Nitro sugars, synthesis

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. ... 

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). 

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. 

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... 

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... 

Michael additions to sugar nitro olefins have received considerable less attention than the Henry reaction involving nitro sugars. Early examples of Michael addition include the synthesis54 of licoricidin by Paulsen in 1982, the addition of phosphorous nucleophiles to a D-glucose based nitro olefin55 by Yamashita in 1987 and the synthesis of the natural antibiotic polyoxin published by Barret in 1990.56... 

A similar E1CB elimination of a nitro group in nitro sugars was involved in a recently reported synthesis of methyl 4,6-0-benzylidene-2,3-dideoxy-2-C-formyl-a-D-erH ro-hex-2-enopyranoside 163 (Scheme 49).107... 

A simple synthesis of a 7-membered aza sugar from the unsaturated aldehyde 4 was proposed by Moutel.8 The same aldehyde 4 was used in the synthesis of modified aza sugars such as 5 (Fig. 2) 9 An interesting approach to polyhydroxylated 7-membered branched aza sugars (e.g. 8) was proposed by Estevez.10 Nitro sugar 6 underwent the... 

H. H. Baer and K. S. Ong, Reactions of nitro sugars. IX. The synthesis of branched-chain dinitro sugars by Michael addition, Can. J. Chem. 46 2511 (1968). 

T. Sakakibara and R. Sudoh, Stereoselective synthesis of the thermodynamically less stable manno-isomers from a nitro sugar, Carbohydr. Res., 50 (1976) 191-196. 

T. Takamoto, R. Sudoh, and T. Nakagawa, Study on nitro sugars. Part II. Synthesis of benzyl 3,5-di-0-benzyl-2-deoxy-2-nitro-a-D-xylofuranoside and its transglycosylation with alkali, Carbohydr. Res., 27 (1973) 135-140. 

Addition of Pseudohalogens to Unsaturated Carbohydrates. Part III. Synthesis of 3-Deoxy-3-C-nitromethyl-D-allose, a Branched-chain Nitro Sugar, W. A. Szarek, J. S. Jewell, I. Szczerek, and J. K. N. Jones, Can.]. Chem., 47 (1969) 4473-4476. 

BAER FISCHER Amino sugar synthesis Synthesis o13-nitro and 3-amtno sugars by aWol condensation of sugar-derived dlaWehydes with nilroalkanes. 

Yunker, M B, Plaumann, D E, Fraser-Reid, B, The stereochemistry of conjugate addition of lithium dialkyl cuprate reagents to some carbohydrate a-enones. Can. J. Chem., 55, 4002-4009, 1977. Baer, H H, Ong, K S, Raeactions of nitro sugars. IX. The synthesis of branched-chain dinitro sugars by Michael addition. Can. J. Chem., 46, 2511-2517, 1968. 

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