The focus of this project is the development of novel approaches to the total synthesis of Annonaceous acetogenin and hydropyranone natural products. The proposed strategies make use of elements of synthetic design (modularity, convergency, two-directional and tandem reaction sequences) that will simplify and provide practical routes to complex molecular structures. In addition to the potential this research offers for the preparation of biologically relevant natural products and analogues, these studies will also assist the ongoing development of important chemical reactions. A particular emphasis is placed on olefin metathesis, and the proposed research includes cross, ring-closing and tandem metathesis processes that will broaden the scope of this powerful methodology and provide insights into factors governing metathesis reactions.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Kevin J. Quinn of the Department of Chemistry at the College of the Holy Cross. Professor Quinn's research efforts are directed at the chemical synthesis of complex natural products, an area of long-standing importance in the pharmaceutical and agricultural industries. This research will provide an ideal training ground for undergraduate coworkers by exposing them to a broad range of experimental and spectroscopic techniques and by requiring them to develop a solid understanding of conceptual and practical aspects of synthetic chemistry.
This award to the College of the Holy Cross has supported research aimed at the development of new strategies for the chemical synthesis of natural products, which are of long standing importance in the pharmaceutical industry. Specifically, we have targeted natural products with structures that make them amenable to synthetic approaches in which the powerful alkene metathesis reaction can be used as a key C=C bond forming step. Our studies on size-selective ring-closing metathesis, cross metathesis and tandem metathesis processes have resulted in the synthesis of two natural products (6-acetoxyhexadecanolide and murisolin) and progress toward two more (cis-sylvaticin and sorangicin A). Importantly, this work has helped us to gain a better understanding of factors leading to reactivity and selectivity in metathesis reactions that will help to inform future studies by us and others. Support of this award has provided opportunities for fifteen undergraduate students to actively participate all aspects of this research program - from the design of experiments to the presenation of their results. In addition to providing technical laboratory experience, this opportunity has helped to build knowledge and scientific sophistication as well as problem solving and communications skills that cannot be taught in a classroom setting. It has also motivated and prepared these students for careers in scientific and health professions - seven students are currently in or planning to enroll in PhD programs in chemistry and four more are currently in or planning to enroll in medical school.
