Preparation of Optically Active 2,2-Disubstituted 5-Hydroxychromenes by the Enzymatic Resolution of Racemic Esters

Abstract

Enzymatic kinetic resolution of racemic esters of 2,2-disubstituted 5-hydroxychromenes was examined. Transesterification of acetate using Amano Lipase PS in the presence of t-BuOH was most effective to give the corresponding optically active acetate in 18% yield and 95% ee. The absolute configuration of the acetate was determined as R based on the conversion to teretifolione B with natural absolute configuration. Pyranonaphthoquinone natural products are widely distributed in plants and microorganisms, and they have diverse biological activities. 1 Angular benzochromenes are a small class of natural products isolated from Conospermum and Pentas plants. 2 We have reported asymmetric total synthesis of teretifolione B (1) and the corresponding methyl derivative 2, monomeric benzochromenes isolated from Conospermum plants. 3 The key steps of this total synthesis are enzymatic resolution of racemic 2,2-disubstituted 5-hydroxychromene 3 and Diels-Alder reaction of optically active benzyne 4 and oxygen-substituted furans 5 (Scheme 1). In this paper, details of our trials for enzymatic resolution of racemic chromene 3 were reported.