Development of an Acid-Washable Tag for the Separation of Enantiomers from Bioresolutions

Brossat, Maude; Moody, Thomas S.; Nanteuil, Florian de; Taylor, Stephen J.; Vaughan, Fatima

doi:10.1021/op900028d

Cited by 22 publications

(12 citation statements)

References 13 publications

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“…[D 3 ]Vinyl esters of N‐Boc‐protected glycine‐1‐ 13 C ( 2 a ) and alanine‐1‐ 13 C ( 2 b ) were prepared by using the Pd‐catalyzed transesterification reaction with . [D 6 ]vinyl acetate from the corresponding N‐Boc protected amino acids 1 a , b (see Scheme ).…”

Section: Methodsmentioning

confidence: 99%

Hyperpolarization of Amino Acids in Water Utilizing Parahydrogen on a Rhodium Nanocatalyst

Kaltschnee

Jagtap

McCormick

et al. 2019

Chemistry A European J

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NMR offers many possibilitiesi nc hemical analysis, structurali nvestigations, and medical diagnostics. Although it is broadly used, one of NMR spectroscopies main drawbacks is low sensitivity.H yperpolarization techniques enhanceN MR signals by more than four orders of magnitude allowing the design of new contrast agents. Parahydrogen induced polarization that utilizes the parahydrogen's singlet state to create enhanced signals is of particular interests ince it allows to producem olecular imagingagentswithin seconds. Herein,wepresent astrategy for signal enhancement of the carbonyl 13 Ci na mino acids by using parahydrogen,a sd emonstratedf or glycine and alanine. Importantly,t he hyperpolarizations tep is carried out in water and chemically unmodifiedc anonical amino acids are obtained. Our approach thus offers ah igh degree of biocompatibility,w hich is crucial for furthera pplication. The rapid sample hyperpolarization (withins econds) may enable the continuous productiono fb iologically useful probes, such as metabolic contrast agents or probes for structuralbiology.[e] Prof. Dr.M.U tz SchoolofC hemistry,University of Southampton SouthamptonS O171BJ (UK)Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.

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Section: Methodsmentioning

confidence: 99%

Hyperpolarization of Amino Acids in Water Utilizing Parahydrogen on a Rhodium Nanocatalyst

Kaltschnee

Jagtap

McCormick

et al. 2019

Chemistry A European J

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“…Hydrolase enzymes have been receiving increasing attention in the context of organic synthesis in the last decade. As biocatalysts, they provide substrate specificity with high regio- and enantio-selectivity and they enable the resolution of organic substrates with great efficiency and selectivity [ 13 , 14 , 15 ]. Lipases and proteases are the most utilised forms of hydrolytic enzymes, which demonstrate diverse substrate tolerance, stability in organic solvents and at elevated temperatures [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Bioactive Indanes: Proof of Concept Study for Enantioselective Synthetic Routes to PH46A, a New Potential Anti-Inflammatory Agent

Zhang¹,

Scalabrino²,

Frankish

et al. 2018

Molecules

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PH46A is a single enantiomer and a member of the 1,2-indane dimer family. It has two contiguous stereogenic centers with S,S configurations, one of which being a quaternary center, which has been developed as a clinical candidate for the treatment of inflammatory and autoimmune conditions. The current synthetic route to PH46A involves the generation of an unwanted enantiomer (R,R)-7, thus reducing the final yield significantly. Therefore, we have investigated potential alternatives to improve the efficiency of this synthesis. The first phase of the study has demonstrated proof of principle for a chiral alkylation of ketone 3 using phase-transfer catalysis, providing a key intermediate ketone (S)-4. The parent alkaloids required for the synthesis of PH46A, quinine or cinchonidine, have also been identified. Promising enantiomeric excesses of up to 50% have been achieved to date, and the use of an alternative substrate, unsaturated ketone 9, has also opened up further avenues for optimisation in future studies. The second part of the study involved preliminary screening the effects of a panel of hydrolase enzymes on (rac)-4 in order to identify a potential chemo-enzymatic route to optimise the introduction of chirality into PH46A at early stage of the synthesis. The hydrolase module has also yielded positive results; enzyme AH-46 with MtBE providing a selectivity factor of 8.4 with enantiomeric excess of 77%. Overall, positive results were obtained in this proof of concept study described herein. It is believed that conditions of both chiral PTC alkylation and biocatalytic hydrolysis could be optimised to further enhance the selectivity and improve the overall yield. This work is currently ongoing.

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“…The hydrolase‐catalyzed esterification of alcohols is a well‐established transformation in modern organic chemistry and the cornerstone reaction in EKR of alcohol racemates. Over the years, several acyl donors (e.g., enol esters, anhydrides, trihaloesters) have been described in the literature to circumvent the unfavorable equilibrium in the condensation of alcohols and acids . Nonetheless, there are still some limitations, which requires the development of more cost‐effective and environmentally friendly acylating agents.…”

Section: Introductionmentioning

confidence: 99%

“…Another fundamental shortcoming is the laborious separation of each enantiomer, one as an alcohol and the other as an ester, obtained after the acylation reaction. Typically this separation involves a chromatographic step, which is especially undesirable for large‐scale processes . Several alternative methods have been reported, such as the use of nonconventional solvents (e.g., fluorous solvents, ionic liquids, eutectic mixtures, supercritical (sc) CO 2 ), polymer‐supported substrates, or distillation processes .…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Kinetic Resolution of Secondary Alcohols Using an Ionic Anhydride Generated In Situ

et al. 2016

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We developed a method for the resolution of secondary alcohols using an ionic anhydride acylating agent prepared directly in the reaction medium containing the biocatalyst Candida antarctica lipase B (CALB). NMR studies showed that mixing all components at the same time does not interfere with the coupling reaction or the enzymatic activity. After optimization of the reaction conditions, the method allowed the resolution of a number of substrates in very high conversions (46-48 %) and enantiomeric ratios (E>170) along with an easy recovery of both enantiomers without the need for preparative chromatographic separation. Additionally, both the starting ionic acid and the biocatalyst could be recovered and reused up to nine cycles without significant loss of enantioselectivity.

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Development of an Acid-Washable Tag for the Separation of Enantiomers from Bioresolutions

Cited by 22 publications

References 13 publications

Hyperpolarization of Amino Acids in Water Utilizing Parahydrogen on a Rhodium Nanocatalyst

Hyperpolarization of Amino Acids in Water Utilizing Parahydrogen on a Rhodium Nanocatalyst

Bioactive Indanes: Proof of Concept Study for Enantioselective Synthetic Routes to PH46A, a New Potential Anti-Inflammatory Agent

Enzymatic Kinetic Resolution of Secondary Alcohols Using an Ionic Anhydride Generated In Situ

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