Nitro-sugars

Other references to nitro-sugars appear in Chapters 14 and 21. 

Methyl 3-0-bcnzyl-4,6-0-benzylidene-2-deoxy-2-nitro-a-D-gIucopyranoside (157) has been prepared by oxidation of the corresponding oxime with trifluoro-peracetic acid (157) appears to adopt a twist-boat conformation (X,3 0 Hz) 

Takahashi, K. Takeda, M. Sakaguchi, N. Nimura, and II. Sakai, Hukusokan 

Kagaku Toronkai Koeu Yoshishu, Sth, 1975, 154 (Chern. Abs., 1976, 84, 150 881m). 

Treatment of methyl 2,3,4-tri-0-acetyl-6-deoxy-6-iodo-a-D-glucopyranoside with sodium nitrite and phloroglucinol gave the 6-deoxy-6-nitro-sugar, which was converted, via the a-bromide, into the corresponding adenin-9-yl nucleoside.  

A review has been published on the influence of configuration and conformation on the reactivity of nitro-derivatives of carbohydrates. A new naturally occurring nitro-sugar, L-rubranitrose (3-C-methyl-4-0-methyl-3-nitro-2,3,6-trideoxy-L-xj /o-hexose) (23) has been isolated from the hydrolysate of the antibiotic rubradirin.  

The recent literature on the synthesis and reactions of nitro-sugars has been re-viewed.  

Steric and electronic factors governing the addition of nucleophiles to methyl 4,6-0-benzylidene-2,3-dideoxy-3-nitro-P-D-eryt/iro-hex-2-enopyranoside (225) have been investigated. The addition of hydrogen cyanide, hydrazoic acid, and 

Other references to nitro-sugar derivatives are included in Chapters 8 and 13. 

Sakakibara, R. Sudoh, and T. Nakagawa, Bull. Chem. Soc. Japan, 1978, 51, 1189. 

A review on chemical reagents in photoaffinity labelling has reviewed die role of diazirino- ( azi- ) sugar derivatives. Disodium 3 -azibutyl a-D-mannopyranoside 6-phosphate and tetrasodium 2-azi-l,10-bis-(a-D-mannopyranosyloxy 6-phos-phate)-decane have been synthesis as photoaffinity probes for binding to mannose-6-phosphate receptors.  

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An additional stmctural feature found in everninomicin D is the presence of a nitro sugar residue, evernitrose (3) linked to ring B at C-12. Kverninomicins B (1), C (2), and 13-384 Component 1 (13) also have this unique nitro sugar. Chemical modification of the nitro group has led to the preparation of a number of highly active derivatives (6,7). 

The chemistry and biochemistry of nitro sugars and amino sugars have sdmnlated extensive research. They are the components of various andbiodcs, which show important biological... 

Vasella has used deoxy-nitro sugars for the synthesis of various biologically important carbohydrates, and the radical nitromethyladon of deoxy-nitro sugars has been used for synthesis of fnictose 6-phosphate" and 6-C-methyl and 6-C-rhydroxymethyl analogiies of iV-acetylnenraitinic acid fsee Scheme7.2. ... 

The conversion of oximes to nitro compounds have provided a useful method for the preparation of nitro sugars (see Eqs. 2.66-2.69)36,136 137 138... 

The reduction of nitro sugars with H2 in the presence of Raney Ni is one of the standard methods for the preparation of amino sugars (Eq. 6.47).93... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

More recently, the synthesis of relatively stable chiral acyl nitronates by the reactions of acetic anhydride and pyridine with secondary nitro sugar derivatives has been documented (221). 

This chapter reports the most relevant recent contributions in nitro sugar chemistry. It includes the following aspects preparation of nitro sugars, formation of carbon-carbon bonds and transformation of the nitro group into other functionalities. 

Nitro sugars are valuable compounds and synthetic intermediates of growing chemical interest that have been known for more than forty years. Thus, the first revision on nitro sugar chemistry was published in 19691 and the advances in this field during the seventies and the early eighties were reviewed in 1986.2... 

In the last twenty years, nitro sugars became powerful chemical tools on account of their usefulness for the construction of carbon-carbon bonds prior to the transformation of the nitro group into a variety of other chemical functionalities. As a result, a diverse range of funcionalized carbohydrates and other derivatives as carbasugars, cyclitols and heterocycles have been prepared. 

This chapter includes the most relevant recent contributions to the preparation and synthetic applications in nitro sugar chemistry. 

The importance of the chemistry and biochemistry of nitro sugars has sparkled a great interest in their preparation. Their synthesis was reviewed by Wade and Giuliano in 19905 and since then many synthetic efforts have been made to efficiently prepare several kinds of nitro sugars. 

Nitro sugars are mainly prepared by oxidation, nucleophilic substitution and aldol- or Michael-type condensations. 

Oxidation is a general method for the preparation of nitro sugars from other sugar derivatives, as amino or azido sugars and sugar oximes. 

Amino sugars can usually be oxidized to the corresponding nitro sugars using m-chloroperbenzoic acid (MCPBA).6 Thus, Kobertz et al. synthesized nitro sugar 2 from amino sugar 1 by treatment with MCPBA in 1,2-dichloroethane under reflux (Scheme l).7... 

Giuliano et al. have also reported a procedure for the oxidation of tertiary amino sugars to the corresponding nitro sugars, using ozone and OXONE as oxidizing agents (Scheme 3).10... 

Nitro sugars can also be prepared by oxidation of hydroxylamines. This strategy was used in 1999 by Nicolau et al. for the preparation of nitro sugar 9, a component of the natural occurring antibiotic everninomicin,11 that was obtained by ozonolysis of compound 8 followed by sequential treatment of the resulting compound with TFA and triphenylphosphine (Scheme 4). 

A nitro group can alternatively be introduced in a sugar by nucleophilic displacement of iodide by a nitrite ion. This procedure was recently used in the preparation of the L-idose derived nitro sugar 14, an intermediate in the synthesis of polyhydroxylated cispentacin analogues (Scheme 6).15... 

This approach to nitro sugars is limited to primary iodo sugars and gives poor results when the carbon bearing the iodo substituent is sterically hindered. 

Henry reactions of nitro sugars can be promoted by catalytic amounts of mild bases and it has widely extended the use of triethylamine. A recent example involves the condensation of sugar derived a,p-unsaturated aldehyde 15 with nitromethane in the presence of triethylamine, to give... 

Kambe and Yasuda19 discovered the effectiveness of the fluoride as a Henry reaction catalyst. Since then, the use of diverse fluorides is a common method to catalyze nitro aldol condensations, since they provide mild conditions that are particularly convenient for sensitive products as carbohydrates. The most common fluorides are potassium fluoride20 and tetrabutyl ammonium fluoride.21 A recent example relates to the TBAF catalyzed addition of nitroethanol to the D-glucose derivative 18, to give nitro sugars 19 (Scheme 8).22... 

However, this multistep procedure is experimentally complex. A simpler variation described in 199127 consists of the reaction of an aldehyde and a nitro compound in the presence of triethylamine, TBAF and tert-butyl-dimethylsilyl chloride. Under these conditions, nitro sugars are obtained in good yieds and higher diastereoselectivities than those afforded by the standard conditions. This procedure was used in several synthesis of 2-nitro-2-deoxyaldoses, as for the condensation of l,l-diethoxy-2-nitroethane and l,2 3,4-di-0-isopropylidene-a-D-galacto-hexodialdo-l,5-piranose.28 More recently, it was applied to the addition of ethyl nitroacetate to the D-glucose derived aldehyde 18, to give nitro sugar derivatives 26, key precursors of polysubstituted cyclohexane a-amino acids (Scheme 10).29... 

More recently, a similar transformation was used for the preparation of the nitro sugar derivative 32, a precursor of a carbohydrate mimic of 2-deoxystreptamine (Scheme 12).33... 

The Michael addition of nitroalkanes to sugar-based a,p-unsaturated carbonyl compounds is another powerful method for the preparation of nitro sugar derivatives. 

Michael addition of nitromethane to D-glucose based vinyl sulfone 38 to afford nitro sugars 39 and 40 was also recently described (Scheme 15).37... 

Henry reaction of nitro sugar 11 with formaldehyde allowed the introduction of two hydroxymethyl groups at the carbon bearing the nitro group, and hence opened a specific route for the preparation of branched-chain imino sugar 57 and analogues (Scheme 20).44... 

Thus, treatment of 11 with paraformaldehyde and TBAF in THF provided the novel branched-chain nitro sugar 54. Reduction of its nitro group to the amino group of 55 followed by deprotection of its anomeric position, resulted in the amine 56, that finally led to compound 57, the first reported branched-chain seven-membered imino sugar, after a synthetic sequence consisting of a reductive amination. 

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