Nitrogen Inversion as a Diastereomeric Relay in Azasugar Synthesis: The First Synthesis of Adenophorine

Maughan, Michael A. T.; Davies, Ieuan G.; Claridge, Timothy D. W.; Courtney, Steve; Hay, Phil; Davis, Benjamin G.

doi:10.1002/anie.200351002

Cited by 60 publications

(34 citation statements)

References 52 publications

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“…Four years after the publication of the (-)-adenophorine synthesis by Maughan and co-workers, [13] we have performed the first total synthesis of naturally occurring (+)-adenophorine in 14 steps from the Garner's aldehyde enantiomer and in 3.5 % overall yield. We have once again exploited the synthetic potential of the trans-2,6-disubstituted 1,2,5,6-tetrahydropyridine key intermediate for the preparation of enantiomerically pure α-1-C-alkyl-iminosugars.…”

Section: Discussionmentioning

confidence: 98%

“…The absolute configuration of this (+)-iminosugar, isolated from Adenophora spp. by Ikeda and co-workers in 2000, [8] was determined three years later by optical rotation measurements performed on the (-) enantiomer synthesized by Davis et al [13] Iminosugars are frequently synthesized from carbohydrates as chiral pool starting materials with use of an amination-intermolecular cyclization sequence or an intramolecular reductive amination cyclization as the key step.…”

Section: Introductionmentioning

confidence: 99%

“…In 2000, Asano and co-workers isolated a series of α-1-C-alkylated analogues of 1,2-dideoxynojirimycin (fagomine) and 1-deoxy-homonojirimycin from Lobelia sessilifolia and Adenophora spp. [8,9] structural determination was accomplished by classical NMR ( 1 H and 13 C NMR) and mass spectroscopy studies (HRFABMS). Their inhibitory activities toward various glycosidases showed IC 50 values of around 30 µ with β-galactosidase (bovine liver) for the α-1-C-alkylated 1,2-dideoxy-iminosugar 4 ( Figure 1) and poor or no activity on α-glucosidase (rice), [9] whereas 1-deoxy-iminosugars such as α-1-deoxy-1-C-methylhomonojirimycin (named adenophorine, 5, Figure 1) was active on α-glucosidase (IC 50 : 34 µ) but not on β-galactosidase.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

First Total Synthesis of (+)‐Adenophorine, a Naturally Occurring Inhibitor of Glycosidases

Pearson¹,

Evain²,

Mathé-Allainmat³

et al. 2007

Eur J Org Chem

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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First Total Synthesis of (+)‐Adenophorine, a Naturally Occurring Inhibitor of Glycosidases

Pearson¹,

Evain²,

Mathé-Allainmat³

et al. 2007

Eur J Org Chem

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“…It has been shown that regioselective dehydrochlorination of N-chloropiperidine azasugars is controlled by the switchable configuration at the chloramine nitrogen atom. 53 The importance of detailed mechanistic and stereochemical insights in dehydrochlorination reactions has also been shown in the case of N-chlorinated macrolide antibiotics.…”

Section: -52mentioning

confidence: 97%

Base-catalyzed reactions of environmentally relevant N-chloro-piperidines. A quantum-chemical study

2011

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Electronic structure methods have been applied to calculate the gas and aqueous phase reaction energies for base-induced rearrangements of N-chloropiperidine, N-chloro-3-(hydroxymethyl)piperidine, and N-chloro-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine. These derivatives have been selected as representative models for studying the chemical fate of environmentally relevant chloramines. The performance of different computational methods (MP2, MP4, QCISD, B3LYP and B2PLYP) for calculating the thermochemistry of rearrangement reactions was assessed. The latter method produces energies similar to those obtained at G3B3(+) level, which themselves have been tested against experimental results. Experimental energy barriers and enthalpies for ring inversion, nitrogen inversion and dehydrochlorination reactions in N-chloropiperidine have been accurately reproduced when solvent effects have been included. It was also found that the combined use of continuum solvation models (e.g. CPCM) and explicit consideration of a single water molecule is sufficient to properly describe the water-assisted rearrangement of N-chlorinated compounds in basic media. In the case of N-chloro-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine, which represents the chlorinated metabolite of the antidepressant paroxetine, several different reactions (intramolecular addition, substitution, and elimination reactions) have been investigated. Transition state structures for these processes have been located together with minimum energy structures of conceivable products. Imine 4A is predicted to be the most stable reaction product, closely followed by imine 4B and oxazinane 8, while formation of isoxazolidine 7 is much less favourable. Calculated reaction barriers in aqueous solution are quite similar for all four processes, the lowest barrier being predicted for the formation of imine 4A.

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“…The first synthesis of (-)-adenophorine (6) [7] (nonnatural enantiomer) was achieved in 26 % yield in ten steps from the d-glucose derivative 114 by Davies et al [59] using an intramolecular Staudinger/aza-Wittig reaction, as presented in Scheme 14. The opposite optical rotation of the synthetic compound allowed the authors to assign the absolute configuration of natural (+)-adenophorine.…”

Section: Chiral-pool Starting Materials: Carbohydratesmentioning

confidence: 99%

Recent Advances in the Total Synthesis of Piperidine Azasugars

et al. 2005

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Since the discovery of nojirimycin, a glycosidase inhibitor, polyhydroxylated piperidines (also called azasugars: the ring O‐atom of a carbohydrate is replaced by nitrogen) have attracted considerable attention and have been the target of numerous synthetic strategies during the last decade. The efficient synthesis of naturally occurring azasugars and their analogs is of considerable importance due to their potential glycosidase inhibitor properties. Some of them have been widely investigated as candidates for drugs to treat a variety of carbohydrate‐mediated diseases such as diabetes, viral infections, including HIV, cancer metastasis, hepatitis, and Gaucher’s disease. This microreview focuses on recent syntheses of azasugars. In addition, the biology of these compounds is briefly considered. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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Nitrogen Inversion as a Diastereomeric Relay in Azasugar Synthesis: The First Synthesis of Adenophorine

Cited by 60 publications

References 52 publications

First Total Synthesis of (+)‐Adenophorine, a Naturally Occurring Inhibitor of Glycosidases

First Total Synthesis of (+)‐Adenophorine, a Naturally Occurring Inhibitor of Glycosidases

Base-catalyzed reactions of environmentally relevant N-chloro-piperidines. A quantum-chemical study

Recent Advances in the Total Synthesis of Piperidine Azasugars

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