120586-50-7Relevant articles and documents
Synthesis, resolution, and determination of the absolute configuration of the enantiomers of cis-4,5-dihydroxy-1,2-dithiane 1,1-dioxide, an HIV-1 NCp7 inhibitor
Mayasundari, Anand,Rice, William G.,Diminnie, Jonathan B.,Baker, David C.
, p. 3215 - 3219 (2003)
The anti-HIV activity of (±)-cis-4,5-dihydroxy-1,2-dithiane 1,1-dioxide [(±)-cis-1,1-dioxo-[1,2]-dithiane-4,5-diol, NSC-624151] and its attack on the zinc finger domain of the HIV-1 nucleocapsid p7 (NCp7) protein has been established [Rice, W. G.; Baker, D. C.; Schaeffer, C. A.; Graham, L.; Bu, M.; Terpening, S.; Clanton, D.; Schultz, R.; Bader, J. P.; Buckheit, R. W.; Field, L.; Singh, P. K. Turpin, J. A. Antimicrob. Agents Chemother. 1997, 41, 419]. In order to determine which enantiomer of NSC-624151 is the more active component, the compound was resolved via its bis-'Mosher ester', which was prepared via its reaction with two equiv of (-)-(R)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride. The diastereoisomeric esters were separated, and each ester was hydrolyzed to yield enantiomers with [α]D21 +151° (c 0.5, MeOH) and [α]D21 -146° (c 0.5, MeOH). Single-crystal X-ray analysis of the (-)-bis-'Mosher ester' showed that the (-)-enantiomer is the (4S, 5R)-compound. The (-)-enantiomer (NSC 693195) was ca. twice as active (EC50 8.8±0.2 μM) as its (+)-counterpart (NSC 693194) (EC50 16.2±2.4 μM) in the XTT assay against HIV-1. All three compounds were found to be approximately equally effective in promoting Zn ejection from the NCp7 zinc finger. As the more anti-HIV active enantiomer is only slightly more active than the racemic form, it appears to offer no advantages over the racemic form.