle East Technical University Affiliated: Yes


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).