A -Methyl-maltoside

Scheme 15 Tandem iron(iii) chloride-catalyzed regioselective protection of silylated a,a-D-trehalose 60 and a-methyl maltoside 64. Procedure A FeCl3 6H2O, 5 mol%, PhCHO, 6 equiv Et3SlH, 2.2 equiv CH2CI2/CH3CN 4/1 0 °C to rt 3 h.

Adding an excess of acetic anhydride (10 equiv) and 5 mol% of FeCla SHaO furnished the expected 2,2 -di-0-acetylated a,a-D-trehalose 62 in an isolated 41% yield. The one-pot bis-reductive benzylidene ring opening required the successive addition of 10 equiv of EtsSiH and 15 mol% of the catalyst to afford the expected compound 63 in a moderate overall yield of 28%. Finally, the iron(iii) chloride-catalyzed tandem protocol was also successfully applied to a non-symmetric disaccharide. Per-O-silylated-a-methyl maltoside 64 was cleanly converted to the mono-benzylidene bis-ben l derivative 65 (Scheme 15). However, a higher loading of the catalyst (15 mol%) was required to reach 51% yield. 

It is possible to estimate how much of the measured optical rotation is in fact associated with the glycosidic linkage (Rees and Thom, 1977). Knowing the optical rotations of the two monomers, and of the molecule in the crystal state, then measurement of the optical rotation in solution makes it possible to calculate how much of that is due to the two angles and what is likely to be the configuration of the molecule in solution. The results are shown in Table 1. A Monte Carlo simulation in vacuo predicts a value of -28 for maltose and a-methyl-maltoside. This is very close to the experimental values in dimethyl sulphoxide and dioxan. For aqueous solutions there is absolutely no correspondence with the calculated value. The rotation is even of the opposite sign. 

Hehre and coworkers showed that beta amylase from sweet potatoes, an inverting, a-specific exo-(l 4)-glucanase, catalyzes the hydrolysis of jS-maltosyl fluoride with complex kinetics which indicated the participation of two substrate molecules in the release of fluoride ion. Furthermore, the reaction was strongly accelerated by the addition of methyl ) -maltoside. Hydrolysis of a-maltosyl fluoride, on the other hand, obeyed Michaelis-Menten kinetics. The main product with both a- and yj-maltosyl fluoride was )S-maltose. The results with )3-maltosyl fluoride were interpreted by the assumption of a glycosylation reaction preceding hydrolysis by which a malto-tetraoside is formed by the replacement of fluoride ion by a second substrate molecule or added methyl -maltoside (see Scheme 5). 

Pacsu and Rich" discovered a new method, by which it was possible to obtain the new methyl maltoside heptaacetate in one step and in fairly good yield. The procedure consisted in the treatment of 9-maltose octaacetate in chloroform solution with aluminum chloride at room temperature. Freudenberg and I vers chloro-com pound was not isolated but the reaction mixture was treated with methyl alcohol in the presence of pyridine hexaacetylmaltose methyl 1,2-orthoacetate with m. p. 164 and -1-98.8 was obtained in 30% yield. Pacsu and Rich at-... 

This mixture was then oxidized and homologation of the resulting ketone provided 136. After hydrogenolysis, methyl 5 a-carba-maltoside was isolated [64]. A characteristic of this method is that the rearrangement is done on the disaccharide itself. This method can thus also lead to carba-oligosaccharides through cascade rearrangements [66]. 

Scheme 13. Synthesis of methyl a-C-maltoside 76 via temporary silaketal tethering...

One reason for studying the conformation of the disaccharide maltose is that it contains the same interresidue linkage as found in amylose and amylopectin, the polymers of starch. Therefore, conformations of the maltosyl linkages found in maltotriose or panose would certainly be of interest in the comparison with a calculated energy surface. It would be obvious to include a-maltose, -maltose, and methyl- -maltoside, molecules that differ only at the anomeric center, which is as distant as possible from the disaccharide linkage and therefore unlikely to affect the linkage conformation very much. 

This can be analysed by optical rotation, with some rather interesting results. The sugars that were studied a few years ago were OL -methyl-maltoside, cellobiose and trehalose. They have one factor in common, they are composed of two glucose units, but with different linkages, maltose a-1-4, cellobiose B- 1-4, and trehalose 01-1-1. There are thus different conformations of this molecule, which consists of the same two sugar units. 

In general, the de novo approach applied by the Kishi group for the synthesis of C-oligosaccharides relies on acyclic stereocontrol for the construction of the contiguous chiral centers of at least one of the carbohydrate moieties. The first examples of this approach were reported by this group in 1987 and involved the synthesis of four C-disaccharides, including the C-analogs of methyl maltoside and cellobio-side, from a common synthetic intermediate [70]. 

The two primary hydroxyl groups in maltose and its derivatives show a large difference in reactivity. On selective tritylation, /3-maltose,238 benzyl /3-maltoside,239 and methyl 3-0-(methylsulfonyl)-/3-maltoside127 all gave mainly 6 -0-trityl compounds. Tritylation of cyclohexaamylose130 and amylose132,240 yielded the expected 6-0-trityl derivatives. 

On treatment with 30 equivalents of methanesulfonyl chloride in N,N-dimethylformamide for 8 days at 65°, methyl /3-maltoside gave a mixture of methyl 3,6-dichloro-4-0-(6-chloro-6-deoxy-a-D-glucopyranosyl)-3,6-dideoxy-/3-D-allopyranoside, isolated in 46%... 

Skrydstrup, Beau and co-workers122 have adapted Stork s method to the SmI2-reduction of glycosyl pyridyl sulfones bearing a silicon-tethered unsaturated group at HO-C(2). An example is shown with the synthesis of methyl a-C-zso-maltoside 172 from alkyne 170 via the 5-exo-dig radical cyclization of 171 (Scheme 56).144... 

By way of contrast, when 6.8 equivalents of BzCl was used under identical circumstances, in a manner similar to that observed with methyl (1-maltoside, a hexabenzoate with the 3 -OH free was isolated in 33% yield, and this could be chlorinated in high yield with S 2 inversion by using sulfuryl chloride and pyridine (Scheme 20). 

Richardson and Hough s efforts on the chlorination of sucrose ran in parallel with their studies on the selective chlorination of other readily available disaccharides. One notable piece of work done with Philippe L. Durette involved a study of the regioselective chlorination of methyl (S-maltoside (Scheme 31), which was undertaken with the long-term objective of possibly developing a future synthesis of the natural antitumor agent, amicetin. 

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