Synthon

In retrosynthetic analysis, a synthon is a hypothetical unit within a target molecule that represents a potential starting reagent in the retroactive synthesis of that target molecule. The term was coined in 1967 by E. J. Corey. He noted in 1988 that the "word synthon has now come to be used to mean synthetic building block rather than retrosynthetic fragmentation structures".

It was noted in 1998 that the phrase did not feature very prominently in Corey's 1981 book The Logic of Chemical Synthesis, as it was not included in the index. Because synthons are charged, when placed into a synthesis an uncharged form is found commercially instead of forming and using the potentially very unstable charged synthons.

Example

In planning the synthesis of phenylacetic acid, two synthons are identified: a nucleophilic "COOH−" group, and an electrophilic "PhCH+2" group. Of course, both synthons do not exist by themselves; synthetic equivalents corresponding to the synthons are reacted to produce the desired reactant. In this case, the cyanide anion is the synthetic equivalent for the COOH− synthon, while benzyl bromide is the synthetic equivalent for the benzyl synthon.

The synthesis of phenylacetic acid determined by retrosynthetic analysis is thus:

Ph−CH2−Br + Na+[C≡N]− → Ph−CH2−C≡N + NaBr

Ph−CH2−C≡N + 2 H2O → Ph−CH2−C(=O)−OH + NH3

where Ph stands for phenyl.

C2 synthons - acetylene, acetaldehyde

-C2H4OH synthon - ethylene oxide

carbocation synthons - alkyl halides

carbanion synthons - Grignard reagents, organolithiums, substituted acetylides

Alternative use in synthetic oligonucleotides

This term is also used in the field of gene synthesis—for example "40-base synthetic oligonucleotides are built into 500- to 800-bp synthons".