Regioselective synthesis of new EWG-Bearing 3-benzoyl-2-phenylbenzofurans by one-pot intramolecular acylation/thermal cyclization of phosphoranes and their CB1 antagonist activity

Michela Begala

Supervision

;Michele Mancinelli

Second

Formal Analysis

;Rafaela Mostallino

Formal Analysis

;Maria Paola Castelli

Penultimate

Formal Analysis

;Giovanna Lucia Delogu

Last

Formal Analysis

2024-01-01

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Abstract

(Benzoylmethylene)triphenylphosphoranes are useful intermediates in the synthesis of 3-benzoyl-2-phenylbenzofurans. Under Wittig conditions, they allow the simultaneous preparation of two 3-acyl regioisomers. Starting from the o-[(benzoyloxy)benzylidene]triphenylphosphonium salt bearing electron withdrawing groups (EWGs) on the ortho-benzoyloxy ring (nitro, cyano and trifluoromethyl groups), we developed an improved regioselective synthetic strategy, via tandem ylide acylation and thermal cyclization of the acyl ylide intermediate. Using our optimized method, only one 3-acyl regioisomer was obtained and the yields were highly improved (up to 92 %) comparing to the previously reported method, expanding the scope of synthesis to a wide variety of new EWG-containing 3-benzoyl-2-phenylbenzofurans. The synthesized compounds were evaluated for their activity on CB1 receptors. In particular, some of these compounds displayed activity as CB1 antagonists.