Olefin metathesis converts relatively simple olefinic substrates to complex asymmetric compounds in a clean and efficient manner, and has been shown to eliminate many steps in a synthesis of a target organic molecule. Olefin metathesis is thus of considerable interest in the synthesis of medicinally and biologically significant molecules. With more efficient and selective reactions and catalysts available, therapeutic candidates can be made available to the public more readily and in a more cost effective manner. The main objectives of this program involve the design, synthesis, characterization, and mechanistic exploration of a wide variety of new asymmetric molybdenum- and tungsten-based olefin metathesis catalysts. In addition, these novel chiral catalysts will be used to carry out unique enantioselective C-C bond forming reactions of significant interest to synthetic organic chemists. Particular emphasis will be placed on reactions that lead to the formation of products that cannot be prepared easily through any of the available catalytic or enzymatic routes. Among the reactions of interest will be asymmetric ring-closing, ring-opening, and cross metathesis reactions. In a number of cases the utility of the newly developed reactions will be demonstrated through application to the preparation of biologically significant molecules. The catalysts, methods and concepts that emerge from the proposed studies will allow chemists to access a wider range of molecules of biological interest more efficiently, reliably, and in a highly enantioselective fashion.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059426-06
Application #
6876571
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2000-03-01
Project End
2008-02-29
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
6
Fiscal Year
2005
Total Cost
$490,487
Indirect Cost
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
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Nguyen, Thach T; Koh, Ming Joo; Mann, Tyler J et al. (2017) Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis. Nature 552:347-354
van der Mei, Farid W; Miyamoto, Hiroshi; Silverio, Daniel L et al. (2016) Lewis Acid Catalyzed Borotropic Shifts in the Design of Diastereo- and Enantioselective ?-Additions of Allylboron Moieties to Aldimines. Angew Chem Int Ed Engl 55:4701-6
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