Highly stereoselective reduction of haloketones using three new yeasts: application to the synthesis of (S)-adrenergic β-blockers related to propranolol

Lagos, Fernando Martı́nez; Carballeira, José Daniel; Bermúdez, José Luis; Álvarez, Emilio; Sinisterra, J. V.

doi:10.1016/j.tetasy.2004.01.024

Cited by 33 publications

(7 citation statements)

References 22 publications

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“…It is worth highlighting that when both enantiopure forms of epichlorohydrin (entries 3-4) were used, the regioselective ringopening occurred in parallel with a very good stereospecificity, thus improving previous procedures described 25 for the synthesis of optically active 4b and 4c, which are crucial building blocks in the synthesis of b-adrenergic blocking agents. 26 The efficiency of the proposed N-functionalization protocol was afterwards confirmed also in the case of substituted phthalimides (Table 4).…”

Section: 22mentioning

confidence: 68%

2-Methyltetrahydrofuran as a suitable green solvent for phthalimide functionalization promoted by supported KF

et al. 2010

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Section: 22mentioning

confidence: 68%

2-Methyltetrahydrofuran as a suitable green solvent for phthalimide functionalization promoted by supported KF

et al. 2010

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“…Arylglycidyl ethers have been found to be very useful organic intermediates in the synthesis of amino alcohols. [17] These amino alcohols have shown significant biological activities as adrenergic β-blockers and as muscle relaxants. [18] Bromohydrins can also very easily be converted into the corresponding amino alcohols.…”

Section: Resultsmentioning

confidence: 99%

Monobromoborane - Dimethyl Sulfide—a Highly Promising Reagent for the Regio- and Chemoselective Brominative Cleavage of Terminal Epoxides into Vicinal Bromohydrins

Roy

Brown

2007

Aust. J. Chem.

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Monobromoborane-dimethyl sulfide (BH 2 Br-SMe 2 ) is a highly regio-and chemoselective reagent useful for the brominative cleavage of the epoxy moiety into bromohydrins in the presence of alkenes, alkynes, ethers, acetals, ketals, and acetonides at 0 • C, besides being an excellent hydroborating reagent. Several reactive functional groups, such as chloride, ketones, esters, nitriles, nitros, and thioethers, have been accommodated during such transformations. Although the reduction of acetophenone was completely suppressed at −25 • C, 4-chlorobenzaldehyde still underwent 12-13% reduction of an aldehydic group.

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“…1-chloro-3-(phthalimidyl)-propan-2-on (33) Fig. (13) was proposed to become a new chiral building block that can be used to conventionally prepare the (S)-adrenergic β-blockers of a structure 1 [52]. Still, the results obtained in the reduction of this haloketone 33 were disappointing.…”

Section: A Hydroxyketonesmentioning

confidence: 99%

“…In case of reduction of substrate 32 the best ee values were reported for Yarrowia lipolytica and Pichia mexicana (achieving (S) -and (R)-halohydrin respectively) [54]. From the data presented [52,54] it can be deduced that Y. lipolytica, P. mexicana and S. bayanus are three interesting strains for the process of optimization and scaleup studies. They present a high tolerance to the substrate since the conversion rates and ee values remain high in these cases, especially for the first strain.…”

Section: A Hydroxyketonesmentioning

confidence: 99%

Biocatalytic Approaches to Optically Active β-Blockers

Żelaszczyk¹,

Kieć‐Kononowicz

2007

CMC

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Beta-blockers are a very important group of drugs widely used for the treatment of cardiovascular diseases. All aryloxyaminopropanols are chiral and show different stereoselectivity in their pharmacodynamic and pharmacokinetic properties for each enantiomer. The more potent beta-adrenoceptor blocking activity is generally associated with (S)-enantiomers. Most beta-blocking agents are sold as racemates although (R)-enantiomers not only show in some cases lack of activity but might be responsible for undesirable effects. Among reports on the direct enzymatic resolution of the most representative beta-blocker propranolol, the most interesting is N-acetylation method with commercially available lipases to yield (S)-N-acetylpropranolol. Another type of the one-step (S)-isomer biocatalytic preparation from racemic mixture of propranolol is the biodegradation with the fungus. Biocatalytic methods of obtaining homochiral beta-blockers that are focused on production of versatile precursors are widely described in literature. The strategies based on the use of glycidol and derivatives as C-3 synthones have been shown to be extremely useful for the introduction of the 2-propanol chain on the aromatic system. Halohydrins are the established intermediates in the preparation of optically active beta-blockers. Its resolution by esterhydrolases has been used as a standard alternative in preparation of the homochiral propranolol. Additionally, the enzymatic resolution of the following intermediates was reported: 1-azido-3-aryloxy-2-propanols, 4-(1-aryloxy)-3-hydroxybutyric acid esters, glycerol and cyanohydrin derivatives. However, even the highly enantioselective lipase-catalyzed process can only provide 50% of the starting racemate in an optically active form. An alternative method such as a reduction of a prochiral ketone by various strains of yeast might quantitatively provide an enantiomeric product with a yield greater than 50%. The reported substrates for microbial reductions were: 1-halo-aryloxypropan-2-ones and 1-acetoxy-aryloxypropan-2-ones.

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Highly stereoselective reduction of haloketones using three new yeasts: application to the synthesis of (S)-adrenergic β-blockers related to propranolol

Cited by 33 publications

References 22 publications

2-Methyltetrahydrofuran as a suitable green solvent for phthalimide functionalization promoted by supported KF

2-Methyltetrahydrofuran as a suitable green solvent for phthalimide functionalization promoted by supported KF

Monobromoborane - Dimethyl Sulfide—a Highly Promising Reagent for the Regio- and Chemoselective Brominative Cleavage of Terminal Epoxides into Vicinal Bromohydrins

Biocatalytic Approaches to Optically Active β-Blockers

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Highly stereoselective reduction of haloketones using three new yeasts: application to the synthesis of (S)-adrenergic β-blockers related to propranolol

Cited by 33 publications

References 22 publications

2-Methyltetrahydrofuran as a suitable green solvent for phthalimide functionalization promoted by supported KF

2-Methyltetrahydrofuran as a suitable green solvent for phthalimide functionalization promoted by supported KF

Monobromoborane - Dimethyl Sulfide—a Highly Promising Reagent for the Regio- and Chemoselective Brominative Cleavage of Terminal Epoxides into Vicinal Bromohydrins

Biocatalytic Approaches to Optically Active &#946;-Blockers

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Biocatalytic Approaches to Optically Active β-Blockers