Advanced Synthesis – From Nature to the Lab

 

This module builds on knowledge of core organic chemistry by exploring advanced synthetic pathways. The module is useful preparation for those planning to spend their final year carrying out a synthetic placement in industry (e.g. in the pharmaceutical/agrochemical industry). First, the module will outline how biological systems achieve the synthesis of complex natural products through biosynthetic pathways. Next, advanced retrosynthesis will be covered, in particular Diels-Alder and umpolung reactions. Aspects of stereoselective synthesis using organo-main group synthetic approaches will then feature. Finally, a range of approaches for the introduction of nitrogen into complex molecules will be discussed since nitrogen-containing functional groups are widespread in pharmaceutical and agrochemical compounds.

Learning objectives

  • to devise biosynthetic routes to polyketides, terpenes and alkaloids
  • to devise complex synthetic routes to target molecules using a range of new types of disconnections (e.g. Diels-Alder, umpolung, organo-main group reactions).
  • to understand the ways in which nitrogen can be introduced into molecules and apply these to unseen problems

Topics

Introduction to Advanced Organic Synthesis (1 workshop)

This introductory workshop will cover some of the key synthesis and retrosynthesis parts of previous core modules. It will also provide a forward look into the strategy and planning of synthesis of complex molecules.

Biosynthesis of Polyketides, Terpenes and Alkaloids (4 lectures and 1 workshop)

This course will provide an introduction to biosynthetic pathways and reactions. Specific examples of biosynthesis will focus on those types of targets covered in the rest of this module and will include: polyketides; terpenes and alkaloids.

Advanced Retrosynthesis (4 lectures and 1 workshop)

The course will explore guidelines for developing modern synthetic strategies, including formation of cyclic compounds using Diels-Alder reactions (asymmetric, intramolecular and polymer-supported reactions) and approaches using umpolung (reverse polarity) reactions. The strategies will be illustrated with the synthesis of biologically important target molecules.

Stereocontrolled Synthesis using Organo-Main Group Chemistry (4 lectures and 1 workshop)

The course will examine methods for the stereocontrolled synthesis of key functionality found in natural products using reagents that contain phosphorus, sulfur, silicon and boron. Examples based on natural product targets will include stereocontrolled formation of alkenes, vicinal (1,2) stereocentres and stereotriads (1,2,3-stereocentres).

Synthesis of Nitrogen-containing Pharmaceuticals and Natural Products (4 lectures and 1 workshop)

This course will cover the synthetic strategies used to introduce nitrogen into molecules, including: hetero Diels-Alder reactions; amide coupling strategies; cross coupling; reductive amination; Mannich reactions, nucleophilic substitution and the synthesis of pyridines, pyrroles and indoles.

Prerequisites

Chemistry Core Modules 1-7

Assessment

A written paper (70%) plus continuous assessment (30%) – 2 hour assessed workshop on Biosynthesis of Polyketides, Terpenes and Alkaloids