Azides anomeric

Our first synthesis of a polymer-bound anomeric amine involved a trisaccharide model system (Scheme 2.20).45 Disaccharide 66 was extended in standard fashion to trisaccharide 67 and fully protected to give 68. This latter compound was treated with anthracenesulfonamide and Jt.vy/u-coll )2C104 to form the intermediate 69. Reaction of the iodosulfonamide 69 with tetra-n-butylammonium azide followed by acetylation provided the anomeric azide 70. 

Tejima et al. [218] found that partial tosylation of the 1,6-anhydrolactose derivative (310) gave the 2-0-tosyl derivative (311) in 25 % yield and this was converted into the epoxide (312) which could be converted into the anomeric azides (313) and hence into A-acetyllactosamine. Tejima et al. [219] have also prepared peracetyl lactosamine from the 1,6-anhydro derivative (314). 

Unverzagt C, Kunz H, Stereoselective synthesis of glycosides and anomeric azides of glucosamine, J. Prakt. Chem., 334 570-8, 1992. 

In another interesting reaction, 2-azido-2-deoxypyranosyl fluoride 136 is obtained from the 2-OH unprotected mannosyl azide 135, by DAST-mediated displacement involving neighboring group participation and migration of the anomeric azide group (O Scheme 62) [101]. 

The 1,2-trans azide 16 ean be obtained in crystalline form from 6-0-acetyl-3-azido-2,4-dibenzamido-2,3,4-trideoxy-a-D-glucopyranosyl chloride with LiNs in DMF." ° Both the acetylated anomeric azides of 2-deoxy-a-D-araZ)/ o-hexopyran-ose can be obtained by this approach however, reaction of the a-bromide 17 with azide must be performed at 5 °C, affording the inversion product 18 in excellent yield. Curiously, formation of the anomeric azide 20 from the bromide 19 was reported in only 45% yield. " ... 

In recent years, the Lewis acid-catalyzed azidation of protected sugar derivatives has been extended to more-complex starting materials. For instance, isopropyli-dene-protected ketose derivatives were treated with trimethylsilyl azide and a catalyst to give various ketosyl azides.Thus, the reaction of 6-O-tert-huX.-yldimethylsilyl-l,2 3,4-di-(9-isopropylidene-p-D-psicofuranose (90) gave a mixture of partially deprotected anomeric azides 91-94 in 54% overall yield. The corresponding transformation of 3-deoxy-l,2 4,5-di-(9-isopropylidene-p-D-erjr/zro-hex-2-ulopyranose (95) led to the azide mixture 96 in 75% yield.2,3,4,6-Tetra-... 

All of these methods suffer from undesired side reactions, the need to do difficult purification sequences, the need to synthesize the anomeric azide or amine, low yields of product or a loss of anomeric stereocontrol in the reaction. 

Williams et al. reports that l-(2,3,4,5-tetra-0-benzyl-p-D-glucosyl)-3,4,5,6-tetrafluoro-l-H-benzo[d][l,2,3]-triazole 136 can be prepared from available anomeric azide and 2-amino-3,4,5,6-tetrafluorobenzoic acid through click methodology [118],... 

The great potential of CuAAC for glycoconjugate synthesis was enhanced by Shoda s method for the direct preparation of sugar anomeric azides... 

SCHEME 6.11 Synthesis of Cj- and C2-symmetric oligosaccharide macrocycles starting from anomeric azide with 4-propargyl ether at the opposing terminus. 

A library of a-D- and P-D-glucopyranosyl triazoles 38-41 have been developed utilizing copper click (Scheme 6.12). An interesting fact observed in this synthesis is that the P-anomeric azide 5 takes 10-45 min to complete the reaction, whereas a-anomeric azide 37 requires 45 -120 min under similar conditions. Difference in reaction rates was correlated with the anomeric effect on the dipole character of the anomeric azides [28]. 

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