Retrosynthese

Retrosynthese, known in English as retrosynthesis, is a planning method in organic synthesis that analyzes a target molecule by working backward from its structure, breaking it into simpler precursors through a series of disconnections. The term and its practical framework were popularized by E. J. Corey in 1969, though earlier ideas about deconstructing molecules existed. The goal is to identify strategic bond disconnections that lead to readily available starting materials or known building blocks.

Central to retrosynthesis are the concepts of synthons and synthetic equivalents. A disconnection is chosen to yield chemical fragments (synthons) that would arise if a certain reaction were performed in reverse; the chemist then maps those synthons to actual reagents acting as synthetic equivalents. The process incorporates knowledge of functional group interconversions, stereochemistry, and protecting-group strategy.

Practically, a chemist constructs a retrosynthetic tree: repeatedly propose disconnections, evaluate the plausibility and practicality of each precursors, and select routes that minimize steps, use inexpensive starting materials, and avoid hazardous conditions. The forward sequence is then tested experimentally, with iterations as needed.

Retrosynthesis remains foundational in natural product synthesis, medicinal chemistry, and process development. In modern practice, computer-assisted retrosynthesis and AI-based methods aim to automate the generation of viable routes by applying reaction rules to a database of known transformations, offering alternative pathways and helping to compare feasibility and cost.

Limitations include reliance on the breadth and accuracy of reaction knowledge, the potential for large numbers of possible routes, and the need for experimental validation. While powerful, retrosynthesis remains a heuristic tool that complements hands-on experimentation and chemical intuition.