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Convergent Synthesis of Both Enantiomers of 4‐Hydroxypent‐2‐ynoic Acid Diphenylamide for a Thrombin Receptor Antagonist Sch 530348 and Himbacine Analogues
Author(s) -
Zaks Alex,
Tamarez Maria,
Li Tao
Publication year - 2009
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200900322
Subject(s) - chemistry , enantiopure drug , enantiomer , alcohol , stereochemistry , chiral resolution , resolution (logic) , enantioselective synthesis , organic chemistry , catalysis , artificial intelligence , computer science
Sch 530348 and many himbacine analogues were prepared by using 4‐hydroxypent‐2‐ynoic acid diphenylamide as the only chiral material. We developed deracemization methods to prepare both enantiomers of this propargyl alcohol. These methods involved a resolution followed by inversion. The objective for the resolution step was to obtain the desired enantiomer as an ester, and undesired enantiomer as an alcohol. With ( R )‐selective lipase, this was achieved by transesterifcation for ( R )‐alcohol, and ester hydrolysis for ( S )‐alcohol. The undesired enantiomer was inverted through the corresponding tosylate to yield the desired enantiomer as the ester. Deprotection of the ester gave enantiopure alcohol as the product. These methods not only overcame the 50% yield limit in resolution, but also eliminated the need to remove the undesired enantiomer.