Enantioselective syntheses and X-ray structures of (S)- and (R)-N-norlaudanidine: trace opium constituents

Zein, Ahmed L.; Dakhil, Otman O.; Georghiou, Paris E.

doi:10.1016/j.tetlet.2009.10.114

Cited by 14 publications

(14 citation statements)

References 17 publications

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“…Initially the stereoselectivity of norcoclaurine 3 produced using Cj NCS2 was investigated. Racemic 3 and ( S )‐ 3 (>80% ee by chiral HPLC of N ‐Boc‐ 3 and Mosher’s derivatisation) standards were synthesised using a phosphate‐mediated reaction, and by modification of a published procedure using a chiral auxiliary Bischler–Napieralski cyclisation and reduction strategy (see the Supporting Information) 11,12. These were reacted with ( R )‐MTPA chloride.…”

Section: Resultsmentioning

confidence: 99%

“…The chemical synthesis of chiral BIAs is often challenging as it requires the regioselective functionalisation of phenols and amines, and the formation of cyclic structures in a stereocontrolled manner 8–10. Despite the development of elegant chemical strategies for their production, syntheses of THIAs remain either step‐intensive or lack stereocontrol to generate single isomers 9,11,12…”

Section: Introductionmentioning

confidence: 99%

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The Catalytic Potential ofCoptis japonicaNCS2 Revealed – Development and Utilisation of a Fluorescamine‐Based Assay

et al. 2012

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The versatility and potential of a norcoclaurine synthase (NCS) from Coptis japonica NCS2 has been investigated, together with the development and application of a novel fluorescence-based high-throughput assay using nearly forty amines/aldehydes. The stereocontrol exerted by CjNCS2 on selected non-natural substrates has been determined, where the tetrahydroisoquinolines (THIAs) were formed as the (1S)-isomer in > 95% ee, as observed with the natural product norcoclaurine. Docking calculations involving THIA mechanism intermediates, utilising the reported Thalictrum flavum NCS X-ray crystallographic structure, were carried out and com-bined with the CjNCS2 screening results to further understand the mode of action of NCS. These findings suggested that in addition to the key active-site residues K122 and E110, D141 is also mechanistically essential for the enzymatic transformation. The exceptional tolerance of NCS towards aldehyde substrates is furthermore supported by our proposed mechanism in which the aldehydes protrude out of the enzymatic pocket.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Catalytic Potential ofCoptis japonicaNCS2 Revealed – Development and Utilisation of a Fluorescamine‐Based Assay

et al. 2012

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“…The synthesis of racemic 1-substituted tetrahydroisoquinolines 1 usually relies on one out of three different strategies: (i) formation of the C1–C8a bond of the isoquinoline core employing either the Pictet–Spengler( 20 ) or the Bischler–Napieralski( 21 ) cyclization, (ii) alkylation at position C1 of the isoquinoline via nucleophilic or electrophilic activation,( 22 ) and (iii) formation of the C4–C4a bond by a Pomeranz–Fritsch reaction (Scheme 2 ). ( 23 ) The first two approaches are particularly appealing since the target molecule is disconnected at central bonds leading to simple starting materials.…”

Section: Resultsmentioning

confidence: 99%

Biocatalytic Organic Synthesis of Optically Pure (S)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids

et al. 2011

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A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C–C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4–8 linear steps using either a Bischler–Napieralski cyclization or a C1–Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5–9 linear steps.

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“…Georghiou et al , employed ( S )- and ( R )-α-methylbenzylamines 381 and acid chloride 382 for the synthesis of ( S )- and ( R )- N -norlaudanidine ( 385 and ent - 385 ), a minor opium alkaloid, which was further transformed into tetrahydroprotoberberine alkaloids: ( S )-corytenchine ( 386 ) and ( S )-tetrahydropalmatrubine ( 387 ).…”

Section: Bischler–napieralski Cyclization/reductionmentioning

confidence: 99%

Asymmetric Synthesis of Isoquinoline Alkaloids: 2004–2015

2016

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In the past decade, the asymmetric synthesis of chiral nonracemic isoquinoline alkaloids, a family of natural products showing a wide range of structural diversity and biological and pharmaceutical activity, has been based either on continuation or improvement of known traditional methods or on new, recently developed, strategies. Both diastereoselective and enantioselective catalytic methods have been applied. This review describes the stereochemically modified traditional syntheses (the Pictet-Spengler, the Bischler-Napieralski, and the Pomeranz-Fritsch-Bobbitt) along with strategies based on closing of the nitrogen-containing ring B of the isoquinoline core by the formation of bonds between C-N, N-C, C-N/N-C, and C-N/C-C atoms. Methods involving introduction of substituents at the C1 carbon of isoquinoline core along with syntheses applying various biocatalytic techniques have also been reviewed.

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Enantioselective syntheses and X-ray structures of (S)- and (R)-N-norlaudanidine: trace opium constituents

Cited by 14 publications

References 17 publications

The Catalytic Potential ofCoptis japonicaNCS2 Revealed – Development and Utilisation of a Fluorescamine‐Based Assay

The Catalytic Potential ofCoptis japonicaNCS2 Revealed – Development and Utilisation of a Fluorescamine‐Based Assay

Biocatalytic Organic Synthesis of Optically Pure (S)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids

Asymmetric Synthesis of Isoquinoline Alkaloids: 2004–2015

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