Trapping of Oxonium Ylides with Michael Acceptors: Highly Diastereoselective Three-Component Reactions of Diazo Compounds with Alcohols and Benzylidene Meldrum’s Acids/4-Oxo-enoates

Abstract

Trapping of oxonium ylides with a number of Michael acceptors via a 1,4-addition fashion has been investigated. Benzylidene Meldrum's acids and 4-oxo-enoates have been found to be matched components as suitable Michael acceptors for the transformation. Thus, Rh 2 (OAc) 4 -catalyzed three-component reactions of diazo compounds, alcohols, and benzylidene Meldrum's acids/4-oxo-enoates gave corresponding a-hydroxyesters in good yield with high to excellent diastereoselectivity. Synthetic utility of this efficient method was demonstrated by conversion of the addition product to a g-butyrolactone through simple procedures.

Comparative analysis of PknB inhibitors for reactivity and toxicity

“…While other PknB inhibitors reported adhere well to PAINS and Lipinski chemical properties, YH-8 revealed a characteristic highly reactive Michael acceptor, with recent organic synthesis methodology reports indicating its use as such [20][21][22][23]. Additional SAR studies by Xu et al indicate that the double bond Michael acceptor linking the ketone and ester moieties was essential for its PknB inhibition.…”