Estrone derived 2-naphthol analogue in the diastereoselective one-pot Betti-condensation.

The utility of deoxy-isoequilenine synthesized from estrone as valuable 2-naphthol analogue is demonstrated in the three components Betti-condensation. A simple, efficient and green procedure for the synthesis of aminobenzylnaphthol analogues (so-called Betti bases) has been realized highly diastereoselectively by using (S)-phenylethylamine and 1- or 2-naphthaldehyde. The absolute configuration of the new chiral compounds obtained has been determined by means of NMR experiments and confirmed by X-ray crystallography. The chiral steroidal aminobenzylnaphthols have been evaluated as pre-catalysts for the addition of diethylzinc to aldehydes with enantioselectivities of up to 98% ee.

Anti-enteroviral activity of new MDL-860 analogues: Synthesis, in vitro/in vivo studies and QSAR analysis.

A series of 60 nitrobenzonitrile analogues of the anti-viral agent MDL-860 were synthesized (50 of which are new) and evaluated for their activity against three types of enteroviruses (coxsackievirus B1, coxsackievirus B3 and poliovirus 1). Among them, six diaryl ethers (20e, 27e, 28e, 29e, 33e and 35e) demonstrated high in vitro activity (SI > 50) towards at least one of the tested viruses and very low cytotoxicity against human cells. Compound 27e possesses the broadest spectrum of activity towards all tested viruses in the same way as MDL-860 does. The most active derivatives (27e, 29e and 35e) against coxsackievirus B1 were tested in vivo in newborn mice experimentally infected with 20 MLD50 of coxsackievirus B1. Compound 29e showed promising in vivo activity (protection index 26% and 4 days lengthening of mean survival time). QSAR analysis of the substituent effects on the in vitro cytotoxicity (CC50) and anti-viral activity of the nitrobenzonitrile derivatives was carried out and adequate QSAR models for the anti-viral activity of the compounds against poliovirus 1 and coxsackievirus B1 were constructed.