Premium
Enzyme‐Catalyzed Stereoselective Synthesis of Two Novel Carbasugar Derivatives
Author(s) -
Gümüş Ayşegül,
Tanyeli Cihangir
Publication year - 2010
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201000213
Subject(s) - chemistry , stereoselectivity , absolute configuration , hydroxymethyl , cyclohexane , catalysis , stereochemistry , enantioselective synthesis , acetone , bicyclic molecule , hydroxylation , alcohol , racemic mixture , enantiomer , vinyl acetate , acetylation , kinetic resolution , medicinal chemistry , enzyme , organic chemistry , polymer , copolymer , biochemistry , gene
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 NH 3 , 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 LiAlH 4 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 (1 S ,2 R ,3 S ,4 S ,5 S )‐4,5‐bis(acetoxymethyl)cyclohexane‐1,2,3‐triyl triacetate ((−)‐( 13 )) and (1 R ,3 R ,4 R ,6 R )‐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 (1 R ,2 R ,4 S ).