No abstract

In this article, we report the total synthesis of 6-deoxydihydrokalafungin (DDHK), a key biosynthetic intermediate of a dimeric benzoisochromanequinone antibiotic, actinorhodin (ACT), and its epimer, epi-DDHK. Tricyclic hemiacetal with 3-siloxyethyl group was subjected to Et3SiH reduction to establish the 1,3-cis stereochemistry in the benzoisochromane, and a subsequent oxidation/deprotection sequence then afforded epi-DDHK. A bicyclic acetal was subjected to AlH3 reduction to deliver the desired 1,3-trans isomer in an approximately 3:1 ratio, which was subjected to a similar sequence to that used for the 1,3-cis isomer that successfully afforded DDHK. A semisynthetic approach from (S)-DNPA, an isolable biosynthetic precursor of ACT, was also examined to afford DDHK and its epimer, which are identical to the synthetic products.

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.