Discovery and development of efficient methods for the enantioseiective synthesis (preparation of a handed molecule in a single hand form) of organic molecules is critical to the successful development of efficacious new therapeutics. Such methods allow therapeutics to become accessible in a highly desirable pure form, at a low cost and without generation of toxic side products. Such factors that can significantly reduce the amount of time between the initial discovery and availability to patients from all economic segments of the society. Among such useful synthesis methods, those that are promoted by a catalyst (where small amounts of a catalysts lead to a lot of highly valuable product) and promote carbon-carbon bond formation (one of the most common bonds in nature) are particularly significant. In this proposal, we propose to design, discover and develop several new and user-friendly catalysts for the preparation of C-C bonds that will prove critical to the synthesis of a wide range of medicinally important and biologically active molecules. Our projects will have several important features: a) They focus on new catalysts that can be used on other important reactions and not just those that will be studied by us;that is, our new catalyst will have a broad impact on the research of scientists elsewhere interested in accomplishing the above goals, b) Our studies focus on the development of methods that deliver important molecules that cannot be prepared by any other protocol, or If they can, they are far less efficient. We will design and develop methods that allow chemists to take readily available and relatively inexpensive materials and convert them, with the aid of catalysts developed in this project, to highly valuable compounds that can be used to access precious medicinally active agents. In addition to designing new catalysts and methods, through applications to synthesis of biologically active molecules, we are also interested in demonstrating the utility of such methods, as well as identifying their shortcomings.

Public Health Relevance

In this program, we develop catalysts that efficiently promote reactions that can be used to prepare, in a timely and cost effective manner, a wide range of molecules that are critical to human health care and would otherwise not be accessible. Therefore, In conjunction with developing new and unique catalysts, we test the utility of such catalysts by applying them to the preparation of biologically active molecules.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM047480-22
Application #
8514004
Study Section
Special Emphasis Panel (NSS)
Program Officer
Lees, Robert G
Project Start
1992-05-01
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
22
Fiscal Year
2013
Total Cost
$336,403
Indirect Cost
$121,449
Name
Boston College
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
045896339
City
Chestnut Hill
State
MA
Country
United States
Zip Code
02467
Li, Xiben; Meng, Fanke; Torker, Sebastian et al. (2016) Catalytic Enantioselective Conjugate Additions of (pin)B-Substituted Allylcopper Compounds Generated in situ from Butadiene or Isoprene. Angew Chem Int Ed Engl 55:9997-10002
Shi, Ying; Hoveyda, Amir H (2016) Catalytic SN2'- and Enantioselective Allylic Substitution with a Diborylmethane Reagent and Application in Synthesis. Angew Chem Int Ed Engl 55:3455-8
Meng, Fanke; Li, Xiben; Torker, Sebastian et al. (2016) Catalytic enantioselective 1,6-conjugate additions of propargyl and allyl groups. Nature 537:387-393
Shi, Ying; Jung, Byunghyuck; Torker, Sebastian et al. (2015) N-Heterocyclic Carbene-Copper-Catalyzed Group-, Site-, and Enantioselective Allylic Substitution with a Readily Accessible Propargyl(pinacolato)boron Reagent: Utility in Stereoselective Synthesis and Mechanistic Attributes. J Am Chem Soc 137:8948-64
Gao, Fang; Carr, James L; Hoveyda, Amir H (2014) A broadly applicable NHC-Cu-catalyzed approach for efficient, site-, and enantioselective coupling of readily accessible (pinacolato)alkenylboron compounds to allylic phosphates and applications to natural product synthesis. J Am Chem Soc 136:2149-61
Jang, Hwanjong; Jung, Byunghyuck; Hoveyda, Amir H (2014) Catalytic enantioselective protoboration of disubstituted allenes. Access to alkenylboron compounds in high enantiomeric purity. Org Lett 16:4658-61
Meng, Fanke; Haeffner, Fredrik; Hoveyda, Amir H (2014) Diastereo- and enantioselective reactions of bis(pinacolato)diboron, 1,3-enynes, and aldehydes catalyzed by an easily accessible bisphosphine-Cu complex. J Am Chem Soc 136:11304-7
Meng, Fanke; McGrath, Kevin P; Hoveyda, Amir H (2014) Multifunctional organoboron compounds for scalable natural product synthesis. Nature 513:367-74
McGrath, Kevin P; Hoveyda, Amir H (2014) A multicomponent Ni-, Zr-, and Cu-catalyzed strategy for enantioselective synthesis of alkenyl-substituted quaternary carbons. Angew Chem Int Ed Engl 53:1910-4
Hoveyda, Amir H (2014) Evolution of catalytic stereoselective olefin metathesis: from ancillary transformation to purveyor of stereochemical identity. J Org Chem 79:4763-92

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