Preparation of goniothalamin under flow reaction conditions

• Grant number: 12/05909-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 01, 2012
• End date: July 31, 2013
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Ronaldo Aloise Pilli
• Grantee: Júlio Cezar Pastre
• Supervisor: Steven V. Ley
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Cambridge, England
• Associated to the scholarship: 10/16990-1 - Synthesis and evaluation of cytotoxic activity of gama-dihydropyrones: goniothalamin and abyssinone II analogues, BP.PD

Abstract

Flow chemistry is the process of performing chemical reactions in a tube or pipe. Reactive components are pumped together at a mixing junction and flowed down a temperature and pressure controlled tube. The major advantages of flow chemistry are faster reactions, cleaner products, safer reactions, quick reaction optimization, easy scale-up, and the integration of typically separate processes (such as synthesis, work-up and analysis). This flow technology has been applied quite successfully in multi-step synthesis of biologically active compounds. In an ongoing program to identify new candidates for cancer treatment, goniothalamin was recognized as a good lead compound with significant cytotoxic and antiproliferative activities against a variety of tumor cell lines. Due to our continuous effort to evaluate new goniothalamin analogues and the high potential of the flow chemistry to the synthesis of natural products and biologically active compounds, in this project we intend to explore this technology for large-scale preparation of goniothalamin and more potent derivatives. The process developed could accelerate the discovery of new anticancer agents, since the biological assays, typically performed in vivo, requires a large amount of material. (AU)

Scientific publications

(5)

(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)

PASTRE, JULIO C.; BROWNE, DUNCAN L.; LEY, STEVEN V.. Flow chemistry syntheses of natural products. CHEMICAL SOCIETY REVIEWS, v. 42, n. 23, p. 8849-8869, 2013. (12/05909-4)

PASTRE, JULIO C.; MURRAY, PHILIP R. D.; BROWNE, DUNCAN L.; BRANCAGLION, GUILHERME A.; GALAVERNA, RENAN S.; PILLI, RONALDO A.; LEY, V, STEVEN. Integrated Batch and Continuous Flow Process for the Synthesis of Goniothalamin. ACS OMEGA, v. 5, n. 29, p. 18472-18483, JUL 28 2020. (13/07607-8, 12/05909-4, 14/26378-2)

NEWBY, JAMES A.; BLAYLOCK, D. WAYNE; WITT, PAUL M.; PASTRE, JULIO C.; ZACHAROVA, MARIJA K.; LEY, STEVEN V.; BROWNE, DUNCAN L.. Design and Application of a Low-Temperature Continuous Flow Chemistry Platform. ORGANIC PROCESS RESEARCH & DEVELOPMENT, v. 18, n. 10, p. 1211-1220, OCT 2014. (12/05909-4)

PASTRE, JULIO C.; BROWNE, DUNCAN L.; O'BRIEN, MATTHEW; LEY, STEVEN V.. Scaling Up of Continuous Flow Processes with Gases Using a Tube-in-Tube Reactor: Inline Titrations and Fanetizole Synthesis with Ammonia. ORGANIC PROCESS RESEARCH & DEVELOPMENT, v. 17, n. 9, p. 1183-1191, SEP 2013. (12/05909-4)

MURRAY, PHILIP R. D.; BROWNE, DUNCAN L.; PASTRE, JULIO C.; BUTTERS, CHRIS; GUTHRIE, DUNCAN; LEY, STEVEN V.. Continuous Flow-Processing of Organometallic Reagents Using an Advanced Peristaltic Pumping System and the Telescoped Flow Synthesis of (E/Z)-Tamoxifen. ORGANIC PROCESS RESEARCH & DEVELOPMENT, v. 17, n. 9, p. 1192-1208, SEP 2013. (12/05909-4)