Synthesis of chiral analogs of tamoxifen

• Grant number: 15/20588-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2015
• End date: October 31, 2016
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Diogo de Oliveira Silva
• Grantee: Evandro de Azevedo Rocha
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The discovery of new treatments for cancer is an ongoing challenge. Data from the IARC (WHO) and the INCA (Ministry of Health) show breast tumors as the dominant cause of mortality among women affected by cancer. Tamoxifen is one of the main antineoplastic drug used against breast cancer. Although it is well tolerated, tamoxifen causes adverse effects that are similar to the symptoms of menopause, and there is no efectiveness for about 1/3 of patients. New drugs similar to tamoxifen or its active metabolites are constantly under study to provide an alternative antitumor protocol more effective and less harmful. There are many methodologies reported in the literature to obtain this class of antineoplastic compounds, however none of them considers the use of amino acids in the synthesis approach or discusses the importance of the presence of stereogenic centers on tamoxifen or its analogues. The aim of this study is to synthesize novel analogues of tamoxifen with chiral groups from amino acids. The synthetic planning is based on the Eschweiler-Clarke methylation of enantiomerically pure amino acid and subsequent coupling with benzophenone, followed by McMurry reaction, and reduction with NaBH4 and I2. This new preparation strategy of antitumor derivatives of triphenylethylene allow developing an unprecedented number of substances with potential anticancer activity.