Iron(II) promoted direct synthesis of dibenzo[b,e]oxepin-11(6H)-one derivatives with biological activity. A short synthesis of doxepin

TETRAHEDRON

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Article

Scoccia, Jimena¹  Julia Castro, M.^1,2  Belen Faraoni, M.¹  Bouzat, Cecilia²  Martin, Victor S.³  Gerbino, Dario C.¹ 

[1] Univ Nacl Sur, CONICET, Dept Quim, INQUISUR, Ave Alem 1253, RA-8000 Bahia Blanca, Buenos Aires, Argentina

[2] Univ Nacl Sur, CONICET, Dept Biol Bioquim & Farm, INIBIBB, Camino La Carrindanga Km 7, RA-8000 Bahia Blanca, Buenos Aires, Argentina

[3] Univ La Laguna, Dept Quim Organ, IUBO, C Astrofis Francisco Sanchez 2, E-38206 Tenerife, Spain

关键词: Synthetic methodology;    Dibenzo[b,e]oxepin-11(6H)-ones;    Intramolecular acylation;    Doxepin;    Anthelmintic activity;   

DOI  :  10.1016/j.tet.2017.03.085

来源: Elsevier

【 摘 要 】

A novel and efficient synthesis of dibenzo[b,e]oxepin-11(6H)-ones by direct intramolecular ortho-acylation from readily available 2-(phenoxymethyl)benzoic adds was developed. The method takes advantage of a newly developed cooperative system consisting of sustainable FeCl2 and Cl2CHOCH3 as the key components, This methodology is compatible with a wide variety of functional groups in good to excellent yields and high regioselectivity. The synthetic application of new protocol was extended to the synthesis of known tricyclic drug doxepin as well as a small library of oxepin based derivatives. For the first time, the obtained dibenzo[b,e]oxepinone derivatives were evaluated for their biological activities on the free-living nematode Caenorhabditis elegans as an effective and cost-efficient model system for anthelmintic discovery. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

Free