RESUMEN

Rubrolides are a family of naturally occurring 5-benzylidenebutenolides, which generally contain brominated phenol groups, and nearly half of them also present a chlorine attached to the butenolide core. Seven natural rubrolides were previously synthesized. When these compounds were tested against the model plant Raphanus sativus, six were found to exert a slight inhibition on plant growth. Aiming to exploit their scaffold as a model for the synthesis of new compounds targeting photosynthesis, nine new rubrolide analogues were prepared. The synthesis was accomplished in 2-4 steps with a 10-39% overall yield from 3,4-dichlorofuran-2(5H)-one. All compounds were evaluated for their ability to inhibit the whole Hill reaction or excluding photosystem I (PSI). Several natural rubrolides and their analogues displayed good inhibitory potential (IC50 = 2-8 µM). Molecular docking studies on the photosystem II-light harvesting complex II (PSII-LHCII supercomplex) binding site were also performed. Overall, data support the use of rubrolides as a model for the development of new active principles targeting the photosynthetic electron transport chain to be used as herbicides.

Asunto(s)

Fotosíntesis , Transporte de Electrón/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Estructura Molecular , Simulación del Acoplamiento Molecular , Complejo de Proteína del Fotosistema II/antagonistas & inhibidores , Complejo de Proteína del Fotosistema II/efectos de los fármacos , Complejo de Proteína del Fotosistema II/metabolismo , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , 4-Butirolactona/síntesis química , 4-Butirolactona/química , Herbicidas/farmacología , Herbicidas/síntesis química , Herbicidas/química

RESUMEN

A stereoselective vinylogous aldol reaction of N-monosubstituted tetronamides with aldehydes is described. The procedure is simple and scalable, works well with both aromatic and aliphatic aldehydes, and affords mainly the corresponding syn-aldol adducts. In many cases, the latter are obtained essentially free of their anti-isomers (dr > 99 : 1) in high yields (70-90%). Experimental and computational studies suggest that the observed diastereoselectivity arises through anti-syn isomer interconversion, enabled by an iterative retro-aldol/aldol reaction.