Synthesis of D-erythrose and D-threose derived nitrones and cycloadditions to styrene

Kubáň, Juraj; Blanarikova, Iva; Fišera, Ľ.; Jaroskova, L.; Fengler‐Veith, M.; Jäger, Volker; Kožı́šek, Jozef; Humpa, Otakar; Prónayová, Naďa; Langer, Vratislav

doi:10.1016/s0040-4020(99)00512-8

Cited by 24 publications

(9 citation statements)

References 26 publications

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“…9 During recent years we have gained knowledge of the preparation of optically active nitrone templates for the asymmetric 1,3-dipolar cycloadditions and samarium diiodide-induced couplings. [21][22][23][24][25][26][27] In connection with our synthetic studies on the utility of chiral nitrones for the synthesis of biologically interesting compounds, we have prepared the sugarderived nitrones 2-8 possessing structures suitable for building nitrogen-containing heterocycles (Scheme 1). The aim of the present account is to describe the diastereoselective synthesis of isoxazolidinyl nucleosides by means of a 1,3-dipolar cycloaddition of chiral sugar-derived nitrones as the key step.…”

Section: Figurementioning

confidence: 99%

From sugars to modified nucleosides

Hýrošová¹,

Fišera²,

Medvecký³

et al. 2008

Arkivoc

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Two strategies are reported for the diastereoselective synthesis of isoxazolidinyl nucleosides, as potential antiviral agents -a one-step approach based on 1,3-dipolar cycloaddition of sugarderived nitrones with vinyl nucleobases derived from uracil and adenine, as well as a two-step methodology based on the Vorbrüggen nucleosidation of the 5-acetoxyisoxazolidines. The 1,3-dipolar cycloadditions of sugar-derived nitrones with vinyl acetate proceed with very good diastereoselectivity to give the diastereoisomeric isoxazolidines. Condensation of the major diastereomerically pure acetoxyisoxazolidines with silylated uracil, thymine, cytosine, Nacetylguanine and purines occurs with moderate to excellent stereoselectivity with the formation of the expected isoxazolidinyl nucleosides. The stereoselectivity of the addition of the silylated nucleobase is dependent on the structure of the substituent at C-3 originating from the starting chiral nitrone and on the attacking nucleobase.

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Section: Figurementioning

confidence: 99%

From sugars to modified nucleosides

Hýrošová¹,

Fišera²,

Medvecký³

et al. 2008

Arkivoc

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“…4 With our continuing efforts to utilize chiral 1,3-dipolar cycloadditions, 5 and with the goal of developing a simple route to the synthesis of polyhydroxylated derivatives of pyrrolizidines, 6 which have been shown to display antiviral activity, 7 via an asymmetric 1,3-dipolar cycloaddition we have recently published the preparation of new D-erythrose-1a and D-threose-6a derived nitrones and the stereoselectivity of their cycloadditions to styrene. 8 We now report the stereoselectivity of the cycloaddition of chiral sugar-derived nitrones 1a-c, 6a and 6b with methyl acrylate.The results are presented in the Table. In all cases the reactions were highly regiospecific, leading to the formation of diastereomeric isoxazolidines 2-5 (Scheme 1) and 7-10 (Scheme 2) as a mixture of three or four diastereoisomers in a good overall yield. 9 Purification by flash chromatography allowed the isolation of the pure major diastereoisomers 2a-c, 7a and 7b, while the isolation and/ or characterization of minor isomers was possible only for some of them.…”

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confidence: 91%

Stereoselectivity of 1,3-Dipolar Cycloadditions of d-Erythrose and d-Threose Derived Nitrones with Methyl Acrylate

Kubáň¹,

Kolarovič²,

Fišera³

et al. 2001

Synlett

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1,3-Dipolar cycloadditions between the D-erythrose and D-threose derived nitrones and methyl acrylate proceed in a regiospecific manner to afford the corresponding 3,5-disubstituted diastereomeric isoxazolidines in good yields. The stereoselectivity was dependent on the steric hindrance of the nitrone. The major products were found to have the C-3/C-4´ erythro and C-3/C-5 cis relative configuration. Its formation can be rationalized by less hindered endo attack of the Z-nitrone in an antiperiplanar manner with respect to the largest group of the cyclic acetal.The nitrone-olefin 1,3-dipolar cycloaddition is a powerful reaction in that it can create as many as three new contiguous stereogenic centres in a single step. 1 Based on an evaluation of the nitrone cycloaddition, it was felt that the stereochemistry of these new centers could be controlled if the reaction system were properly designed. 2,3 Regioand stereoselective nitrone cycloaddition, followed by reduction of the N-O bond to produce both an amino and a hydroxy function, allows the synthesis of many products of potential interest. 4 With our continuing efforts to utilize chiral 1,3-dipolar cycloadditions, 5 and with the goal of developing a simple route to the synthesis of polyhydroxylated derivatives of pyrrolizidines, 6 which have been shown to display antiviral activity, 7 via an asymmetric 1,3-dipolar cycloaddition we have recently published the preparation of new D-erythrose-1a and D-threose-6a derived nitrones and the stereoselectivity of their cycloadditions to styrene. 8 We now report the stereoselectivity of the cycloaddition of chiral sugar-derived nitrones 1a-c, 6a and 6b with methyl acrylate.The results are presented in the Table. In all cases the reactions were highly regiospecific, leading to the formation of diastereomeric isoxazolidines 2-5 (Scheme 1) and 7-10 (Scheme 2) as a mixture of three or four diastereoisomers in a good overall yield. 9 Purification by flash chromatography allowed the isolation of the pure major diastereoisomers 2a-c, 7a and 7b, while the isolation and/ or characterization of minor isomers was possible only for some of them. 10 When, methyl acrylate was used instead of styrene, 8 selectivity decreased. Only 48% of major diastereomer 2a for nitrone 1a (Table, entry 1) versus 81% in the case of styrene as dipolarophile 8 was deemed unacceptable. The usefulness of the chiral 1,3-dipolar cycloaddition depends on the diastereoselectivity achieved, since the major diastereoisomers 2a will be used subsequently for the synthesis of pyrrolizidines 11. 11 In light of these differences; we undertook a systematic study of the possibility to influence the selectivity of the cycloaddition. Our objective was the study of diastereoselectivity of cycloadditions stemming from the nitrone part. In the case of the cycloadditions with styrene we have found, that the stereoselectivity of the cycloaddition was influenced by the steric hindrance of both the N-and C-substituent of the nitrone, i.e. the selectivity increases as the nitrogen ...

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“…1 Based on an evaluation of the nitrone cycloaddition, it was felt that the stereochemistry of these new centers could be controlled if the reaction system was properly designed. 1-3 With our continuing efforts to utilize chiral 1,3-dipolar cycloadditions, [4][5][6][7] and with the goal of developing a simple route to the synthesis of proteinogenic and non-proteinogenic amino acids 8 via an asymmetric 1,3-dipolar cycloaddition we have chosen some α-amino acid -derived nitrones 3-8 as template for a nitron cycloaddition. Diastereoselective synthesis of β,γ,-diamino acids has received considerable attention, this is due to wide range of biological activities of these compounds e. g. emericedines A (1a), B (1b) and C (1c) -inhibit long chain fatty acid oxidation, aminostatine (2) -substrate analogue of statine led to potent aspartyl proteinase inhibitor of humane renine.…”

Section: Introductionmentioning

confidence: 99%