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Simple reagents for direct, halonium-induced cyclizations

总结

Lead Inventors: Scott Snyder, Ph.D.; Daniel Scott Treitler; Alexandria Paige BrucksProblem or Unmet Need:Although Nature has developed enzymes to incorporate halogen atoms into bioactive structures in highly effective ways, chemists have not developed tools that can broadly emulate their efficiency; as a result, accessing such molecules requires laborious, lengthy, and non-direct routes. If tools could be developed to allow the direct incorporation of halogen atoms into these structures, especially through processes that also form other critical bonds concurrently, then many interesting bioactive molecules can be made quickly, on scale, and can be probed more fully in terms of their biochemical potential. This technology describes a class of solid, readily handled reagents which are the first that can enable the direct synthesis of chlorine, bromine, and iodine-containing polycycles, including steroid-like structures, large-ring haloethers of marine origin, and analogs thereof that have not yet been obtained from natural sources. These reagents combine a Lewis acid, a Lewis base, and molecular halogen, with the lead compounds of the class known as bromodiethylsufonium bromopentachloroantimonate (BDSB) and chlorodiethylsulfonium hexachloroantimonate (CDSC). In total, the technology comprises the reagents and processes used to achieve these structures, as well as the compounds themselves.

技术优势

The new class of reagents reacts rapidly and with high chemoselectivity at low temperatures; the compounds are more easily handled than many halogen sources. The technology does not require toxic metals or added acids. In addition to enabling the synthesis of hitherto unsynthesized natural products, the technology can also be used to cyclize various substrates with higher yields than had previously been achievable with conventional methods; in some cases, other reagents do not work at all.

技术应用

The technology can be used to synthesize bioactive compounds on scale such as peyssonol A, a natural product found in certain marine algae that inhibits the reverse transcriptase enzyme in human immunodeficiency virus (HIV), along with several stereochemical isomers in an effort to improve its efficacy. Nearly every 8-membered haloether of the Laurencia class of bioactive marine natural products has been prepared in a simple, and high-yielding process. The reagents also allow for positionally unique halogenation of electron-rich aromatic rings versus alternatives as well as complex halocyclizations unachievable with other reagents.

详细技术说明

This technology describes a class of solid, readily handled reagents which are the first that can enable the direct synthesis of chlorine, bromine, and iodine-containing polycycles, including steroid-like structures, large-ring haloethers of marine o...

*Abstract

None

*Inquiry

Beth Kauderer Columbia Technology Ventures Tel: (212) 854-8444 Email: TechTransfer@columbia.edu

*IR

M10-119

*Principal Investigation

*Publications

A General Strategy for the Stereocontrolled Preparation of Diverse 8- and 9-Membered Laurencia-Type Bromoethers, Journal of the American Chemical Society, Article ASAP.Regioselective Reactions for Programmable Resveratrol Oligomer Synthesis, Nature, vol. 474, Jun. 2011, pp. 461-466.Simple Reagents for Direct Halonium-Induced Polyene Cyclization, Journal of the American Chemical Society, Vol. 132, No. 40, Sep. 2010, pp. 14303-14314.Et2SBr*SbCl5Br: An Effective Reagent for Direct, Bromonium-Induced Polyene Cyclizations, Angewandte Chemie International Edition, vol. 48, 2009, pp. 7899-7903.

国家/地区

美国