Franklin A. Davis
Laura H. Carnell Professor of Chemistry
B.S. ('62), University of Wisconsin
Medicinal / Organic
Asymmetric Synthesis using Sulfur–Nitrogen Reagents
With the realization that biological activity often critically depends on molecular shape and absolute stereochemistry, the synthesis of enantiomerically pure compounds and the elucidation of the underlying principles of molecular recognition have emerged as increasingly important objectives. The focus of our research programs at Temple is the development of new reagents and methodologies for the asymmetric synthesis of biologically and pharmacologically active amine derivatives (amino acids, amino phosphonates, and alkaloids).
Asymmetric Synthesis of Bioactive Amines. Our studies at Temple have demonstrated that sulfinimines (N-sulfinyl imines) offer a general solution to the problem of addition of organometallic reagents to imines because the N -sulfinyl group activates the C=N bond for addition, is highly stereodirecting and easily removed in the sulfinamide without epimerization of the amine product. The most direct and reliable method for the asymmetric synthesis of diverse amines is the addition of an organometallic reagent to an enantiopure sulfinimine. In this regard sulfinimines have been utilized in the asymmetric syntheses of amines; a- and b-amino acids; a- and b-amino phosphonates; nitrogen heterocycles including aziridine 2-carboxylated and 2-phosphonates; isoquinolines; 2 H-azirine carboxylates and phosphonates; pyrrolidines and piperidines.
Currently efforts are aimed at the design and synthesis of a series of sulfinimine-derived polyfunctionalized chiral building blocks for the asymmetric synthesis of bioactive nitrogen heterocycles. We require these building blocks to be easily prepared in both enantiomerically pure forms and provide efficient access to classes of amine heterocycles with a minimum of chemical manipulation.
Edupuganti, R.; Davis, F. A. “Synthesis and Applications of Masked Oxo-Sulfinamides in Asymmetric Synthesis,” Organic & Biomolecular Chemistry (2012) 10, 5021-5031.
Davis F. A., Xu, H.; “Formal Synthesis of (-)-Clavepictine A and (+)-Clavepictine B,” Heterocycles, (2012) 84, 1227-1233.
Davis, F. A.; Gaddiraju, N. V.; Theddu, N.; Hummel, J. R.; Kondaveeti, S. K.; Zdilla M. J. “Enantioselective Synthesis of Cocaine C-1 Analogs using Sulfinimines (N-Sulfinyl Imines).” Journal of Organic Chemistry (2012) 77, 2345-2359.
Reith, E. A. M.; Solav, A.; Hashim, A.; Sheikh, I. S.; Theddu, N.; Gaddiraju, N. V.; Mehrotra, S.; Schmitt, K. C.; Murray, T. F.; Sershen, H.; Unterwald, E. M.; Davis, F. A., “Novel C-1 Substituted Cocaine Analogues Unlike Cocaine or Benztropine,” Journal of Pharmacology and Experimental Therapeutics (2012) 343, 413-425
Davis, F. A.; Xu, P., “Asymmetric Synthesis of anti-a-Substituted b-Amino Ketones from Sulfinimines,” Journal of Organic Chemistry (2011) 76, 3329-3337.
Davis, FA; Zhang, J; Wu, Y; "Total syntheses of (+)-monomorine I and (-)-indolizidine 195B from sulfinimine-derived 2-oxo pyrrolidine and 2-phosphonates." Tetrahedron Letters (2011) 52, 17, 2054-2057.
Davis, FA; Theddu, N; Edupuganti, R; "Asymmetric Total Synthesis of(S)-(+)-Cocaine and the First Synthesis of Cocaine C-1 Analogs from N-Sulfinyl beta-Amino Ester Ketals." Organic Letters (2010) 12, 18, 4118-4121.
Davis, FA; Ramachandar, T; Zhang, Y; "Photodesulfinylation of optically active N-sulfinyl amines." Tetrahedron Letters (2010) 51, 31, 4020-2-44.
Davis, FA; Theddu, N; "Asymmetric Synthesis of Cyclic cis-beta-Amino Acid derivatives Using Sulfinimines and Prochiral Weinrab Amide Enolates." Journal of Organic Chemistry (2010) 75, 11, 3814-3820
Davis, FA; Edupuganti, R; " Asymmetric Synthesis of Substituted Hmotrophines from N-Sulfinyl beta-Amino Keton Ketals." Organic Letters (2010) 12, 4, 848-851
Davis, FA; Ramachandar, T; zhang, YF; "Photodesulfinylation of optically active N-sulfinyl amines." Tetrahedron Letters (2010) 51, 31, 4042-4-44
Davis, FA; Song, MS; Qui, H; " Total synthesis of (5R, 6R, 8R, 9S)-(-)-5,9Z-indolizidine 221T using sulfinimine derived N-sulfinyl beta-amino ketones." Organic & Biomolecular Chemistry (2009) 7, 24, 5067-5073
Davis, FA; Zhang, YF; "Asymmetric synthesis of (2S,3R)-(-)-epi-CP-99,994 using sulfinimine-derived anti-2,3-diamino esters." Tetrahedron Letters. (2009) 50, 37, 5205-5207
Davis, FA; Zhang, YF; "Improved Synthesis of (-)-Agelastatin A." Synthetic Communications. (2009). 39, 11, 1914-1919
Davis, FA; Theddu, N; Gaspari, PM; "Mannich Cyclization Reaction and Acyclic N-Sulfinyl beta-Amino Keton Ketals." Organic Letters (2009) 11, 7, 1647-1650
Davis, FA; Qui, H; Song, M; "Vinylaluminum to Sulfinimines (N-Sulfinyl Imines). Asymmetric Synthesis of anti-alpha-Alkyl beta-Amino Esters." Journal of Organic Chemistry (2009) 74, 7, 2798-2803
Davis, FA; Gaspari, PM; Nolt, BM; "Asymmetric Synthesis of Acyclic 1,3-Amino Alchohols by Reduction of N-Sulfinyl beta-Amino Ketones. Formal Synthesis of (-)-Pinidinol and (+)-Epipinidinol." Journal of Organic Chemistry. (2009) 73, 24, 9619-9626
Davis, F. A. Theddu, N.; Gaspari, P. A. “Asymmetric Synthesis of Substituted Tropinones using the Intramolecular Mannich Cyclization Reactions and Acyclic N-Sulfinyl -Amino Ketone Ketals.” Organic Letters (2009) 11, 164236.
For reviews on the chemistry of sulfinimines see: