Acyl disaccharides

In 1963, a series of systematic studies was begun on the reaction of fully acylated disaccharides (acetates and benzoates) with methanolic or aqueous solutions of ammonia at room temperature. Octa-O-acetyl-a-cellobiose in 16% methanolic ammonia afforded44 1,1-bis-(acetamido)-l-deoxycellobiitol (45) and N-acetyl-a-cellobiosylamine (46), which is the anomer of the cellobiosylamine previously described by Zechmeister and Toth41 and Micheel and coworkers.43... 

Table IV (see p. 132) shows the products and yields obtained from the ammonolysis of acylated disaccharides.

Derivatives from the Reaction of Ammonia with Acylated Disaccharides... 

The next step of our synthetic study was the preparation of 1- and/or 4 -phosphates of the acyl disaccharide because it seemed to be important to have both the 1- and 4 -monophosphates and the 1,4 -diphosphate in order to know the role of both phosphate moieties for activities. Though we first attempted the direct and simultaneous phosphorylation of the 1- and 4 -hydroxyl groups in Q, this could not be achieved under various conditions. The two phosphate moieties were therefore introduced separately, using different procedures (4). 

Synthesis of acyl disaccharides containing (R)-3-hydroxytetra-decanoyl moieties... 

Figure 9. Synthesis of di-N-acyl disaccharide derivatives via the oxazoline route.

By the sequential use of different enzymes, efficient synthesis of partially acylated disaccharides can be achieved. 6-0-acetyl glucal 5 (Scheme 4), prepared... 

An acylated disaccharide 75 was efficiently prepared using polymer-supported reagents. Formation of glycosyl imidate 72 was carried out with Dowex 1-8X (OH form) as a polymer-supported base, and glycosylation of acceptor 73 with the imidate 72 was carried out using... 

LPS and lipid A derivatives EPS is a component of the membrane of Gram-negative bacteria, with lipid A, the central poly-acylated disaccharide, as the main active part. Since EPS is highly toxic, derivates with reduced toxicity have been developed, one of them is monophospholipid A (M PE), a mucosal adjuvant supporting humoral and cellular response [32]. 

A monoterpene glycoside isolated from the fruits of Gymnocladus chinensis has been shown to contain the acylated disaccharide -0- -D-glucopyranoeyl-4-0-(2-methylbutanoyl)-et.L-arablnosyl moiety. 

Lipid A is a category of complex hexa-acylated disaccharide of glucosamine in bacteria. The existence of Lipid A metabolism pathway in plants was demonstrated by LC-MS [28], The structure of the Lipid A-related compounds is confirmed by product-ion analysis utilizing QqTOF-MS [28]. 

Another advantageous feature of enzymes in an esterification reaction lies in their ability to distinguish a specific hydroxyl group of a complex polyalcohol like sugar derivatives. KUbanov et aL found that Bacillus subtilis protease (subtilirin) catalyzes the regioselective acylation disaccharides 16, as well as nucleosides and related compounds in N,N-dimethylformamide [40]. 

Most of the anthocyanins acylated with caffeic acid have this cinnamyl moiety linked to a glucosyl position 6, as in gooseberries, some grape cultivars, ° " ° black carrots, red cabbage,red radishes," and sweet potatoes. Some anthocyanins isolated from species of potatoes have a caffeyl group located at position 4 of the rhamnosyl unit of the rutinose disaccharide. " ... 

A typical procedure calls for reaction of the hemiacetal donor with dicydohexyl carbodiimide and copper(I) chloride (0.1 equiv) at 80 °C, followed by an addition of the acceptor and continued heating. As an early demonstration of this protocol, oc-riboside 86 was prepared in moderate yield but with exclusive stereoselectivity [141]. Further measures were required for the glycosylation of monosaccharide acceptors, such as addition of p-toluenesulfonic add (0.1 equiv) to promote the formation of disaccharide 87 [144]. The method was more suitably applied to the synthesis of O-acyl glycopeptides, as evidenced by the formation of 88 in 60% yield [143,144]. Various peptides with non-nudeophilic side chains were found to be amenable to this stereoselective reaction. The [3-selectivity was suggested to arise from a preponderance of the a-isourea intermediate 85 in the activation step. 

Kusumoto and coworkers have found that the treatment of hemiacetal 1 with trifluoro- or trichloroacetic anhydride 94 (1 equiv) and trimethylsilyl perchlorate (0.2 equiv) selectively provides the corresponding anomeric ester intermediate 91 [152], Hemiacetal acylation occurs even in the presence of the alcohol acceptor. With Lewis acid assistance, the glycosyl ester intermediate is displaced to provide disaccharide products in good yields. This transformation allowed the synthesis of disaccharides 98 (81%) and 99 (91%). In some cases, acetic anhydride has been used as the electrophilic activator of hemiacetal donors and the reaction with thiol acceptors yields S-linked glycosides [153,154],... 

As these results and Fig. 2 show, three structural components may be defined in lipid A (/) the lipid A backbone consisting of a pyranosidic HexN disaccharide and phosphate groups, (ii) substituents of the backbone phosphate residues (polar head groups), and (iii) fatty acids. Therefore, lipid A of different bacteria may be classified according to the nature of the backbone constituents (GlcpN or GlcpN3N), the type and nature of the polar head groups, and features of the acylation pattern. In a few instances, other backbone substituents have been encountered. These will be described later in conjunction with individual lipid A forms. 

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