Descriptif

Methods and strategies for natural product and drug synthesis

Total synthesis is the science of constructing valuable molecules, usually natural products and medicinal drugs, from simple starting materials or simple fragments. It is supported by retrosynthetic analysis, a problem-solving method that aims at theoretically transforming the complex structure of a target molecule into simple and commercially available starting materials. Target compounds can be prepared for applied research purpose, especially in biology and medicine, in order to solve societal problems. While allowing the preparation useful complex molecules, total synthesis also participates to the progress of organic chemistry, thanks to the development of new reactions (synthetic methodologies).

The purpose of this course is to learn students how to deal with chemical complexity in organic synthesis. Retrosynthetic principles will be exposed in order to understand how to find the best synthetic strategy depending on the structure of target compounds. Examples from the literature will be used to illustrate these strategies, while the forward synthesis will give an occasion to present useful and modern synthetic methodologies used nowadays.

As natural products are complex synthetic targets made by living organisms (plants, fungi, bacteria, animals), their biosynthetic and enzymatic origins will also be presented. This knowledge is important in the total synthesis point of view since, by inspiring the organic chemist, it can give rise to biomimetic or bio-inspired synthetic strategies.

Motivated students can complete this course with the Drug Sciences course CHI/BIO 567, which offers an additional opportunity to learn about the research and development of small molecules for medicinal purposes, including medicinal chemistry aspects.

Content of the course

• Retrosynthetic analysis, definition of a synthon
• The concept of ideal synthesis
• Carbon-carbon bond formation and functional group inter-conversions
• Problems of chemo-, regio-, diastereo-, and enantioselectivity
• Impact of new reactions on the strategies and tactics of organic synthesis (cascade reactions, metal-catalyzed reactions: metathesis, palladium-catalyzed cross-couplings...)
• Some famous examples of total syntheses.
• The main classes of natural products: polyacetates and polyketides (incl. fatty acids and phenols), metabolites of shikimic acid, polyisoprenoids (terpenes and steroids), metabolites of amino-acids (alkaloids)
• Biosynthesis of natural products, incl. some basic enzymatic reactions

Requirement: We strongly advise that students follow the advanced organic chemistry and organometallic chemistry courses during the first period.