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Steve M. Weinreb

  • Russell and Mildred Marker Professor of Natural Products Chemistry
537 Chemistry Building
Phone: (814) 863-0189

Research Interests

Synthesis of natural products; development of new synthetic methods; heterocyclic chemistry; pericyclic reactions and cycloadditions.

Total Synthesis of Heterocyclic Natural Products

Professor Weinreb's research group is currently involved in the total synthesis of a number of complex heterocyclic natural products with significant pharmacological activity. Thoughout all of these projects, heavy emphasis is being placed on developing and exploiting new synthetic methodology of potentially wide application in organic chemistry. For example, the unusual polycyclic marine natural product sarain A will be synthesized from the tricyclic intermediate in Figure 1. This compound has been prepared via the key allylsilane-N-sulfonyliminium ion cyclization shown in the figure. In addition, work is presently in progress on total synthesis of the biogenetically related anticancer marine alkaloid madangamine A.


A novel method for amide oxidation has been developed using the free radical sequence shown in Figure 2. This process provides a simple, convenient access to N-acylimines, which are widely useful synthetic intermediates. This chemistry is now being applied in an approach to total synthesis of the marine sponge anticancer alkaloid fasicularin.


A new type of pericyclic ene reaction of allenylsilane imines and related compounds has recently been discovered (Figure 3). This methodology provides a stereospecific route to diverse functionalized nitrogen-containing ring systems. The chemistry is currently being utilized in enantioselective total syntheses of the poison frog neurotoxin (-)-gephyrotoxin and the indole alkaloid (-)-ibogamine.


Several other complex marine natural products are also presently targets for total synthesis. Included in this group is the unique hepatotoxin cylindro-spermopsin produced by a fresh water blue-green alga. The key steps in this synthesis utilize methodolgy previously developed in the Weinreb group. The approach involves the intramolecular N-sulfinylurea [4+2]-cycloaddition shown in Figure 4, followed by a stereospecific ring opening-allylic sulfoxide [2,3]-sigmatropic rearrangement.

Steve M. Weinreb
  • A.B., Cornell University, 1963
  • Ph.D., University of Rochester, 1967

Representative Publications

G. Han, M. G. LaPorte, J. J. Folmer, K. M. Werner, and S. M. Weinreb, A New Enantioselective Approach to Total Synthesis of the Securinega Alkaloids. Application to (-)-Norsecurinine and Phyllanthine, Angewandte Chemie International Edition English, 39:237 (2000).

D. Stien, G. T. Anderson, C. E. Chase, Y.-H. Koh, and S. M. Weinreb, Total Synthesis of the Antitumor Marine Sponge Alkaloid Agelastatin, J. Am .Chem. Soc., 121:9574 (1999).

X. Lin, D. Stien, and S.M. Weinreb, A New Method for the Generation and Cyclization of Iminyl Radicals via the Hudson Reaction, Organic Letters, 1:637 (1999).

O. Irie, K. Samizu, J. R. Henry, and S. M. Weinreb, Further Studies on Total Synthesis of Sarain A. Efforts Toward Annulation of the Macrocyclic Rings, J. Organic Chem., 64:587 (1999).

K. M. Werner, J. M. de los Santos, and S. M. Weinreb, An Intramolecular Nitrone-Olefin Dipolar Cycloaddtion-based Approach to Total Synthesis of the Cylindricine and Lepadiformine Marine Alkaloids, J. Organic Chem., 64:4865 (1999).

S. M. Weinreb, D. T. Smith, and J. Jin, Thermal and Lewis Acid Catalyzed Intramolecular Ene Reactions of Allenylsilanes, Synthesis, 509 (1998).

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