Lipase-mediated kinetic resolution of (RS)-1-bromo-3-[4-(2-methoxy-ethyl)-phenoxy]-propan-2-ol to (R)-1-bromo-3-(4-(2-methoxyethyl) phenoxy) propan-2-yl acetate

Kaler, Abhishek; Meena, Vachan Singh; Singh, Manpreet; Pujala, Brahmam; Chakraborti, Asit K.; Banerjee, Uttam Chand

doi:10.1016/j.tetlet.2011.08.031

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…To a stirred solution of (RS)-2 (175 mg, 1 mmol) in THF (10 mL) containing AcOH (0.2 mL) was added LiCl (85 mg, 2 mmol). 17 The resultant mixture was stirred at r.…”

Section: (Rs)- (R)- and (S)-1-chloro-3-(2-cyanophenoxy)propan-2-ol mentioning

confidence: 99%

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Efficient Chemoenzymatic Synthesis of (RS)-, (R)-, and (S)-Bunitrolol

Banoth¹,

Chandarrao²,

Pujala³

et al. 2013

Synthesis

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A new chemical and the first chemoenzymatic synthesis of β-adrenergic receptor blocking agent bunitrolol is reported in racemic (RS) and enantioenriched forms (R and S). The intermediates (R)-and (S)-1-chloro-3-(2-cyanophenoxy)propan-2-ol intermediates were synthesized from the corresponding racemic alcohol through enzymatic kinetic resolution. The commercial available lipases PS-C and CCL exhibited complementary enantioselectivity during transesterification of the racemic alcohol with vinyl acetate affording the (R)-alcohol along with (S)-acetate and the (S)-alcohol along with (R)-acetate, respectively, and represent an example of enzymatic switch for reversal of enantioselectivity. The effects of various reaction parameters, such as temperature, time, substrate and enzyme concentration, and reaction medium, on the activity and enantioselectivity were optimized. The (R)-and (S)-alcohols were converted into (S)-and and (R)-bunitrolol, respectively, by treatment with tert-butylamine. The (R)-and (S)-acetates, obtained enzymatically were deacetylated to the corresponding alcohol by chemical hydrolysis and further converted into (S)-and and (R)-bunitrolol by chemical means. This is the first chemoenzymatic synthesis of both of the enantiomers of the drug. (RS)-, (R)-, and (S)-Bunitrolol were also synthesized following the 'all chemical' routes from (RS)-, (R)-, and (S)-epichlorohydrin via the corresponding (RS)-, (S)-, and (R)-2-cyanoglycidyl ether and the (RS)-, (R)-, and (S)-1-chloro-3-(2-cyanophenoxy)propan-2-ol intermediates with improved overall yields and better enantiomeric excesses compared to the reported processes.in greener chemistry. 16 In this context, the enzymatic kinetic resolution of a racemic secondary alcohol provides the desired scope 17 and encouraged us to design a new chemoenzymatic route for (R)-and (S)-bunitrolols (Scheme 2).The starting racemic epoxide (RS)-2 was prepared in 80% yield by the reaction of 3 with (RS)-4 in the presence of potassium carbonate in acetonitrile under reflux following the reported procedure. 10b The treatment of (RS)-2 with lithium chloride in tetrahydrofuran and acetic acid afforded the desired substrate (RS)-9 required for enzymatic kinetic resolution 18 (Scheme 3).

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“…To a stirred solution of (RS)-2 (175 mg, 1 mmol) in THF (10 mL) containing AcOH (0.2 mL) was added LiCl (85 mg, 2 mmol). 17 The resultant mixture was stirred at r.…”

Section: (Rs)- (R)- and (S)-1-chloro-3-(2-cyanophenoxy)propan-2-ol mentioning

confidence: 99%

“…15 Integrating biocatalysis in synthesis is an elegant approach to expand the organic toolbox and it adds and additional dimension in greener chemistry. 16 In this context, the enzymatic kinetic resolution of a racemic secondary alcohol provides the desired scope 17 and encouraged us to design a new chemoenzymatic route for (R)-and (S)-bunitrolols (Scheme 2).…”

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confidence: 99%

Efficient Chemoenzymatic Synthesis of (RS)-, (R)-, and (S)-Bunitrolol

Banoth¹,

Chandarrao²,

Pujala³

et al. 2013

Synthesis

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“…Biocatalytic approach has also been used for the synthesis of chiral intermediates of metoprolol. 23 To the best of our knowledge, herein, we report for the rst time the homology model of PFL and its application to validate the R-selectivity of PFL in the kinetic resolution of a racemic intermediate of metoprolol. In the present study, the racemic intermediate [(RS)-1-chloro-3-(4-(2-methoxyethyl)phenoxy)propan-2-ol] of metoprolol was chemically synthesized.…”

Section: Introductionmentioning

confidence: 99%