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Department of Chemistry, University of Delhi, Delhi-110 007, India E-mail: dsrawat@chemistry.du.ac.in Fax: 91-11-27667501 Manuscript received 10 June 2013, accepted 13 June 2013 The synthesis of a cytotoxic natural ester sintenin (7a) and twenty eight of its analogues including. nitrogen-containing heterocyclic indole moiety (7b-7t), saturated (10a-10d) and unsaturated (10e-10h) amides were earned out by convenient route via one-pot Wittig reaction in aqueous medium with improved yield. A systematic structure activtiy relationship of sintenin ester was designed by chemically modified derivatives in order to get better cytotoxictty.