Galactopyranoside, methyl oxidation

Scheme II.—Utilization of a 2-Nitrobenzylidene Protecting Group in the Synthesis of Methyl 6-Deoxy-2,3-di-0-/3-D-galactopyranosyl-a-L-galactopyranoside. /3-o-GaIacto-pyranosyl (R ) Substituents Were Introduced by Koenigs-Knorr Syntheses, and the Photochemical Cleavage, at 350 nm, of the 2-Nitrobenzylidene Groups Proceeded Regiospecifi-cally. Yielding, Following Oxidation, a 95% Yield of the 3-Hydroxy-4-(2-nitrobenzoate) Derivative.

The ease with which the hexosyl-4-ulose derivative 109 undergoes dehydration was demonstrated in a non-enzymic, model reaction. Oxidation of methyl /8-D-galactopyranoside with oxygen and a platinum catalyst, followed by hydrogenation over the same catalyst, resulted in a 35% yield of methyl /8-D-fucopyranoside,423 presumably formed through reactions analogous to those in Fig. 3. 

It is well established that oxygen in the presence of platinum (Adams catalyst) can achieve specific oxidation of secondary alcohols by a preferential attack upon hydrogen in an equatorial position (25). Catalytic oxidation of methyl a- and /3-D-galactopyranoside (26), fallowed by catalytic reduction with hydrogen, led to the formation of methyl a- and /3-6-deoxy-D-galactopyranoside (D-fuco-pyranoside) in 15% and 35% yield, respectively. This oxidation-reduction sequence with selective oxidation at carbon 4 as the initial step is structurally closely related to the above described pathway for TDPG-oxidoreductase. 

Cognate preparation. Methyl 2,3,4,6-tetra-O-acetyl-fi-D-galactopyranoside. Use 13.5 g (0.033 mol) of 2,3,4,6-tetra-O-acetyl-a-D-galactopyranosyl bromide (Expt 5.109), 19 g of anhydrous calcium sulphate, 5.6 g of yellow mer-cury(n) oxide, 0.5 g of mercury(n) bromide, 90 ml of dry chloroform and 90 ml of dry methanol under the reaction conditions and subsequent isolation procedure described above 7.5 g (63%) of methyl 2,3,4,6-tetra-0-acetyl-/ -D-galactopyranoside, m.p. 96-97 °C, [oc]d° —28.0° (c2.5 in CHC13), is obtained after several recrystallisations from ethanol. 

Under the same conditions, the reactivity of hydroxyl groups is OH-2 > OH-3 for methyl 4,6-O-benzylidene-a-D-glucopyranoside, and OH-3 > OH-2 for the P-ano-mer [48] or for the corresponding galactopyranoside [49]. The hydroxyl group in position 2 is the most reactive in sucrose benzylation [27]. It seems that the cis-OR substituent activates the adjacent equatorial hydroxyl group [33] in benzylations in the presence of barium oxide. 

Attempted sodium hydride mediated benzylation of methyl 3-0-benzoyl-4,6-0-benzylidene-P-D-galactopyranoside failed due to a benzoyl migration [65]. The acyl group migration and removal are also responsible for only 62 % yield of benzyl 2-acetamido-3,6-di-0-acetyl-4-0-benzyl-2-deoxy-a-D-glucopyranoside. Thallium eth-oxide instead of sodium hydride or alkoxide successfully restrained the acetyl group migration in this reaction [35]. 

In these catalyzed oxidations, formic acid production did not parallel the uptake of lead tetraacetate49 and, particularly with the D-mannopyrano-side and D-galactopyranoside, fell far short of the theoretical value of one mole per mole (see Fig. 2). Methyl a-D-mannoside yielded only one third of a mole of free acid per mole, a result which agreed well with the earlier formulation97 of the ester (XLVII) as the reaction product to be expected. The almost equally low yield of formic acid from methyl a-D-galactopyrano-... 

The synthesis of this substance was also effected by F. Smith.2 Methyl 6-trityl-a-D-galactopyranoside, in acetone solution, was treated six times with dimethyl sulphate and sodium hydroxide solution. The imperfectly methylated material thus obtained was then subjected to two treatments with methyl iodide and silver oxide. The necessity for so many treatments with methylating reagents emphasizes the difficulty of etherifying a glycoside substituted by the trityl radical in position 6. Subsequent to removal of the trityl radical, the methyl 2,3,4-trimethyl-(33) J. S. D. Bacon, D. J. Bell and J. Lorber, J. Chem. Soc., 1147 (1940). 

Some examples are known where the formation of alternative, anhydro-ring structures is possible, and the deformation of the molecule required in the alternative reactions is approximately the same, so that entropy changes may be largely neglected. In such cases the ethylene oxide ring is not favored. The action of bases on methyl 3,4-di-0-acetyl-2,6-di-0-tosyl-/J-D-glucopyranoside and on methyl 2,6-di-0-mesyl- -D-galactopyranoside affords predominantly the 3,6-anhydro-2-0-sulfonyl derivative in each case. 

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