Amide-linked sugars

An interesting example of a branched trimer containing (1 6)- and /3(1 2)-amide-linked sugars was supplied by Sicherl and Wittmann who devised mimetics of amino glycosides [37]. Pioneered by the group of Kessler [38] pyranoid sugar amino acid templates were described to represent turn mimetics and model peptides [39,40] including cyclic peptides [41,42]. As... 

We use sugar amino add as a fundional, sucdnct classification term, although a plethora of terms have been proposed in the literature for compounds derived from Saa. These include saccharide-peptide hybrids, glycosamino adds, peptidosaccharides, sac-charopeptides, amide-linked carbohydrates, and carbopeptoids, although the latter compounds most often do not have a peptoid functionality. In some cases Saa are linked to each other, in other cases to amino acids. 

With neuraminic acid, a sugar amino acid widely occurring naturally as Ai-acetylneuraminic acid, an amide-linked (1 5)-dimer 21 (O Scheme 6) and the corresponding 2,3-ene analogue were prepared [30], On a solid phase, even an octamer 22 was available [31]. 

Oligomerization of a 7-amino-2,6-anhydro-7-deoxy-heptonic acid results in mimetics of (1 6)-linked sugars with a three-atom instead of a two-atom linker. The sulfated tetramer 24 (O Scheme 7) turned out to exhibit /x-molar activity in the protection of MT2 cells from HIV infection [33], and was also shown to provide heparanase inhibitory activity [34]. With different location of the amide bond, a still benzyl protected /3(1 6)-linked octamer of glucosyl-uronic acid-methyl amine (Gum [35]) 25 was synthesized [36]. 

Carboranes are particular cyclic spacers that have been introduced for boron neutron capture therapy to be taken up by tumor cells [295,296,297]. Aromatic spacers have been integrated in cyclodextrin analogues to modify the guest binding properties [298,299,300]. Also amide-linked polymeric open chain sugars with aromatic spacers were prepared [257,264,301]. Sugars with cyclic spacers are also found in Nature [302], well known examples are antibiotics such as calicheamicin [303,304] or vancomicin [305]. 

In the late 1960s and into the mid-1970s new synthetic reports appeared in the literature. Most of these focused on the total synthesis of naturally occurring pyranosyl sugar amino acid conjugates. Then, in 1976, Fuchs and Lehmann published the first synthesis of sugar amino acids amidically linked in a fashion similar to a-amino acids. Surprisingly, this disclosure received little attention for nearly 20 years. 

In 1995 Nicolaou and coworkers initiated a renaissance in the construction of sugar amino acid conjugates with their synthesis of carbonucleotoids [49]. Although they did not prepare amide-linked carbohydrates, they did introduce the term carbopep-toid to designate such materials. Shortly thereafter, a number of papers directed toward the synthesis of carbopeptoids appeared. One of the earliest was reported by Wessel et al., who used nor-muramic acid derivatives and condensed them in solution by means of 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT) in DMF to construct a tetramer (Fig. 27). 

Starting from n-butyl (n-butyl a-o-mannopyranosiduronate) 4, uronamides 10 bearing a short butyl chain at the anomeric position and a longer alkyl (dodecyl, octadecyl, and oleyl) chain amide-linked to the sugar head were prepared following a one-step solvent-free procedure (Scheme 8). The aminolysis reaction was performed at 65°C to make the fatty amine liquid and under reduced pressure (3 mbar) to eliminate the butanol formed all through the reaction. To avoid significant... 

Hoffmann-La Roche Sugar modification 2, 6 -Amide-linked hexopyranosyl nucleotides WO9714709 1997... 

Boimd to 1, the intercalated bithiazole is positioned with its C-terminal thiazole ring sandwiched between Aio and An while the N-terminal thiazole occupies a more central position between the base pairs involving these same residues the helix is unwound by 8.9. In this position, the guanidinium tail is threaded through to the major groove and forms a water-mediated H-bond to the N7 of Aio. Connected to the bithiazole, the Thr-methylvalerate linker is well ordered and makes two specific H-bonds to the sugar-phosphate backbone these interactions include the methyl valerate hydroxyl group to the 03 of T6 and the bithiazole NH (amide link to Thr) to the 04 of T7. 

The chemical structure of lipid A of lipopolysaccharide isolated from Comamonas testosteroni was recently determined by lida et al. (1996) by means of methylation analysis, mass spectrometry and NMR. The lipid A backbone was found to consist of 6-0-(2-deoxy-2-amino-P-D-glucopyrano-syl)-2-deoxy-2-amino-alpha-D-glucose which was phosphorylated in positions 1 and 4. Hydroxyl groups at positions 4 and 6 were unsubstituted, and position 6 of the reducing terminal residue was identified as the attachment site of the polysaccharide group. Fatty acid distribution analysis and ES/MS of lipid A showed that positions 2,2, 3 and 3 of the sugar backbone were N-acylated or O-acylated by R-3-hydroxydecanoic acid and that the hydroxyl groups of the amide-linked residues attached to positions 2 and 2 were further O-acylated by tetradecanoic and dodecanoic acids, respectively. 

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