5-Thio-D-xylose

Halo-sugars are very useful building blocks for designing further reactions by substitution of halogen atoms. From these compounds, we have developed a che-moenzymatic strategy giving 5-thio-D-xylose in four steps (the key step being catalyzed by FruA). 

FIGURE 9.10 5-Thio-D-xylose (11), l,5-anhydro-5-thio-D-mannitol (41). 

A de novo approach to 5-thio-D-f/ireo-2-pentulofuranose (5-thio-D-xylulose, 13) from 2-mer-captoacetaldehyde with the aid of rabbit muscle aldolase (RAMA, EC 4.1.2.13) as well as yeast transketolase (EC 2.2.1.1) was reported by Effenberger and co-workers [38]. This approach was recently extended in combination with the glucose isomerase (EC 5.3.1.5) catalyzed isomerization of compound 13 in an interesting synthesis [39] of 5-thio-D-xylose (4), a precursor for antithrombotic drugs [40]. 

Thio-D-xylose (4) was prepared by Adley and Owen [4], Scharz and Yule [5], as well as by Whistler and co-workers [9,10]. 

Scheme 10 Synthesis of 5-thio-D-xylose an

Thus, the reaction of l,2,3,4-tetra-0-(2-methylpropanoyl)-5-thio-D-xylose with SnCU in excess gave the mixture of azides 68 with p a = 2.3 1. It may be assumed that this outcome is influenced by the donor properties of the ring sulfur... 

Acetamido-3-deoxy-l,2 5,6-di-0-isopropylidene-P-L-idofuranose, A-292 3-Acetamido-3-deoxy-P-D-galactopyranose, A-207 3-Acetamido-3-deoxy-P-D-glucopyranose, A-267 3-Acetamido-3-deoxy-1,2-0 -isopropylidene-a-D-allofuranose, A-157 3-Acetamido-3-deoxy-l,2-0-isopropylidene-a-D-glucofuranose, A-267 3-Acetamido-3-deoxy-l,2-0-isopropylidene-a-D-gulofuranose, A-280 3-Acetamido-3-deoxy-l,2-0-isopropylidene-P-L-lyxofuranose, A-297 3-Acetamido-3-deoxy-5-thio-D-xylose, A-352... 

Hughes and his co-workers have reported the preparation of three types of thio-sugar derivatives. The strong preference of 5-thio-D-ribose and 5-thio-D-xylose for ring-closure on to sulphur is shown by the formation of the strained 1,2 3,4-diacetals (188) and (189) in the reactions with acetone and 2,2-dimethoxy-... 

Thio-D-xylose has been prepared in a similar manner [112]. 1,2-0-Isopropy-lidene-5-O-tosyl a-D-xylofiiranoside was reacted with the sodium salt of ben-zylthio alcohol, followed by reaction with sodium amide and acid (reaction 4.122). 

Ross and Ugi" prepared l-amino-5-deoxy-5-thio-2,3,4-tri-6)-isobutanoyl-P-D-xylopyranose 61a from xylose via the 5-desoxy-5-thio-D-xylopyranose. The U-4CRs of this amine form a-aminoacid derivatives stereoselectively and in excellent yields. These products have the advantage that their products are stable and their auxiliary group 5-desoxy-5-thio-D-xylopyranose can be cleaved off selectively by mercury(II) acetate and trifluoroacetic acid. The expected steric structure of the corresponding U-4CR product was confirmed by X-ray measurement. 

Solvent-free three-component Biginelli reactions of 2-phenyl-l,3-oxazol-5-one, D-xylose/D-glucose and (thio)ureas 136 in the presence of Ce2(S04)3 salt (10%) under microwave irradiation produced perhydropyrido[l,2-c] pyrimidines 137 and 138 with 94% trans diastereoselectivity (Scheme 3). In the absence of Ce3+ salt no reaction occurred, and without microwave irradiation using conventional heating at 90 °C yields were significantly lower (39-51%) even for longer reaction times (3-5 h). If shorter reaction periods (4-7 min) was applied addition products 139 could be isolated, which then were converted to pyrido[l,2-c]pyrimidines 137 (X = O, R = H) and 138 (X = S, R = Ph) (07SL1905). 

Prediction of the composition of the equilibrium mixture on the basis of presumed conformational stability or instability is uncertain, as is shown by the example of 2,5-bis(acetamido)-2,5-dideoxy-D-xylose, obtainable by periodate cleavage of 3,6-bis(acetamido)-3,6-dideoxy-D-gulopyranose. From the reaction mixture, 2,5-bis(acet-amido)-2,5-dideoxy-D-xylofuranose can be obtained crystalline in 36% yield no report was made as to any content of pyranose. Other 5-acetamido-5-deoxyxylose derivatives, for example, methyl 3,5-bis(acetamido)-2-S-benzyl-3,5-dideoxy-2-thio-/3-D-xylofuranoside," were not susceptible to hydrolysis. ... 

Thio-B-Xylose, 5-Thio-D-Glucose As early as 1965 the inhibitory activity of 5-thio-D-xylopyranose (4) against 8-D-xylosidases was observed and a fairly high K value of 2 mM was reported for this reversible inhibition [114]. 

Based on a wide range of crystallographic data of the mutant enzymes with D-xylose (18),5-thio-D-glucopyranose (38) or 5-deoxy-D-xylulose (39) (Scheme 15) in their active sites, this view was not supported by the investigators. An in-... 

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