Neurosteroid analogues. Part 5. Enantiomers of neuroactive steroids and benz[e]indenes: Total synthesis, electrophysiological effects on GABA_A receptor function and anesthetic actions in tadpoles

The synthesis of (3β,5β,8α,9β,10α,13α14β,17α)-3- hydroxypregnan-20-one 2, (3β,5β,8α,9β,10α,13α,14β,17α)-3- hydroxyandrostane-17-carbonitrile 4,†[3R-(3α,3aα,5aβ,7α,9bβ)]-1-[dodecahydro-7- (2-hydroxyethyl)-3a-methyl-1H-benz[e]inden-3-yl]ethanone 6 and [3R-(3α,3aα,5aβ,7α,9aα,9bβ)]-dodecahydro-7-(2- hydroxyethyl)-3a-methyl-1H-benz[e]indene-3-carbonitrile 8 is reported. ‡ Steroids 2 and 4 have been used previously to investigate the enantioselectivity of steroid action on GABA_A receptor function and to correlate steroid action at this receptor with the anesthetic actions of the compounds. The enantioselective actions of benz[e]indenes 6 and 8 have been evaluated for the same reasons in this study. Similar correlations between the enantioselective effects of both classes of compounds on GABAA receptor function and anesthetic potency in tadpoles have been observed.