A Chemoenzymatic, Preparative Synthesis of the Isomeric Forms of p-Menth-1-en-9-ol: Application to the Synthesis of the Isomeric Forms of the Cooling Agent 1-Hydroxy-2,9-cineole

✍ Scribed by Stefano Serra; Claudio Fuganti; Francesco G. Gatti

• Book ID: 102178176
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 198 KB
• Volume: 2008
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200701010

✦ Synopsis

Abstract

A preparative‐scale synthesis of the four p‐menth‐1‐en‐9‐ol isomers 2a–5a has been achieved by means of two chemoenzymatic processes. Both synthetic pathways start from the enantiomeric forms of limonene that are converted into p‐mentha‐1,8‐dien‐9‐al isomers 12 and 15. The baker's yeast mediated reduction of the latter aldehydes afforded compounds 3a and 5a, respectively, with very high enantioselectivity. Moreover, chemical reduction of 12 and 15 gives the mixtures of enantiopure diastereoisomers 2a/3a and 4a/5a, respectively. PPL (Porcine pancreas lipase) mediated resolution of the latter mixtures followed by fractionating crystallization of derivatives 2b–5b allowed the enantio‐ and diastereoisomerically pure alcohols 2a–5a to be obtained. Compounds 2a–5a have then been used as starting materials for the preparation of four isomers of the cooling agent 1‐hydroxy‐2,9‐cineole (6–9). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)