Chemoenzymatic Synthesis of alpha-Hydroxy-beta-methyl-gamma-hydroxy Esters: Role of the Keto-Enol Equilibrium To Control the Stereoselective Hydrogenation in a Key Step

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorMilagre, Cintia D. F.
dc.creatorMilagre, Humberto M. S.
dc.creatorMoran, Paulo J. S.
dc.creatorRodrigues, J. Augusto R.
dc.date2014-05-20T13:56:02Z
dc.date2016-10-25T17:05:31Z
dc.date2014-05-20T13:56:02Z
dc.date2016-10-25T17:05:31Z
dc.date2010-03-05
dc.date.accessioned2017-04-05T21:14:14Z
dc.date.available2017-04-05T21:14:14Z
dc.identifierJournal of Organic Chemistry. Washington: Amer Chemical Soc, v. 75, n. 5, p. 1410-1418, 2010.
dc.identifier0022-3263
dc.identifierhttp://hdl.handle.net/11449/20038
dc.identifierhttp://acervodigital.unesp.br/handle/11449/20038
dc.identifier10.1021/jo902227f
dc.identifierWOS:000274841400010
dc.identifierhttp://dx.doi.org/10.1021/jo902227f
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/865788
dc.descriptionalpha-Hydroxy-beta-methyl-gamma-hydroxy esters not only are found in many natural products and potent drugs but also are useful intermediates in organic synthesis due to their highly functionalized skeleton that can be further manipulated and applied in the synthesis of many compound with remarkable biological activities. This work was based on a chemoenzymatic approach to obtain these molecules with three contiguous stereogenic centers in a highly enantio- and diastereoselective way. Two distinct linear routes were proposed in which the key steps in both routes consisted of initial stereocontrolled ketoester bioreduction followed by unsaturated carbonyl bioreduction or reduction with Pd-C. Other key reactions in the synthesis include a Wasserman protocol for chain homologation and a Mannnich-type olefination with maintenance of enantiomeric excess for all intermediates during the sequence. Whereas route A gave exclusively the skeleton with 3R,4R,5S configuration (99% ee and 11.5% global yield after 7 steps), route B gave the skeleton with 3R,4R,5S and 3R,4S,5R configurations (dr 1:12, 98% ee and 20% global yield after 5 steps).
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageeng
dc.publisherAmer Chemical Soc
dc.relationJournal of Organic Chemistry
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.titleChemoenzymatic Synthesis of alpha-Hydroxy-beta-methyl-gamma-hydroxy Esters: Role of the Keto-Enol Equilibrium To Control the Stereoselective Hydrogenation in a Key Step
dc.typeOtro


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