The first stereospecific approach to both enantiomers of mellein

✍ Scribed by Christian Dimitriadis; Melvyn Gill; Michael F. Harte

• Book ID: 104361233
• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Weight: 369 KB
• Volume: 8
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/s0957-4166(97)00217-6

✦ Synopsis

R)-(-)-Mellein 1 and its (S)-(+)-antipode 2 are prepared in six steps and ca. 30% overall yield from (R)-and (S)-propylene oxide, 3 and ent-3, respectively. (~) 1997 Elsevier Science Ltd Mellein (8-hydroxy-3-methyl-3,4-dihydro-lH-2-benzopyran-l-one) is the parent of an extensive class of naturally occurring dihydroisocoumarins that collectively display a wide range of biological activity. 1 Racemic 2 mellein 1+2 has been synthesised many times I but there exists to date only one report of a synthesis of mellein in homochiral form. Thus, fifty-two years after the first report of mellein as a metabolite of Aspergillus melleus, 3 Mori and Gupta 4 reported a synthesis of (R)-(-)-mellein 1 in 7.3% yield over nine steps from ethyl (R)-3-hydroxybutanoate. It is interesting in the context of the current paper that Mori had earlier made "several unsuccessful attempts to utilise optically active propylene oxide as the chiral source". 4 We report here details of the synthesis of both enantiomers, 1 and 2, of mellein, each one in ca. 30% yield over six steps from the appropriate enantiomer of propylene oxide. 5 The method is further applicable in principle to the synthesis of many substituted mellein derivatives in either stereochemical form.