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oai:riuma.uma.es:10630/142802026-02-03T11:51:17Zcom_10630_2254col_10630_37959

Total synthesis of depudecin and analogues via an olefin cross-metathesis based strategy Cheng-Sánchez, Iván Sarabia-García, Francisco Ramón Antineoplásicos Total synthesis Natural products Antitumor Agents Depudecin (-)-Depudecin (1), isolated from the culture broths of the fungus Alternaria brassicicola [1], has been identified as a selective inhibitor of histone deacetylases (HDAC) with an IC50 in the low μM range. In contrast to representative HDAC inhibitors, depudecin represents a unique inhibitor of these enzymes by virtue of its molecular structure, featuring the presence of two oxirane rings separated by a trans double bond. Originally discovered as part of a biological screen directed towards the identification of antitumour agents with detransforming activity [2], depudecin was identified as a bioactive metabolite capable of reverting the transformed morphology of tumor cells. Depudecin induced cell cycle arrest and cellular differentiation [3], and also exhibited anti-angiogenesis activity [4]. Prompted by its striking biological properties and enticing structure, we decided to initiate a research program directed towards the synthesis of natural depudecin which has recently culminated with a linear total synthesis [5]. In order to develop an improved access to natural depudecin and analogues for further biological screenings, we explored a synthetic alternative as a shorter and more convergent approach. In this communication we report a new total synthesis of the natural product (-)-depudecin. A key feature of the synthesis is the utilization of an olefin cross-metathesis strategy, which provides for an efficient and improved access to natural depudecin. This strategy was applied to the preparation of the 10-epi and (+)-depudecin, which represent interesting stereoisomeric analogues for SAR studies. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. 2017-07-20T09:44:46Z 2017-07-20T09:44:46Z 2017 2017-07-20 conference output http://hdl.handle.net/10630/14280 http://orcid.org/X0000-0002-5149-3576 eng 20th European Symposium on Organic Chemistry (ESOC 17) Colonia, Alemania Julio, 2017 by-nc-nd open access application/pdf