Stereoselective Synthesis of γ‐(Acyloxy)carboxylic Acids and γ‐Lactones Featuring the Switch of Stereopreference of Candida antarctica Lipase B in Sodium γ‐Hydroxycarboxylate Homologues

• Published in: European Journal of Organic Chemistry
• Main Authors: Parve, Jaan, Kudryashova, Marina, Shalima, Tatsiana, Villo, Ly, Ferschel, Moonika, Niidu, Allan, Liblikas, Ilme, Reile, Indrek, Aav, Riina, Gathergood, Nicholas, Vares, Lauri, Pehk, Tõnis, Parve, Omar
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2023
• Subjects: F162 Polymer Chemistry; F100 Chemistry; F163 Bio-organic Chemistry; Antarc*; Antarctica
• Online Access: https://eprints.lincoln.ac.uk/id/eprint/53472/; https://eprints.lincoln.ac.uk/id/eprint/53472/1/ImprovedMscriptEurJOC09112022.docx; https://doi.org/10.1002/ejoc.202201329

Scalable protocols of straightforward synthesis of enantiomeric gamma-(acyloxy)carboxylic acids and gamma-lactones are presented. The key step is lipase-catalyzed stereoselective acylation of gamma-hydroxycarboxylic acid sodium salt in organic solvent followed by acidification of the product, extraction and acidic relactonization of the unreacted enantiomer. The mixture of gamma-(acyloxy)carboxylic acid and gamma-lactone is separated either by extraction with solution of sodium bicarbonate or by distillation. A switch of enantioinduction of Candida antarctica lipase B along homologous nucleophiles from R configuration of gamma-hydroxyhexanoic acid salt to S configuration of the C7 and longer-chain homologues has been disclosed. Both enantiomers of gamma-(acyloxy)pentanoic acids; gamma-(acetyloxy)octanoic and -nonanoic acids with S configuration; [(1S,5R)-5-(chloroacetyloxy)cyclopent-2-en-1-yl]acetic acid and enantiomeric gamma-lactones derived from them were prepared with e. r. > 98.5/1.5. The rates of acylation of C5 to C9 homologous salts differ by three orders of magnitude but remain applicable for preparative synthesis by variation of the enzyme loading and reaction time.