Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/01/15 05:34:15」(JST)

wiki en

In retrosynthetic analysis, a synthon is a destructural^{[clarification needed]} unit within a molecule which is related to a possible synthetic operation. The term was coined in 1968 by E.J. Corey.^[1] He noted in 1988 that the "word synthon has now come to be used to mean synthetic building block rather than retrosynthetic fragmentation structures".^[2] It was noted in 1998 ^[3] that the phrase did not feature very prominently in Corey's 1981 book, The Logic of Chemical Synthesis,^[4] as it was not included in the index.

Example

In planning the synthesis of phenylacetic acid, two synthons are identified: a nucleophilic "-COOH" group, and an electrophilic "PhCH₂⁺" group. Of course, both synthons do not exist per se; 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:

PhCH₂Br + NaCN → PhCH₂CN + NaBr

PhCH₂CN + 2 H₂O → PhCH₂COOH + NH₃

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".^[5]

Carbanionic synthons

Comparison between retrosynthetic analysis and the chemical synthesis for an ester alkylation

In 1968, E. J. Corey introduced the concept of a synthon in retrosynthetic analysis.^[6] Planning the steps of a complex molecule synthesis requires recognizing key synthons and identifying how they can be assembled into a desired product.^[7] In many retrosynthetic bond disconnections, the bond is broken heterolytically instead of homolytically, generating a carbocationtic and a carbanionic synthon. Most polar-mechanism reactions, whether they are nucleophilic displacements, 1,2-carbonyl additions, Michael reactions, or other processes, involve the fusion of a nucleophilic fragment and an electrophilic fragment.

There are a wide variety of carbanionic synthons available to the organic chemist for the construction of complex molecules. These include enolates, organometallics, acetylides, malonates, and carbanions generated in situ after addition to olefins. An example of a carbanionic synthon for an ester enolate is shown in fig. 1. A carbon-carbon bond alpha to a carbonyl can usually be disconnected to an enolate equivalent and a carbon electrophile. In this case, the enolate is generated by direct deprotonation of the substrate with lithium diisopropyl amide (LDA) base. The electrophile is methyl iodide.

Since synthons are idealized structures, it is often difficult to find equivalent chemical compounds in the real world. Many carbanion synthons, as drawn, present stability issues that render the molecule’s existence in reality impossible. For example, an acyl anions are not stable species, but the acyl anion synthon can be used to represent reagents such as lithiated dithianes, which are nucleophilic and often used in umpolung chemistry^[8]

References

^ E.J. Corey (1967). "General methods for the construction of complex molecules" (PDF). Pure and Applied Chemistry. 14: 30–37.
^ E. J. Corey (1988). "Robert Robinson Lecture. Retrosynthetic thinking—essentials and examples". Chem. Soc. Rev. 17: 111–133. doi:10.1039/CS9881700111.
^ W.A. Smit, A.F. Buchkov, R.Cople (1998). Organic Synthesis, the science behind the art. Royal Society of Chemistry. ISBN 0-85404-544-9.
^ Elias James Corey; Xue-Min Cheng (1995). The logic of chemical synthesis. Wiley-Interscience. ISBN 0-471-11594-0.
^ Sarah J. Kodumal; Kedar G. Patel; Ralph Reid; Hugo G. Menzella; Mark Welch & Daniel V. Santi (November 2, 2004). "Total synthesis of long DNA sequences: Synthesis of a contiguous 32-kb polyketide synthase gene cluster". PNAS. 101 (44): 15573–15578. Bibcode:2004PNAS..10115573K. doi:10.1073/pnas.0406911101.
^ Corey, E. J. Pure App. Chem. 1967. 14, 30–37.
^ Corey, E. J. Chem. Soc. Rev. 1988, 17, 111-133
^ Smith, A. B. III: Adams C. M. Acc Chem. Res. 2004. 37, 365-377

English Journal

Synthesis of Chiral Cyclopentenones.

Simeonov SP1, Nunes JP2, Guerra K3, Kurteva VB1, Afonso CA3.
Chemical reviews.Chem Rev.2016 Apr 21. [Epub ahead of print]
The cyclopentenone unit is a very powerful synthon for the synthesis of a variety of bioactive target molecules. This is due to the broad diversity of chemical modifications available for the enone structural motif. In particular, chiral cyclopentenones are important precursors in the asymmetric syn
PMID 27101336

Selective Synthesis and Derivatization of Germasilicon Hydrides.

Stueger H1, Christopoulos V1, Temmel A1, Haas M1, Fischer R1, Torvisco A1, Wunnicke O2, Traut S2, Martens S2.
Inorganic chemistry.Inorg Chem.2016 Apr 18;55(8):4034-8. doi: 10.1021/acs.inorgchem.6b00349. Epub 2016 Mar 31.
Mixed Si/Ge hydrides SixGeyHz are valuable precursors for the deposition of binary Si-Ge alloys. This work describes the synthesis and full characterization of the previously unknown germaisotetrasilane Ph3GeSi(SiH3)3 (2) on a multigram scale from the reaction of the lithium silanide LiSi(SiH3)3 wit
PMID 27031097

1,7-Naphthodiyne: a new platform for the synthesis of novel, sterically congested PAHs.

Pozo I1, Cobas A2, Peña D1, Guitián E1, Pérez D1.
Chemical communications (Cambridge, England).Chem Commun (Camb).2016 Apr 12;52(32):5534-7. doi: 10.1039/c6cc01214k.
The synthesis of an efficient precursor of the novel 1,7-naphthodiyne synthon is reported. Preliminary experiments demonstrate the usefulness of this platform for the synthesis of sterically congested polyarenes, such as helicenes and angularly fused acene derivatives. Furthermore, a novel intramole
PMID 27030320

Japanese Journal

EFFICIENT PREPARATION OF A VERSATILE CHIRAL SYNTHON FOR 1,2-DIAMINES VIA THE Fe(Ⅲ)-CATALYZED DIASTEREOSELECTIVE OXIDATION OF 2-IMIDAZOLONE AND ITS APPLICATION (Dedicated to Professor Isao Kuwajima on the occasion of his 77th birthday)

Matsunaga Hirofumi,Eshita Iori,Ando Shin [他]
Heterocycles : an international journal for reviews and communications in heterocyclic chemistry 90(2), 874-882, 2015-01-01
NAID 40020329988

HIGHLY EFFICIENT PREPARATION OF BOTH ENANTIOMERS OF VERSATILE CHIRAL SYNTHON FOR 1,2-DIAMINES VIA THE Fe(Ⅲ)-CATALYZED OXIDATION OF 2-IMIDAZOLONE (Dedicated to Professor Victor Snieckus on the occasion of his 77th birthday)

Matsunaga Hirofumi,Eshita Iori,Tsunoda Shoichi [他]
Heterocycles : an international journal for reviews and communications in heterocyclic chemistry 88(2), 1337-1353, 2014-01-01
NAID 40019928135