Current Targets of Interest....

Chemistry of Nitrenium Ions

Although the existence of nitrenium ions has been long been appreciated and their role as agents of carcinogenesis studied extensively, the potential of these N-electrophiles as tools for target-directed synthesis, has yet to be realized. That from a synthetic standpoint, nitrenium ions have often been viewed as the poor cousins of cations, carbenes and nitrenes, their isoelectronic congeners within the electron-deficient branch of the reactive intermediate family, is keenly apparent from the comparatively small amount of published work concerning synthetic applications of these cations. We are focused on the development of synthetic nitrenium ion chemistry and specifically on the reaction of these divalent intermediates with alkenes, a concerted process that generates aziridinium ions.

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Chemistry of Alkylidenecarbenes

The Wardrop has a long-standing interest in the generation and reaction of alkylidenecarbenes, transient, electron deficient species, which undergo a number of synthetically valuable reactions, including [1,2]-rearrangement, ylide formation, alkene cyclopropanation and [1,5]-C-H bond insertion. Over the last decade, we have studied the latter transformation as a means to access O- and N-heterocycles and natural products that encompass these ring systems. In addition to employing alkylidenecarbenes in the preparation of natural products, we are also interested in the discovery of new methods for their generation under mild conditions. In this regard, we have recently developed a mild, base-free method for the generation of alkylidenecarbenes employing the dehydrative fragmentation of 5-hydroxyalkyl-1H-tetrazoles.

Synthesis of Natural Products

In conjunction with our interests in the chemistry of alkylidenecarbenes and nitrenium ions, we are also actively involved in the total synthesis of natural products. Current targets in this regard, include the azabicyclo[3.3.1]nonane alkaloids mandangamine and suomilide, which are being accessed through our nitrenium ion methodology. Other synthetic targets include alpha-glucosidase inhibitors such as members of the schulzeine family and more traditional azasugars including australine.