A regio- and stereo-selective synthesis of 2-hydroxy-3-methylochromycinonein three steps from 2-bromo-5-acetoxy-1,4-naphthoquinone and 1-acetoxy-3,3-dimethyl-5-vinylcyclohexa-1,5-diene

2-Hydroxy-3-methylochromycinone 4 has been synthesised using a three stage strategy. The Diels-Alder reaction between 2-bromo-5-acetoxy-1,4-naphthoqui none and 1-acetoxy-3,3-dimethyl-5-vinylcyclohexa-1,5-diene gives a single r acemic diastereoisomer of 1-acetoxy-12a-bromo-3,3-dimethyl-7,12-dioxo-3,4,6 ,6a,7,12,12a,12b-octahydrobenzo[a]anthracen-8-yl acetate 5 in 63% yield, wh ich may be epoxidised to give the bis-epoxide 8-acetoxy-12a-bromo-3,3-dimet hyl-7,8-dioxo-3,4,4a,5,6,6a,7,12,12a,12b-decahydro-1aH-benzo[6,7]oxireno[2' ,3':10,10a]phenanthro[3,4-b]oxiren-12-yl acetate 6 in 82% yield. The bis-ep oxide 6 may be converted directly into 2-hydroxy-3-methylochromycinone 4 in 45% yield, or via one of twointermediates [e.g. 2,5-dihydroxy-3,3-dimethyl -1,7,12-trioxo-1,2,3,4,5,6,7,12-octahydrobenzo[a]anthracen-8-yl acetate 8] in 80-85% yield. The intermediate 8 shows moderate anticancer activity at m uM concentrations against lung, breast and central nervous system cancers, while the target compound 4 is only active at 10(-4) M.