Aza-sugar

Streith J., Defoin A. Aza Sugar Syntheses and Multi-Step Cascade Rearrangements Via Hetero Diels-Alder Cycloadditions With Nitroso Dienophiles Synlett 1996 189-200... 

Aqueous aza-Diels-Alder reactions of chiral aldehydes, prepared from carbohydrates and with benzylamine hydrochloride and cyclopentadiene, were promoted by lanthanide triflates (Eq. 12.65).137 The nitrogen-containing heterocyclic products were further transformed into aza sugars, which are potential inhibitors against glycoprocessing enzymes. 

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... 

Synthesis of bicyclic aza sugars from D-xylose was reported. A key step involved reaction of the nitrone 9 with ethyl acrylate providing intermediate 10, which was finally converted into aza sugars (Fig. 4).11... 

The 1,3-dipolar cycloaddition of nitrone 12 (derived from D-glucose) was also used for the preparation of bicyclic aza sugars of type 14 (route a Fig. 5).12 Another classical approach (route b) allowed to prepare the analogs (e.g. 17).13,14... 

Fig. 5 Dipolar cycloaddition route towards bicyclic aza sugars.

Interesting structural variation of target aza sugars was initiated from compound 18, readily available in a few standard steps from methyl glucoside (Fig. 6).15... 

A-allylamine 23 (obtained by standard transformations of 6-iodogluco-side 22) underwent cyclization into the monocycle 24. However, when the amine was in situ protected as a Boc derivative it could be subjected to the RCM process. The products were further converted into the bicyclic aza sugar 26.19 A similar approach to eight-membered ring aza sugars was recently reported (Fig. 9).20... 

Fig. 9 Application of RCM in the synthesis of eight-membered ring aza sugars.

Fig. 12 Synthesis of a simple aza sugar based on mercuration of its unsaturated precursor.

Similar derivatives (formally being C-disaccharides with the normal and aza sugar rings) were prepared by Vogel (Fig. 37).52... 

Application of simple sugars as starting materials for the preparation of optically pure complex products represents nowadays the classic methodology of organic synthesis it is covered by many comprehensive reviews, cited here only in references.88 These references provide the precise state-of-art in the synthesis of aza sugars, carbasugars and other derivatives. 

DHAP-Dependent Aldolases in the Core of Aza Sugar Synthesis... 

Another stereoselective synthesis (Scheme 11) is based on sugar aldehyde 35 and intermediate 36 subsequent 1,2-O-isopropylidine deprotection, N,0-debenzylation/olefin reduction/reductive cyclization in a single pot, and O-acetylation result in the formation of bicyclic aza sugar 37 (09TA1217). 

V. Notenboom, S. J. Williams, R. Hoos, S. G. Withers, and D. R. Rose, Detailed structural analysis of glycosidase/inhibitor interactions Complexes of Cex from Cellulomonas fimi with xylobiose-derived aza-sugars, Biochemistry, 39 (2000) 11553—11563. 

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