1133438-98-8Relevant articles and documents
Experimental and computation studies on Candida antarctica lipase B-catalyzed enantioselective alcoholysis of 4-bromomethyl-β-lactone leading to enantiopure 4-bromo-3-hydroxybutanoate
Lim, Jung Yun,Jeon, Nan Young,Park, A-Reum,Min, Bora,Kim, Bum Tae,Park, Seongsoon,Lee, Hyuk
, p. 1808 - 1816 (2013/07/19)
Both enantiomers of optically pure 4-bromo-3-hydroxybutanoate, which is an important chiral building block in the syntheses of various biologically active compounds including statins, were synthesized from rac-4-bromomethyl-β- lactone through kinetic resolution. Candida antarctica lipase B (CAL-B) enantioselectively catalyzes the ring opening of the β-lactone with ethanol to yield ethyl (R)-4-bromo-3-hydroxybutanoate with high enantioselectivity (E>200). The unreacted (S)-4-bromomethyl-β-lactone was converted to ethyl (S)-4-bromo-3-hydroxybutanoate (>99% ee), which can be further transformed to ethyl (R)-4-cyano-3-hydroxybutanoate, through an acid-catalyzed ring opening in ethanol. Molecular modeling revealed that the stereocenter of the fast-reacting enantiomer, (R)-bromomethyl-β-lactone, is ～2 A from the reacting carbonyl carbon. In addition, the slow-reacting enantiomer, (S)-4-bromomethyl-β-lactone, encounters steric hindrance between the bromo substituent and the side chain of the Leu278 residue, while the fast-reacting enantiomer does not have any steric clash. Copyright
