Natural product synthesis: (+/-)-rhazinilam, (+/-)-rhazinal, and PF1018.

摘要

A challenge in the field of organic synthesis is the development of synthetic methods that selectively activate C-H bonds to form carbon-carbon bonds. Organic chemists have historically ignored the C-H bonds of organic molecules because the high bond strength (e.g. 105 kcal/mol for the C-H bonds of methane, and 110 kcal/mol for benzene) was thought to be insurmountable to activation thereby making them inert to most common organic reagents. In the last decade, the ability to achieve and control reactivity of C-H bonds has undergone significant growth. This is mainly due to stoichiometric metal mediated reactions being rendered catalytic. We have developed new and more concise syntheses of natural products that take advantage of novel C-H activation strategies.;Described herein is the total synthesis of rhazinilam and rhazinal demonstrating the first catalytic direct coupling of the C3 pyrrole nucleus to an arene in synthesis. In addition to using this reaction we developed an oxidative cyclization protocol and applied it to the total synthesis of rhazinal as well.;The second part of this dissertation describes efforts aimed at a biomimetic synthesis of a complex secondary metabolite, PF1018. In particular, my research in this project has been focused on a biomimetic cascade as a means of providing a unique and step-economical route to this interesting natural product. These efforts constitute remarkable progress and illustrate the work done towards testing our key hypothesis and building important intermediates.