An Enantioconvergent Synthesis of (R)-4-Aryloxy-1-butyne-3-ols for Prostanoid Side Chains

• Published in: Advanced synthesis & catalysis Vol. 344; no. 1; pp. 50 - 56
• Main Authors: Fox, Martin E., Jackson, Mark, Lennon, Ian C., McCague, Raymond, Parratt, Julian S.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01.01.2002; WILEY‐VCH Verlag GmbH; Wiley
• Subjects: Chemistry; Chemistry, Applied; Chemistry, Organic; enzymatic resolution; nucleophilic substitution; Physical Sciences; propargylic compounds; prostanoids; Science & Technology; propargylic compounds; PROSTAGLANDIN; prostanoids; nucleophilic substitution; enzymatic resolution
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/1615-4169(200201)344:1<50::AID-ADSC50>3.0.CO;2-5

The single enantiomer title alcohols, useful as ω‐side chain precursors for pharmaceutically important prostaglandin analogues were synthesised from the corresponding racemic alcohols by a convenient 4‐step sequence. After enzymatic acylation of the alcohol with a vinyl carboxylate, the residual (S)‐alcohol in the mixture was converted to the mesylate. Subsequent displacement with the corresponding carboxylate anion, followed by enzymatic deacylation gave the desired (R)‐alcohol. In this way, all of the starting alcohol was utilised without the need for separation of the starting material and product after the bioresolution.