Quickjump to Sections: Natural Product Total SynthesisReaction MethodologyCollaborationCompleted Natural Product Syntheses

Natural Product Total Synthesis

Our research group has had a long-standing interest in the synthesis of complex, biological active natural products (Schemes 1-2). Each target must possess a challenging structural motif(s) that is not well addressed by current synthetic strategy. In addition, we looking a broader question or interest presented by the molecule that can be uniquely addressed through synthesis. Selected examples of broader importance include developing compounds with promising biological activity against clinically relevant pathogenic bacteria and for treatment of cancer. This combination allows us to push the frontiers of organic chemistry while addressing the larger scientific issues. Currently, our synthetic efforts are focused on macrolides (mandelalides, isomandelalide A & madeirolide A), terpenes (steriodial furans & obtusanal) and alkaloids (lycopodium alkaloids).

Scheme 1. Select Examples of Macrolide Targets.

Scheme 2. Select Examples of Terpene and Alkaloid Targets.


Reaction Methodology

Ag-Catalyzed Cyclization (AgCC) Reactions. Metal-catalyzed cyclization offer the opportunity to access unique transformations. We are particularly interested in the reactivity of propargylic benzoate to undergo rearrangment and subsequent cyclization for accessing stereodefined 5- and 6-membered heterocyclic rings (Scheme 3). This chemistry has proven useful in our syntheses of amphidinolide C&F as well as mandelalide A. We continue to push the boundary for syntehtic utility in complex, polyfunctionalized systems.

Bifunctional Organocatalysis. Since the early days of enantioselective Robinson annulations facilitated by proline, organocatalysis has garnered the attention of the synthetic community. The explosion of research in the area in recent years has been fueled by the general mildness of the conditions, the relative ease of execution and the wide variety of chemical transformations that are possible. Our laboratory has been particularly focused in the areas of bifunctional organocatalysis - particularly using proline sulfonamide catalysts and primary amine-thioureas (Scheme 3). Our group has maintained a leading role in the proline sulfonamide catalysis through our discovery of Hua Cat in 2008. These catalysts have proven useful at accessing reactivity not accessible via other catalyst systems (e.g. catalytic Yamada-Otani reaction, catalytic Pfau d'Angelo reaction). We continue to innovate in our methodology and application in total synthesis.

Scheme 3. Select Examples of Reaction Methodology.


Collaboration

Our laboratory regularly engages in highly collaborative projects with other laboratories throughout the Chemistry Department, Oregon State University and other universities around the globe. These projects include biological evaluation of synthesized materials, computational analysis of reaction mechanism, computationally-aided catalyst design, development of new materials for energy applications and synthesis of suspected pollutants in the environment. The Carter laboratory embraces these collaborations; any individual interested in exploring a collaboration is encouraged to contact Rich Carter via email. In addition, the Carter laboratory has a rich history of partnerships with industry. These activities are augmented by the smart chemical manufacturing company Valliscor that was co-founded by Rich Carter and located in Corvallis, Oregon. Internship opportunities for students in the Carter laboratory are available as part of the student's education.


Completed Natural Product Syntheses by the Carter Laboratory

Mandelalide A: Veerasamy, N.; Ghosh, A.; Li, J.; Watanabe, K.; Serrill, J. D.; Ishmael, J. E.; McPhail, K. L.; Carter, R. G. J. Am. Chem. Soc. 2016, 138, 770-773. Abstract

Amphidinolide C: Mahapatra, S.; Carter, R. G. J. Am. Chem. Soc. 2013, 135, 10792-10803. Abstract

Senepodine G and Cermizine C: Veerasamy, N.; Carlson, E. C.; Collett, N. D.; Saha, M.; Carter, R. G. J. Org. Chem. 2013, 78, 4779-4800. Abstract

10-Hydroxylycopodine, Deacetylpaniculine and Paniculine: Saha, M.; Carter, R. G. Org. Lett. 2013, 15, 736-739. Abstract

Amphidinolide F: Mahapatra, S.; Carter, R. G. Angew. Chem. Int. Ed. 2012, 51, 7948-7951. Abstract

Cermizine D: Veerasamy, N.; Carlson, E. C.; Carter, R. G. Org. Lett. 2012, 14, 1596-1599. Abstract

Lyocopodine: Yang, H.; Carter, R. G.; Zakharov, L. N. J. Am. Chem. Soc. 2008, 130, 9238-9239. Abstract

Amphidinolide B1: Lu, L.; Zhang, W.; Carter, R. G. J. Am. Chem. Soc. 2008, 130, 7253-7255. Abstract

Pelleteirine: Carlson, E. C.; Rathbone, L. K.; Yang, H.; Collett, N. D.; Carter, R. G. J. Org. Chem. 2008, 73, 5155-5158. Abstract

Siamenol: Naffziger, M. R.; Ashburn, B. O.; Perkins, J. R.; Carter, R. G. J. Org. Chem. 2007, 72, 9857-9865. Abstract