Total synthesis of bioactive compounds: biological tests and design of new analogs

• Grant number: 12/02230-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2012
• End date: November 30, 2014
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Luiz Carlos Dias
• Grantee: Luiz Carlos Dias
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

In this work we intend to investigate short and efficient synthetic routes that allow the total synthesis of marinisporolide A, natrangins A and B, tautomycetin, the antiasthmatic agent IMC-977 (LDP-977) and analogues of isomigrastatin and migrastatin. We intend to investigate synthetic alternatives that provide larger amounts of material for further biological studies, particularly assays of inhibition of microtubule polymerization and inhibition of tumor cell migration. The most potent molecules will be evaluated in breast cancer cells (MDA-MB231, MCF-7) for determining the potency of inhibition of cell growth (antitumor activity). We also intend to allow the synthetic routes to obtain simpler structural analogues of bioactive compounds with potential pharmacological activity. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DIAS, LUIZ C.; POLO, ELLEN C.. Nhatrangin A: Total Syntheses of the Proposed Structure and Six of Its Diastereoisomers. Journal of Organic Chemistry, v. 82, n. 8, p. 4072-4112, APR 21 2017. (11/06722-2, 12/02230-0, 13/07600-3)

ZHOU, YONGJUN; PREDIGER, PATRICIA; DIAS, LUIZ CARLOS; MURPHY, ANNABEL C.; LEADLAY, PETER F.. Macrodiolide Formation by the Thioesterase of a Modular Polyketide Synthase. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, v. 54, n. 17, p. 5232-5235, APR 20 2015. (12/02230-0, 12/04616-3)

ZHOU, YONGJUN; MURPHY, ANNABEL C.; SAMBORSKYY, MARKIYAN; PREDIGER, PATRICIA; DIAS, LUIZ CARLOS; LEADLAY, PETER F.. Iterative Mechanism of Macrodiolide Formation in the Anticancer Compound Conglobatin. CHEMISTRY & BIOLOGY, v. 22, n. 6, p. 745-754, JUN 18 2015. (12/02230-0, 12/04616-3)

DIAS, LUIZ C.; DE LUCCA, EMILIO C.. Total Synthesis of (-)-Marinisporolide C. Journal of Organic Chemistry, v. 82, n. 6, p. 3019-3045, MAR 17 2017. (11/06721-6, 12/02230-0, 13/07600-3)

FERREIRA, MARCO A. B.; DIAS, LUIZ C.; LEONARCZYK, IVES A.; POLO, ELLEN C.; DE LUCCA, JR., EMILIO C.. Exploring the Aldol Reaction in the Synthesis of Bioactive Compounds. CURRENT ORGANIC SYNTHESIS, v. 12, n. 5, p. 547-564, 2015. (11/06722-2, 11/06721-6, 13/02311-3, 12/02230-0)

DIAS, LUIZ C.; DE LUCCA, JR., EMILIO C.. Total Synthesis of the Oxopolyene Macrolide (-)-Marinisporolide C. ORGANIC LETTERS, v. 17, n. 24, p. 6278-6281, DEC 18 2015. (11/06721-6, 12/02230-0, 13/07600-3)

DIAS, L. C.; KUROISHI, P. K.; DE LUCCA, JR., E. C.. The total synthesis of (-)-cryptocaryol A. ORGANIC & BIOMOLECULAR CHEMISTRY, v. 13, n. 12, p. 3575-3584, 2015. (12/02230-0, 13/07600-3)

DIAS, LUIZ C.; VIEIRA, ADRIANO S.; BARREIRO, ELIEZER J.. The total synthesis of calcium atorvastatin. ORGANIC & BIOMOLECULAR CHEMISTRY, v. 14, n. 7, p. 2291-2296, 2016. (12/02230-0)

FERREIRA, RAFAELA S.; DESSOY, MARCO A.; PAULI, IVANI; SOUZA, MARIANA L.; KROGH, RENATA; SALES, ANA I. L.; OLIVA, GLAUCIUS; DIAS, LUIZ C.; ANDRICOPULO, ADRIANO D.. Synthesis, Biological Evaluation, and Structure-Activity Relationships of Potent Noncovalent and Nonpeptidic Cruzain Inhibitors as Anti-Trypanosoma cruzi Agents. Journal of Medicinal Chemistry, v. 57, n. 6, p. 2380-2392, MAR 27 2014. (12/02230-0, 10/16778-2, 13/07600-3)