retrosynthesis

Retrosynthesis is a strategy in organic chemistry for planning the synthesis of a target molecule by working backward from the product to simpler starting materials. The aim is to identify a sequence of transformations that could assemble the target in the lab. At each step, bond disconnections reveal simpler fragments called synthons, corresponding to potential synthetic equivalents. The actual reagents used are synthetic equivalents of the synthons.

The approach was formalized by E. J. Corey in 1969, who described a logical framework for breaking down complex molecules into simpler, accessible materials. Core concepts include strategic disconnections, functional group interconversions, protecting-group decisions, and the idea of a synthesis plan as a tree of routes.

Practically, one starts with the target and applies disconnection rules to generate plausible precursors. This process is repeated until starting materials or known scaffolds are reached. Choices depend on yield, cost, scalability, stereochemistry, and reagent availability.

Advances in computing have expanded retrosynthesis into computer-aided synthesis planning (CASP). Rule-based systems, reaction databases, and machine learning models search for viable routes and rank them by feasibility or cost. These tools aid chemists but do not replace judgment, given gaps in reaction coverage and real-world constraints.

Applications include pharmaceutical development, natural product and material synthesis. Limitations include non-unique solutions, reliance on known reactions, and the potential for combinatorial explosion in complex targets.