This course explores the strategic construction of complex natural products, with particular emphasis on understanding how and why specific synthetic decisions are made. After a brief introduction to the principles of retrosynthetic analysis and molecular disconnections, the course will focus primarily on detailed case studies of total syntheses. In the opening lectures, students will be introduced to the core ideas of retrosynthesis, including strategic bond disconnections, functional group interconversions, and the logic of simplifying complex molecular architectures. This foundation will serve as a conceptual framework for analyzing complete synthetic routes. The main part of the course will examine selected total syntheses of structurally diverse natural products. For each case study, we will analyze the overall synthetic strategy, the rationale behind key bond constructions, and the choice of specific reactions. Particular attention will be given to reaction mechanisms, stereochemical control, three-dimensional selectivity, and the factors that govern chemo, regio, and stereoselectivity. Students will also discuss why certain transformations were necessary, how challenges were anticipated or overcome and and what alternative strategies might have been possible. By studying synthetic routes in detail, students will develop the ability to connect mechanistic understanding with strategic planning. The goal of the course is to train students to think critically about complex molecule synthesis, evaluate the logic behind published work, and gain deeper insight into how modern synthetic chemistry translates molecular design into practical execution.
Target group: This course is intended for graduate students in chemistry and advanced Master’s students with an interest in synthetic chemistry. It will be valuable for students working in any field where molecular construction and synthetic strategy play a role, including organic synthesis, medicinal chemistry, chemical biology, and related disciplines.
Prerequisites: Basic knowledge of organic chemistry, including reaction mechanisms, functional group transformations, and stereochemistry. Prior exposure to advanced organic chemistry or synthetic methods is beneficial but not required.
Evaluation: The course will be assessed on a pass/fail basis. Students will complete a take-home assignment in which they design a synthetic route toward a complex target molecule that we will provide. The exercise will require the development of a coherent retrosynthetic strategy, identification of key bond disconnections, and selection of suitable transformations supported by literature precedent.
Teaching format: The weekly teaching format will include two (x2) 75-minute lectures containing discussion with detailed analysis of selected total syntheses. Sessions will include interactive retrosynthetic exercises and guided discussion of reaction mechanisms and stereochemical outcomes. Recitations will be used to address questions arising from the teaching material.
ECTS: 3 Year: 2025
Track segment(s):
Service
Teacher(s):
Aleksander Bena
Christos Giannoudis
Teaching assistant(s):
Aleksander Bena
Christos Giannoudis
- Teacher: Aleksander Bena
- Teacher: Christos Giannoudis