Pyranonaphthoquinone antibiotics. Part 1. Syntheses of 9-demethoxyeleutherins and 9-deoxynanaomycin A methyl ester

Abstract

The syntheses of 9-demethoxyeleutherins and 9-deoxynanaomycin A methyl ester starting from indan-1-one derivatives are described. Lemieux–Johnson oxidation of the indene (15) derived from 4,7-dimethoxy-2-methyl-indan-1-one (14) afforded the diketone (16). The diol (17) obtained by lithium aluminium hydride reduction of (16) was treated with hydrochloric acid to give a ca. 1 : 2 mixture of cis-5,8-dimethoxy-1,3-dimethylisochroman (18) and the trans-isomer (19). Treatment of (16) with hydrogen bromide in acetic acid followed by catalytic reduction gave exclusively the cis-isochroman (18). Oxidative demthylation of the isochromans (18) and (19) afforded the quinones (22) and (23), benzannelation of which in two steps yielded 9-demethoxyeleutherin (24) and 9-demethoxyisoeleutherin (25) respectively. The same oxidation of the indene (32) derived from 4,7-dimethoxyindan-1-one (28) afforded the keto-aldehyde (33), which was treated with methoxycarbonylmethylene-triphenylphosphorane to give the conjugated ester (34). Reductive cyclisation of (34) with sodium borohydride afforded a ca. 1 : 3.5 mixture of cis-5,8-dimethoxy-3-methoxycarbonylmethyl-1-methylisochroman (35) and the trans-isomer (36). Oxidative demethylation of (36) followed by benzannelation produced 9-deoxynanomycin A methyl ester (39).