Efficient Synthesis of the Ketone Body Ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and Its (S,S) Enantiomer

Noah Budin, Erin Higgins, Anthony DiBernardo, Cassidy Raab, Chun Li, Scott Ulrich

Bioorg Chem. 2018 Oct;80:560-564.

PMID: 30014924

Abstract:

The ketone body ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and its (S,S) enantiomer were prepared in a short, operationally simple synthetic sequence from racemic β-butyrolactone. Enantioselective hydrolysis of β-butyrolactone with immobilized Candida antarctica lipase-B (CAL-B) results in (R)-β-butyrolactone and (S)-β-hydroxybutyric acid, which are easily converted to (R) or (S)-ethyl-3-hydroxybutyrate and reduced to (R) or (S)-1,3 butanediol. Either enantiomer of ethyl-3-hydroxybutyrate and 1,3 butanediol are then coupled, again using CAL-B, to produce the ketone body ester product. This is an efficient, scalable, atom-economic, chromatography-free, and low cost synthetic method to produce the ketone body esters.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP3068880	β-Butyrolactone		3068-88-0	Price
AP5405414	Ethyl 3-hydroxybutyrate		5405-41-4	Price