Synthesis of Chiral 3-Pyrrolines via an Anionic Annulation Approach

Technology #ua15-004

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Researchers
Isaac Chogii
Graduate Assistant, Chemistry & Biochemistry
Jon Njardarson
Professor, Chemistry & Biochemistry
Managed By
Laura Silva

Technology Background: There are seven main types of anti-hypertensives on the market now. The invention can help create either direct acting vasodilators or direct renin inhibitors.

Invention: Invention consists of a novel method to access chiral 3-pyrroline products in one step. The treatment of a gamma leaving group with a strong base results in an anion. That anion can then be intercepted by an Ellman type imine. The end result is a robust, reliable, and versatile method to create 3-pyrroline.

Advantages:

•       One step synthetic route

•       Robust applications

•       3-Pyrroline itself is component of renin inhibitors and vasodilators; invention streamlines production for these anti-hypertensives potentially reducing costs.

Applications: The invention allows for the production of 3-pyrroline in one step, making it a valuable asset for any compound that requires 3-pyrroline synthesis. One example of a product are various pyrroline based renin inhibitors and vasodilators (Yoshino, et. al). Both types of compounds can be used to combat hypertension. Drugs that have uses the pyrroline based compounds in the production of renin inhibitors have already been shown to be relatively successful in preliminary tests (Rosenberg, et. al). Other derivatives have been shown to have inhibitory effects on serotonin reuptake (Patent EP 1100501). This opens the possibility for the invention to be used as a type of SSRI.

Patent Information: Patent Pending

References:

Hertel, Larry W., and Yao-Chang Xu. Pyrrolidine and Pyrroline Derivatives Having Effects on Serotonin Related Systems. Eli Lilly And Company, assignee. Patent EP1100501. 23 May 2001. Print. <span>https://www.google.com/patents/EP1100501A1?cl=en&dq=chiral+3-pyrroline+synthesis&hl=en&sa=X&ei=barEU9OhDOPBigKB6ICIAw&ved=0CFQQ6AEwCA Effects of pyrroline on serotonin systems.</span>

Rosenberg, S. H., K. W. Woods, H. L. Sham, H. D. Kleinert, D. L. Martin, H. Stein, J. Cohen, D. A. Egan, B. Bopp, and I. Merits. “Water-soluble Renin Inhibitors: Design of a Subnanomolar Inhibitor with a Prolonged Duration of Action.” Journal of Medicinal Chemsitry 33.7 (1990): 1962-969. PubMed. PubMed, July 1990. Web. 15 July 2014. <http://www.ncbi.nlm.nih.gov/pubmed/2194033>.

Yosino, K., K. Goto, K. Yoshiizumi, T. Morita, and G. Tsukamoto. “Organic Phosphorus Compounds. 5. (4-Benzothiazol-2-ylbenzyl)amidophosphonate as Potent Calcium Antagonistic Vasodilators.” Journal of Medicinal Cemistry 33.8 (19990): 2192-196. PubMed. PubMed, Aug. 1990. Web. 15 July 2014. <http://www.ncbi.nlm.nih.gov/pubmed/2374146>.

Principal Investigator

       Name: Jon Njardarson

       Department: CBC

       Website: http://cbc.arizona.edu/njardarson/group/homepage

Licensing Manager

Laura Silva

LauraS@tla.arizona.edu

(520) 626-1557