ジヒドロキシル化、ジヒドロキシ化

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/18 11:11:58」(JST)

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Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol.^[1]^[2]^[3]

The Sharpless dihydroxylation.

R_L = Largest substituent; R_M = Medium-sized substituent; R_S = Smallest substituent

It is common practice to perform this reaction using a catalytic amount of osmium tetroxide, which after reaction is regenerated with either potassium ferricyanide^[4]^[5] or N-methylmorpholine N-oxide.^[6]^[7] This dramatically reduces the amount of the highly toxic and very expensive osmium tetroxide needed. These four reagents are commercially available premixed ("AD-mix"). The mixture containing (DHQ)₂-PHAL is called AD-mix-α, and the mixture containing (DHQD)₂-PHAL is called AD-mix-β.^[8]

Such chiral diols are important in organic synthesis. The introduction of chirality into nonchiral reactants through usage of a chiral catalysts is an important concept in organic synthesis. This reaction was developed principally by K. Barry Sharpless building on the already known racemic Upjohn dihydroxylation, for which he was awarded a share of the 2001 Nobel Prize in Chemistry.

Reaction mechanism

The reaction mechanism of the Sharpless dihydroxylation begins with the formation of the osmium tetroxide - ligand complex (2). A [3+2]-cycloaddition with the alkene (3) gives the cyclic intermediate 4.^[9]^[10] Basic hydrolysis liberates the diol (5) and the reduced osmate (6). Finally, the stoichiometric oxidant regenerates the osmium tetroxide - ligand complex (2).

Application

Dihydroxylation in the absence of a coordinating ligand requires the use of a stoichiometric amount of osmium.^[11]^[12]^[13] Catalytic, asymmetric dihydroxylation reduces the cost of this procedure 99.9%, opening the door for advances in biomimetic and sympathetic osmates.

Asymmetric dihydroxylation has been applied to alkenes of every substitution, and high enantioselectivities have been realized for every substitution pattern. Asymmetric dihydroxylation reactions are also highly site selective, providing products derived from reaction of the most electron-rich double bond in the substrate.^[14]

Examples

The first step in the synthesis of azasugar 6 is a dihydroxylation reaction^[15] of the prochiral diene 1. Azasugars are pharmacologically relevant. The entire reaction sequence takes place in water as a reaction medium and protective groups were not required. Notice the chemoselectivity in the nucleophilic substitution of bromine by the hydroxyl group in step 2.

For another example of this reaction see: Kuwajima Taxol total synthesis

References

^ Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroeder, G.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968. (doi:10.1021/ja00214a053)
^ Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483-2547. (Review) (doi:10.1021/cr00032a009)
^ Gonzalez, J.; Aurigemma, C.; Truesdale, L. Org. Syn., Coll. Vol. 10, p.603 (2004); Vol. 79, p.93 (2002). (Article)
^ Minato, M.; Yamamoto, K.; Tsuji, J. J. Org. Chem. 1990, 55, 766-768. (doi:10.1021/jo00289a066)
^ Oi, R.; Sharpless, K. B. Org. Syn., Coll. Vol. 9, p.251 (1998); Vol. 73, p.1 (1996). (Article)
^ VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 1973-1976.
^ McKee, B. H.; Gilheany, D. G.; Sharpless, K. B. Org. Syn., Coll. Vol. 9, p.383 (1998); Vol. 70, p.47 (1992). (Article)
^ Sharpless, K. B., et al. J. Org. Chem. 1992, 57, 2768-2771. (doi:10.1021/jo00036a003)
^ Corey, E.J.; Noe, M. C.; Grogan, M. J. Tetrahedron Lett. 1996, 37, 4899-4902.
^ DelMonte, A. J.; Haller, J.; Houk, K. N.; Sharpless, K. B.; Singleton, D. A.; Strassner, T.; Thomas, A. A. J. Am. Chem. Soc. 1997, 119, 9907-9908. (doi:10.1021/ja971650e)
^ Jacobsen, E. N.; Marko, I.; Mungall, W. S.; Schroeder, G.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 1968. (doi:10.1021/ja00214a053)
^ Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483-2547. (Review) (doi:10.1021/cr00032a009)
^ Gonzalez, J.; Aurigemma, C.; Truesdale, L. Org. Syn., Coll. Vol. 10, p.603 (2004); Vol. 79, p.93 (2002). (Article)
^ Noe, M. C.; Letavic, M. A.; Snow, S. L. Org. React. 2005, 66, 109. doi:10.1002/0471264180.or066.02
^ Efficient asymmetric synthesis of an azasugar in water Ulf M. Lindström, Rui Ding, Olle Hidestål Chemical Communications 2005, 1773.

English Journal

Metabolite identification of a new tyrosine kinase inhibitor, HM781-36B, and a pharmacokinetic study by liquid chromatography/tandem mass spectrometry.

Kim E, Kim H, Suh K, Kwon S, Lee G, Park NH, Hong J.SourceDepartment of Analysis, Hanmi Research Center, Hwaseong, 445-813, Korea; College of Pharmacy, Kyung Hee University, Seoul, 130-701, Korea.
Rapid communications in mass spectrometry : RCM.Rapid Commun Mass Spectrom.2013 Jun 15;27(11):1183-95. doi: 10.1002/rcm.6559.
RATIONALE: HM781-36B (1-[4-[4-(3,4-dichloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yloxy]-piperidin-1-yl]prop-2-en-1-one hydrochloride) is a new anticancer drug to treat advanced solid tumors in clinical trial. In order to understand the behavior of HM781-36B in vitro and in vivo we validated an
PMID 23650031

In vitro pharmacokinetic profile of a benzopyridooxathiazepine derivative using rat microsomes and hepatocytes: Identification of phases I and II metabolites.

Bourdon F, Lecoeur M, Verones V, Vaccher C, Lebegue N, Dine T, Kambia N, Goossens JF.SourceUniv Lille Nord de France, UDSL, EA GRIIOT, UFR Pharmacie, F-59000 Lille, France.
Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2013 Jun;80:69-78. doi: 10.1016/j.jpba.2013.02.022. Epub 2013 Mar 7.
In the present study, the in vitro metabolic behavior of a benzopyridooxathiazepine (BZN), a potent tubulin polymerization inhibitor, was investigated by liquid chromatography-UV detection (LC-UV). First, simple and fast LC-UV methods have been optimized and validated to evaluate the pharmacokinetic
PMID 23528331

Japanese Journal

A PRACTICAL SYNTHESIS OF A HYDROXYLATED SESQUITERPENE COUMARIN 10'R-ACETOXY-11'-HYDROXYUMBELLIPRENIN BY REGIOSELECTIVE DIHYDROXYLATION

Hattori Yasunao,Kinami Genki,Teruya Kenta [他]
Heterocycles : an international journal for reviews and communications in heterocyclic chemistry 87(2), 423-428, 2013-02-01
NAID 40019561792

Homogeneous Dihydroxylation of Olefins Catalyzed by OsO42－ Immobilized on a Dendritic Backbone with a Tertiary Nitrogen at Its Core Position

Fujita Ken-ichi,Inoue Kensuke,Tsuchimoto Teruhisa [他],Yasuda Hiroyuki
Chemical and Pharmaceutical Bulletin 60(12), 1594-1598, 2012
… OsO42－ immobilized on a poly(benzyl ether) dendrimer with a tertiary nitrogen at its core position efficiently catalyzed the homogeneous dihydroxylation of olefins with a low level of osmium leaching. …
NAID 130002459935