Glucose derivatives syntheses

Lipid A Analogues. - Of a set of eleven new JV-acylated L-serine-containing 2-amino-2-deoxy-D-glucose derivatives synthesized as Lipid A analogues and evaluated as synthetic immunoadjuvants, compound 78 had the greatest... 

For the synthesis of D-glucuronic acid, methods of oxidation of suitable D-glucose derivatives have been devised during the past two decades these procedures have been comprehensively reviewed by Marsh,6 Mehltretter,7 and Heyns and Paulsen.8 For special purposes, for example, for the preparation of 6-I4C-labelled D-glucuronic acid, chain-extension reactions of 1,2-O-isopropylidene-a-D-xy/o-pen-todialdo-I,4-fiiranose by the cyanohydrin synthesis9 or by ethynyla-tion10 are used, but these frequently yield mixtures of D-glucuronic acid and L-iduronic acid. 

A substantial amount of research has been carried out in the field of tetrazole-fused sugars (rhamnose, mannose, and glucose derivatives) - mostly because of the biological importance of these derivatives. In many of these cases synthesis of the fused tetrazole moieties has been perfected by intramolecular 1,3-cycloaddition reactions with participation of a cyano and azido group. Some of these results are shown in Schemes 26 and 27. 

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... 

Novel highly functionalized dipeptide isosters were synthesized via diastereoselective alkyl-arylation protocol of a glucose-derived (R)-tert-butanesulfinylimine. One of these novel sugar amino acid derivatives, a D-Ala-Ser/Thr isostere, was applied in a peptide synthesis protocol to afford a cyclic tetramer (Fig. 53).69... 

In common with cholesterol synthesis described in the next section, fatty acids are derived from glucose-derived acetyl-CoA. In the fed state when glucose is plentiful and more than sufficient acetyl-CoA is available to supply the TCA cycle, carbon atoms are transported out of the mitochondrion as citrate (Figure 6.8). Once in the cytosol, citrate lyase forms acetyl-CoA and oxaloacetate (OAA) from the citrate. The OAA cannot re-enter the mitochondrion but is converted into malate by cytosolic malate dehydrogenase (cMDH) and then back into OAA by mitochondrial MDH (mMDH) Acetyl-CoA remains in the cytosol and is available for fatty acid synthesis. 

By 1920, it was recognized that a successful chemical synthesis would probably require the use of a D-fructose maintained in the proper cyclic structure by the presence of substituents. The substituent groups would have to be stable enou to survive the conditions required in condensation with a suitable D-glucose derivative, but at the same time be capable of ready removal by agents that failed to affect any sucrose... 

D. E. Plaumann, B. J. Fitzsimmons, B. M. Richie, and B. Fraser-Reid, Synthetic route to 6,8-dioxabicyclo[3.2.1]octyl pheromones from D-glucose derivatives. 4. Synthesis of (—)-multistriatin, J. Org. Chem. 47 941 (1982). 

A classical selective reaction, described by Fischer and Armstrong,166 in which 6-bromo-6-deoxy-2,3,4-tri-0-acetyl-a-D-glucopyranosyl bromide (LXXXIX) is obtained from 0-D-glucose pentaacetate and liquid hydrogen bromide, has had application in the synthesis of 6-substituted D-glucose derivatives. The action of liquid hydrogen chloride on D-glu-cose has been studied by Hess, Strieker and Rutkowski,168 who have postulated a 1,1-chlorohydrin (XC) as an initial intermediate of the reaction. 

Scheme 51 Stereoselective synthesis of spiro-(3-lactams using D-(+)-glucose derived chiral ketenes...

Deshmukh et al. [134] have investigated the use of D-(+)-glucose derived chiral ketenes in the stereoselective synthesis of spiro-(3-lactams 226-227. The D-(+)-glucose acid chloride 224, serving as a ketene precursor, in the Staudinger cycloaddition reaction with appropriate imines 225 afforded the diastereomeric mixture of spirocyclic-(3-lactams 226-227 in 70 30 ratio, respectively. This reaction has cleanly produced only two diastereoisomers instead of theoretically possible four... 

We began our synthesis by finding the optimum reaction conditions for the catalytic asymmetric cyanosilylation of ketone 28 (Table 1). Based on previous studies,30 the titanium complex of a D-glucose derived ligand (catalyst 32 or 33) generally gives (/ )-ketone cyanohydrins, which is required for a synthesis of natural fostriecin. 

It has been reported that some simple, synthetic glycollpids, such as II-fatty acylated 2-amino-2-deoxy-D-glucose derivatives, exhibit potent immunostimulatory activities (5). We first examined a facile preparation of N-fatty acylated 2-amino-2-deoxy-D-glucopyranosides, which would be key intermediates for the synthesis of lipid A and its analogs (Figure 2). For this purpose, the one-step glycosylation catalyzed by ferric chloride (6, 7) was employed. 

P. Y. Goueth, G. Ronco, and P. Villa, Synthesis of ether-linked di- and trisaccharide derivatives. 1. Synthesis of disaccharides from 5,6-anhydro-D-glucose derivatives, J. Carbohydr. Chem., 13 (1994) 679-696. 

Triphenylmethyl (trityl) ethers of 2-amino-2-deoxy-D-glucose derivatives are formed with the primary C6-hydroxyl group, and they are useful intermediates in synthesis,6-166-178 being readily removed by hydrogen-olysis. 

To be presented in the sequel, are a series of prototype reaction channels leading from simple, tautomerically fixed D-glucose derivatives to enantiopure building blocks along preparatively useful, practical protocols, followed by their utilization for the straightforward total synthesis of a series of natural and nonnatural products in optically active, enantiomerically homogeneous form. 

Epimerization of alpha-configuration of 10 into a p-equatorial configuration through acidic treatment and decomplexation by iodine provided the pseudo enantiomeric form of D-glucose derivative 11 (5). Finally, 11 is converted into the hetero olefin 12 which then received a variety of nucleophiles by chelation control to accomplish the synthesis of segment C of TTM 13. 

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