Efficient synthesis and resolution of novel 2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one by lipase Pseudomonas cepacia

Lipase Pseudomonas cepacia catalyzed acylation of (±)-2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one using vinyl acetate as the acyl donor in acetone gave (−)-(R)-2-acetoxy-2-(methyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one and (+)-(S)-2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one with high enantiomeric excess. Enantiomerically pure 2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one are useful intermediates for the preparation of Ramelteon, an FDA approved drug for the treatment of insomnia.

Graphical abstractSynthesis and enzymatic resolution of novel 2-(hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)-one using vinyl acetate as the acyl donor in acetone is reported first time.Figure optionsDownload full-size imageDownload as PowerPoint slide

2-(Hydroxymethyl)-7,8-dihydro-1H-indeno[5,4-b] furan-6(2H)oneC12H13O3[α]D28=+18.5 (c 0.28, CHCl3)ee >30%Source of chirality: Enzymatic resolutionAbsolute configuration: (S)

(6-Oxo-2,6,7,8-tetrahydro-1H-indeno[5,4-b] furan-2-yl)methyl acetateC14H15O4[α]D28=-6.4 (c 0.25, CHCl3)ee >99%Source of chirality: Enzymatic resolutionAbsolute configuration: (R)