Efficient chemoenzymatic synthesis of (S)- and (R)-5-(1-aminoethyl)-2-(cyclohexylmethoxy)benzamide: key intermediate for Src-SH2 inhibitor.
A facile chemoenzymatic synthesis of both the S and R forms of 5-(1-aminoethyl)-2-(cyclohexylmethoxy)benzamide a key intermediate of non-peptidic Src SH2 inhibitors is described. Both the enantiomers were synthesized in high optical purity (>99% ee) by reduction followed by lipase-mediated acylation of the precursor 6 in one-pot. Immobilized Pseudomonas cepacia lipase offered high degree of enantioselectivity with spontaneity.
Kamal
Ahmed
A
Biotransformation Laboratory, Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India. ahmedkamal@iict.ap.nic.in
Sandbhor
Mahendra
M
D000215:Acylation; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D001565:Benzoates / Q000737:chemistry; D016956:Burkholderia cepacia / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D004800:Enzymes, Immobilized / Q000187:drug effects; D008049:Lipase / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D018909:src Homology Domains; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
D001549:Benzamides; D001565:Benzoates; D004791:Enzyme Inhibitors; D004800:Enzymes, Immobilized; D019061:src-Family Kinases; D008049:Lipase