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The Masamune-Bergman cyclization or Masamune-Bergman reaction or Masamune-Bergman cycloaromatization is an organic reaction and more specifically a rearrangement reaction taking place when an enediyne is heated in presence of a suitable hydrogen donor (''Scheme 1''). It is the most famous and well-studied member of the general class of cycloaromatization reactions. It is named for Japanese-American chemist Satoru Masamune (b. 1928) and American chemist Robert G. Bergman (b. 1942). The reaction product is a derivative of 
In 2015 IBM scientists demonstrated that a reversible Masamune-Bergman cyclisation of diyne can be induced by a tip of an atomic force microscope (AFM). They also recorded images of individual diyne molecules during this process. When learning about this direct experimental demonstration Bergman commented, "When we first reported this reaction I had no idea that it would be biologically relevant, or that the reaction could someday be visualized at the molecular level.
Powerpoint
Whitney M. Erwin 2002 {{DEFAULTSORT:Bergman cyclization Rearrangement reactions Name reactions Carbon-carbon bond forming reactions Enediynes
benzene
Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen ato ...
.
The reaction proceeds by a thermal reaction or pyrolysis (above 200 °C) forming a short-lived and very reactive para-benzyne
Arynes and benzynes are highly reactive species derived from an aromatic ring by removal of two substituents. Arynes are examples of didehydroarenes (1,2-didehydroarenes in this case), although 1,3- and 1,4-didehydroarenes are also known. Arynes ar ...
biradical species. It will react with any hydrogen donor such as 1,4-cyclohexadiene
1,4-Cyclohexadiene is an organic compound with the formula C6H8. It is a colourless, flammable liquid that is of academic interest as a prototype of a large class of related compounds called terpenoids, an example being γ-terpinene. An isomer of ...
which converts to benzene. When quenched by tetrachloromethane the reaction product is a 1,4-dichlorobenzene and with methanol the reaction product is benzyl alcohol.
When the enyne moiety is incorporated into a 10-membered hydrocarbon ring (e.g. cyclodeca-3-ene-1,5-diyne in ''scheme 2'') the reaction, taking advantage of increased ring strain in the reactant, is possible at the much lower temperature of 37 °C.
Naturally occurring compounds such as calicheamicin
The calicheamicins are a class of enediyne antitumor antibiotics derived from the bacterium ''Micromonospora echinospora'', with calicheamicin γ1 being the most notable. It was isolated originally in the mid-1980s from the chalky soil, or "calich ...
contain the same 10-membered ring and are found to be cytotoxic
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'').
Cell physiology
Treating ...
. These compounds generate the diradical intermediate described above which can cause single and double stranded DNA cuts. There are novel drugs which attempt to make use of this property, including monoclonal antibodies such as mylotarg.
A biradical mechanism is also proposed for the formation of certain biomolecules found in marine '' sporolides'' that have a chlorobenzene unit as part of their structure. In this mechanism a halide salt provides the halogen. A model reaction with the enediyene ''cyclodeca-1,5-diyn-3-ene'', lithium bromide as halogen source and acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main componen ...
as hydrogen source in DMSO at 37 °C supports the theory:
The reaction is found to be first-order in enediyne with the formation of ''p''-benzyne A as the rate-limiting step. The halide ion then donates its two electrons in the formation of a new Br-C bond and radical electron involved is believed to shuttle over a transient C1-C4 bond forming the anion intermediate B. The anion is a powerful base, stripping protons even from DMSO to final product. The dibromide or dihydrogen product ( tetralin) never form.
In 2015 IBM scientists demonstrated that a reversible Masamune-Bergman cyclisation of diyne can be induced by a tip of an atomic force microscope (AFM). They also recorded images of individual diyne molecules during this process. When learning about this direct experimental demonstration Bergman commented, "When we first reported this reaction I had no idea that it would be biologically relevant, or that the reaction could someday be visualized at the molecular level.
References
External links
* ''Bergman Cycloaromatization'Powerpoint
Whitney M. Erwin 2002 {{DEFAULTSORT:Bergman cyclization Rearrangement reactions Name reactions Carbon-carbon bond forming reactions Enediynes