Based on the finding that 2,3-diveratryl-3-chloropropenal (1) shows anti- HIV activity in vitro, research is planned to synthesize a series of analogs and to prepare derivatives of compound 1 in order to study the structure-activity relationships in this novel type of anti-viral compound. New compounds will be prepared in which the veratryl groups are replaced, singly or doubly, with other aromatic and heteroaromatic rings. Synthetic steps require (1) preparation of aryl benzyl ketones (ArCH2COAr') and (2) Vilsmeier-Haack formylation chlorodehydration of the ketones. Moreover, the 3-chloropropenal moiety of compound 1 is an ambident substrate toward nucleophiles, and reactions are planned to explore this reactivity. Whereas secondary amines are reported to react at position-3 in similar molecules to displace chlorine, hydroxylamine, a traditional carbonyl derivatizing agent, reacts at the aldehyde carbon to afford an oxime with compound 1. Oximes and related derivatives (nitrile oxides, isoxazoles, amines) as well as products from other nucleophilic substitutions and condensations will be characterized and screened for biological activity.
