title: Epi-, epoxy-, and C2-modified bengamides: synthesis and biological evaluation.
abstract: With the objective of investigating the influence of structural modifications of the polyketide chain of the bengamides upon their antitumoral activities, we targeted the preparation of bengamide E analogues with modification of the stereochemistry at C-2 and at C-3, the substituent at the C-2 position, and the presence of oxirane rings. For the synthesis of these analogues, a new synthetic method for asymmetric epoxidation, developed in our laboratories, was employed utilizing the chiral sulfonium salts 22 and 23. In order to access 2-epi-bengamide E from these epoxy amides, a synthetic methodology, developed by Miyashita, allowed an oxirane-ring-opening reaction with a double inversion of the configuration. Alternatively, an aldol reaction provided access to the same analogue in a shorter and more efficient manner. Finally, biological evaluation of all of these bengamide E analogues demonstrated that the polyketide chain is essential for the antitumor activity of these natural products, not being amenable to structural or configurational modifications.
authors: Department of Organic Chemistry, Faculty of Sciences, University of Málaga, Campus de Teatinos s/n 29071-Málaga, Spain. frsarabia@uma.es
authors: Francisco
authors: F
authors: Sarabia
authors: Francisca
authors: F
authors: Martín-Gálvez
authors: Cristina
authors: C
authors: García-Ruiz
authors: Antonio
authors: A
authors: Sánchez-Ruiz
authors: Carlos
authors: C
authors: Vivar-García
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D018922:HL-60 Cells; D019073:HT29 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010080:Oxazoles; C529256:bengazole E