Methyl 3-lactoside

In entirely analogous fashion, the selective esterification of various other common disaccharides by other acylating agents was investigated. One notable example is the selective benzoylation of methyl (3-lactoside with benzoyl chloride, which again produced many interesting results that are recorded in a series of papers with Ram... 

SCHEME 19. One representative example of Hough, Richardson, and Bhatt s selective benzoylation of methyl p-lactoside (1975). 

Hough, and Richardson s regioselective chlorination of the 3 -OH of methyl p-lactoside following regioselective... 

R. S. Bhatt, L. Hough, and A. C. Richardson, Selective chlorination of methyl p-lactoside with mesyl chloride in DMF, Carbohydr. Res., 49 (1976) 103-118. 

Small-intestine lactase (GH 1), the absence of which is associated with lactose intolerance in a large proportion of the adult population, was probed with monodeoxy as well as selected mono-O-methyl derivatives in the galactose moiety of methyl lactosides.112 This enzyme required hydroxyl groups at C-2 and also C-3, while neither the presence of a 4-OH group nor a specific configuration at C-4 was prerequisites for successful hydrolysis. A 6 -deoxy lactoside was readily hydrolyzed, but the absence of 6-OH in the gluco moiety caused it to be a poor substrate. 

K. Bock and K. Adelhorst, Derivatives of methyl p-lactoside as substrates for and inhibitors of p-D-galactosidase fromil. coli, Carbohydr. Res., 202 (1990) 131-149. 

Compound (44 g, NHAc form) (Scheme 14) was found to be a competitive inhibitor for CBHI cellulase (family 7) from Trichoderma reesei, when 4-methyl-umbelliferyl / -lactoside was used as substrate. Therefore (44 g, NHj form) was coupled to CH-Sepharose 4B, and the affinity gel was very effective for the purification of cellobiohydrolases from a crude commercial cellulolytic extract of T. reesei [40c]. Using the same approach aryl 1,4-dithioxylobioside and l,4,4 -trithioxylotrioside (44 h, NH2 form) were coupled to CH-Sepharose 4B to give affinity gels which were used for the purification of xylanases [40a,b]. 

To further exploit the potential usefiilness of this new family of clusters, monoadduct 54 was saponified into 55 (0.05 M NaOH, quant) and condensed to L-lysine methyl ester using 2-ethoxy-l-ethoxycarbonyl-l,2-dihydroquinoline (EEDQ) to give extended dimer 56 in 50 % yield together with monoadduct in 15 % yield [75]. Additionally, tert-butyl thioethers 52 could be transformed into thiols by a two step process involving 2-nitrobenzenesulfenyl chloride (2-N02-PhSCl, HOAc, r.t, 3h, 84%) followed by disulfide reduction with 2-mercaptoethanol (60%). Curiously, attempts to directly obtain these thiolated telomers by reaction with thioacetic acid f ed. These telomers were slightly better ligands then lactose in inhibition of binding of peanut lectin to a polymeric lactoside [76]. 

A suspension of methyl p-lactoside 13 (S.O g, 14 mmol) in benzene (130 mL) was refluxed for 17 h in the presence of BujSnO (4.18 g, 16.6 mmol) in a flask equipped with a Dean-Static separator. Then allyl bromide (20 mL) and tetrabutylammonium bromide (2 g, 6.2 mmol) were added, the solution was refluxed for 3 h, and the volatiles were evaporated. The residue was dissolved in water and washed twice with ethyl acetate. The aqueous phase was evaporated to dryness, benzene (ISO mL) and BujSnO (3.83 g) were added to the residue and the mixture was refluxed as before for 17 h. Then allyl bromide (IS mL) and tetrabutylammonium bromide (1.5 g) were added, and the solution was again refluxed for SO min. The volatiles were evaporated, and the residue was taken over in methanol. The crystalline precipitate of BrBi SnOSnBu OH), mp 80-81°C, was removed by filtration and the mother liquor was evaporated. Addition of ethyl acetate to the residue gave the allyl ether 14 as a crystalline compound (3.88 g, 70%) mp 107-112°C [a]D + 20° (c 1.0 in water). 

The benzylidene derivative (94) has been converted into the alcohol (95) [97, 98] using the diborane — trimethylamine — aluminium chloride reagent [99] and into the diol (96) [95, 100, 101]. Veyrieres has converted methyl P-lactoside (and the corresponding allyl lactoside) into the 3-O-allyl ether (97) in good yield [102] by alkylation of the dibutylstannylene derivative in the presence of tetrabutylammonium iodide [103, 104], and this was converted into the alcohol (98) and the triol (99) [105]. Veyrieres [106] has also converted (97) into the per-p-bromobenzyl derivative and deallyl-ated the product to give a derivative with a free 3 -hydroxyl group. The diol (100) [107] has been converted by the stannylation procedure [108, 109] into the alcohol (101) [110, 111]. The partially acetylated benzyl P-lactoside (103) [101,112, 113] has been converted into the alcohol (104) via the orthoacetate [113]. 

The perbenzoyl derivative (105) [114,115] has been prepared via the 4, 6 -0-iso-propylidene derivative of lactose and the methyl lactoside (106) via the 4, 6 -Oben-zylidene derivative [116]. Benzoylation of lactose has given a perbenzoyl derivative with a free 3-hydroxyl group [117, 118]. 

The methyl 3 -0-allyl-P-lactoside (97) prepared by Veyrieres by the allylation of the dibutylstannylene derivative in the presence of tetrabutylammonium bromide [102] was converted into the per-p-bromobenzyl ether and deallylated to give (306). This was condensed "[106] with the chloride (282) in the presence of silver triflate to give a tetrasaccharide in 68 % yield. This was far superior to the condensation of the oxazoline (294) with (306) which gave a very low yield (9%) of tetrasaccharide. Depro-... 

In order to try to overcome some of the problems associated with chemical synthesis of oligosaccharides containing N-acetylneuraminic acid, Sabesan and Paulson [277] have used a combination of chemical and enzymatic methods using purified sialyl-transferases in the presence of CMP-iV-acetylneuraminic acid and synthetic acceptor molecules to give sialyl derivatives of oligosaccharides which were characterised by NMR. Thus, methyl P-D-galactopyranoside, methyl P-D-lactoside and iV-acetyl-... 

The fact that methyl 2,3- and 2,6-di-O-benzyl galactopyranosides give the same 2,3,6-trisubstituted compound has been utilized in the synthesis of the trisaccharide moiety of gangliotriosyl-ceramide. The intermediate methyl lactoside having only the axial OH-4 of the galactose unit free resulted from a mixture of both penta-O-benzyl lactosides, thus avoiding the separation of the 4,6- and 3,4-O-isopropyIidene precursors [164],... 

A nuclear magnetic relaxation study85 of lactose (17), which is a basic constituent disaccharide unit of all gangliosides, demonstrates that this molecule reorients anisotropically. The favored axis of molecular reorientation appears to lie along the axis of the molecule and therefore is reflected in the shorter T, value at C-4 of the galactose residue. The apparent differences between the relaxation times observed for the C-l resonances of the a (17a) and /3 (17b) isomers may also be reflected in their differing C—H orientations relative to the anisotropic axis. Similar anisotropic motion was observed for methyl /3-lactoside,85 methyl /3-cellobioside,84 and other disaccharide derivatives in solution. 

Other interesting examples of segmental motion that clearly reflect the sequence of monosaccharide units in a given oligosaccharide are the disaccharide benzyl /8-lactoside and the trisaccharide benzyl 6-0-(j3-lactosyl)-/3-D-glucopyranoside, which are attached via complexation to heptakis(2,6-di-0-methyl )cyclomalto-... 

Fig. (9). Inhibition of anti-lactose antibodies by increasing amounts of methyl P-lactoside and lactose (A) and by the agar diffusion method (B).

Figure III-16 Acid-catalyzed hydrolysis of acetal linkages in a-methyl-D-lactoside.

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