Practical asymmetric synthesis of ()-(−)-phenylephrine hydrochloride catalyzed by (2,4)-MCCPM-rhodium complex

Takeda, Hideo; Tachinami, Takeshi; Aburatani, Masakazu; Takahashi, Hisashi; Morimoto, Toshiaki; Achiwa, Kazuo

doi:10.1016/s0040-4039(00)95204-3

Cited by 38 publications

(10 citation statements)

References 6 publications

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“…The reduction of the ketone 115a with Rh-MCCPM (Rh-116) gave the corresponding alcohol in 83% but an upgrade could be realised by recrystallisation. 175 The protecting groups contribute to more than half of the formula weight of 115a. Studies on the free phenol 115b, an intermediate in the classical resolution method to 114, showed pyrrolidinone-based ligands gave Rh-catalysts that provided the best stereoselectivity and reactivity.…”

Section: Substrate Screeningmentioning

confidence: 99%

Asymmetric homogeneous hydrogenations at scale

Ager¹,

2012

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Asymmetric hydrogenations are increasingly being used to introduce stereogenic centres into products used in the life sciences industries. There are a number of potential pitfalls when moving from a laboratory reaction to a manufacturing process, not least of which is safety. Time-to-market pressure leads to short development times, which in the past could be a large barrier for the implementation of catalytic steps; now there are new ways to minimise this problem. The potential problems associated with impurities and other methods that can shut down the hydrogenation reactions are highlighted in this critical review (353 references).

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Section: Substrate Screeningmentioning

confidence: 99%

Asymmetric homogeneous hydrogenations at scale

Ager¹,

2012

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“…Thus, an asymmetric hydrogenation method is required for producing optically pure ( R )-PE 16 . A few schemes for the asymmetric synthesis of ( R )-PE have been developed 17 – 20 . However, such chemical processes demand the use of high pressure and temperature, as well as environmentally damaging organic solvents 21 .…”

Section: Introductionmentioning

confidence: 99%

Structure-guided design of Serratia marcescens short-chain dehydrogenase/reductase for stereoselective synthesis of (R)-phenylephrine

Liu

Kuan

Tsou

et al. 2018

Sci Rep

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Bioconversion is useful to produce optically pure enantiomers in the pharmaceutical industry, thereby avoiding problems with side reactions during organic synthesis processes. A short-chain dehydrogenase/reductase from Serratia marcescens BCRC 10948 (SmSDR) can stereoselectively convert 1-(3-hydroxyphenyl)-2-(methylamino) ethanone (HPMAE) into (R)-phenylephrine [(R)-PE], which is marketed medically as a nasal decongestant agent. The whole-cell conversion process for the synthesis of (R)-PE using SmSDR was reported to have an unexpectedly low conversion rate. We reported the crystal structure of the SmSDR and designed profitable variants to improve the enzymatic activity by structure-guided approach. Several important residues in the structure were observed to form hydrophobic clusters that stabilize the mobile loops surrounding the pocket. Of these, Phe98 and Phe202 face toward each other and connect the upper curvature from the two arms (i.e., the α7 helix and loopβ4–α4). The mutant structure of the double substitutions (F98YF202Y) exhibited a hydrogen bond between the curvatures that stabilizes the flexible arms. Site-directed mutagenesis characterization revealed that the mutations (F98Y, F98YF202Y, and F98YF202L) of the flexible loops that stabilize the region exhibited a higher transformation activity toward HPMAE. Together, our results suggest a robust structure-guided approach that can be used to generate a valuable engineered variant for pharmaceutical applications.

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“…The preparation of chiral alcohols was achieved by combining lipase‐catalyzed resolution with the Mitsunobu reaction . In addition, the enzymatic conversions , asymmetric dihydroxylation , asymmetric Henry reaction , and other methods were also been used to obtain nonracemic compounds. However, these methods suffered from some drawbacks, especially the use of expensive reagents.…”

Section: Introductionmentioning

confidence: 99%

A Mild and Highly Efficient Synthesis of Chiral N‐Dichloroacetyl‐4‐ethyl‐1,3‐oxazolidines

Zhao

et al. 2012

Journal of Heterocyclic Chem

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Chiral 2‐amino‐butanols (4 and 5) were obtained via the isolation of diastereomeric salt. Then, chiral compounds (6–9) were synthesized by a sequential procedure involving condensation of chiral 2‐amino‐butanol with ketone and dichloroacetyl chloride. All the compounds were characterized by IR, 1H NMR, 13C NMR, and element analysis. The absolute configurations of (S)‐8 was determined by X‐ray crystallography.

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Practical asymmetric synthesis of ()-(−)-phenylephrine hydrochloride catalyzed by (2,4)-MCCPM-rhodium complex

Cited by 38 publications

References 6 publications

Asymmetric homogeneous hydrogenations at scale

Asymmetric homogeneous hydrogenations at scale

Structure-guided design of Serratia marcescens short-chain dehydrogenase/reductase for stereoselective synthesis of (R)-phenylephrine

A Mild and Highly Efficient Synthesis of Chiral N‐Dichloroacetyl‐4‐ethyl‐1,3‐oxazolidines

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