Abstract

The study of the fundamental chemical and biological activity of complex natural products is key to understanding their mechanism of action and developing therapeutics for the treatment of diseases. This research program aims to develop efficient synthesis of structurally complex, chemically intricate and biologically active natural products through the application and development of new strategies and methodologies for organic synthesis. Strategies inspired by biogenetic considerations are pursued to afford potentially broader solutions to families of compounds while providing insight into the possible biosynthetic paths responsible for their biogenesis. Targets are selected on the basis of interesting and novel molecular architecture, paucity of prior synthetic studies, biological activity, and the potential for future chemical and biological mechanistic studies. ? ? The planned syntheses are designed to develop new complexity generating sequence of reactions, in particular multiple carbon-carbon bond forming cascades and to challenge existing synthetic methods in addition to inspire the development of new and efficient methodologies for the synthesis of complex molecules. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM074825-04
Application #
7476292
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Schwab, John M
Project Start
2005-08-10
Project End
2010-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
4
Fiscal Year
2008
Total Cost
$267,776
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Antropow, Alyssa H; Garcia, Nicholas R; White, Kolby L et al. (2018) Enantioselective Synthesis of (-)-Vallesine: Late-Stage C17-Oxidation via Complex Indole Boronation. Org Lett 20:3647-3650
Kang, Taek; White, Kolby L; Mann, Tyler J et al. (2017) Enantioselective Total Synthesis of (-)-Deoxoapodine. Angew Chem Int Ed Engl 56:13857-13860
Antropow, Alyssa H; Xu, Kun; Buchsbaum, Rachel J et al. (2017) Synthesis and Evaluation of Agelastatin Derivatives as Potent Modulators for Cancer Invasion and Metastasis. J Org Chem 82:7720-7731
Xu, Kun; Tian, Xuejun; Oh, Sun Y et al. (2016) The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis. Breast Cancer Res 18:14
White, Kolby L; Mewald, Marius; Movassaghi, Mohammad (2015) Direct Observation of Intermediates Involved in the Interruption of the Bischler-Napieralski Reaction. J Org Chem 80:7403-11
Liu, Fan; Movassaghi, Mohammad (2015) Electrophilic Carbonyl Activation: Competing Condensative Cyclizations of Tryptamine Derivatives. Tetrahedron Lett 56:2995-3000
Amaike, Kazuma; Loach, Richard P; Movassaghi, Mohammad (2015) Direct C7 Functionalization of Tryptophan. Synthesis of Methyl (S)-2-((tert-Butoxycarbonyl)amino)-3-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol-3-yl)propanoate. Organic Synth 92:373-385
Han, Sunkyu; Morrison, Karen C; Hergenrother, Paul J et al. (2014) Total synthesis, stereochemical assignment, and biological activity of all known (-)-trigonoliimines. J Org Chem 79:473-86
Loach, Richard P; Fenton, Owen S; Amaike, Kazuma et al. (2014) C7-derivatization of C3-alkylindoles including tryptophans and tryptamines. J Org Chem 79:11254-63
Mewald, Marius; Medley, Jonathan William; Movassaghi, Mohammad (2014) Concise and enantioselective total synthesis of (-)-mehranine, (-)-methylenebismehranine, and related Aspidosperma alkaloids. Angew Chem Int Ed Engl 53:11634-9

Showing the most recent 10 out of 32 publications