THE SYNTHESIS OF 4-O-β-D-GALACTOSYL-D-GLUCOSE (LACTOSE)

Abstract

4-0-8-D-Galactosyl-D-glucose (lactose) has been synthesized using a modification of the Koenigs-Icnorr reaction. INTRODUCTION4-O-~-~-Galactosyl-D-glucose (lactose) occurs in all mammalian milk to the extent of about 5Yv. I t has also been reported in the long-styled pollen of forsythia flowers. I t was prepared in 1942 by Haskins, Hann, and Hudson (1) from epilactose (4-0-0-Dgalactosyl-D-mannose), but has not previously been synthesized directly.One of the most useful methods of disaccharide synthesis is that due to Koenigs and Knorr (2). They prepared tetra-0-acetyl-a-D-glucopyranosyl-bromide and found that this, in the presence of silver carbonate or dry pyridine, reacted with methanol to form methyl-0-D-glucopyranoside. The reaction-essentially the elimination of hydrogen halide between a glycosyl halide and a hydroxyl group-was adapted for disaccharide synthesis by Helferich (3) and by Hudson (4). They allowed the acetobrom sugar to react with a suitably substituted sugar derivative in a dry inert medium in the presence of silver carbonate or silver oxide. With modern refinements-use of "Drierite" as drying agent and small amounts of iodine as catalyst-good yields can be obtained in the case of 1 -+ 6 linked hexose disaccharides, where a primary hydroxyl group is involved. However, up to the present only small yields have been obtained in the case of disaccharides where a secondary hydroxyl group is involved. This is due to the lesser reactivity of the secondary hydroxyl group and to steric hindrance by the alcohol component due to the presence of the hemiacetal ring and the substituent groups. I t was thought that this second factor might be lessened-and thus greater yields obtained-by the use of an open-chain sugar derivative as the alcohol reactant. Here the accessibility of the hydroxyl group is much greater than in the corresponding ring compound.In the present work 2,3-5,6-di-0-isopropylidene-D-glucose diethyl acetal was condensed with acetobrom-D-galactose under standard Koenigs-Knorr conditions (5). The reaction mixture was boiled with sodium hydroxide solution to remove acetyl groups from the product and to destroy excess acetobrom-galactose, cooled, and deionized. Hydrolysis of isopropylidene and acetal groups was carried out with hot dilute acetic acid. The resulting mixture of mono-and di-saccharides was separated by charcoal-and paperchromatography. Lactose was obtained crystalline in 3.57, yield, which is well in excess of the yields usually obtained from Koenigs-Knorr syntheses where a secondary hydroxyl group is involved. Two other disaccharide fractions were obtained in small yield. These have not been completely identified but presumably result from isomers of 2,3-5,6-di-0-isopropylidene-D-glucose diethyl acetal. These are inevitably present in small amount as a result of the method of preparation of this compound (via a mercaptal mixture (8) consisting mainly of the 2,3-5,6-di-0-isopropylidene derivative). EXPERIMENTALOptical rotations were measured in water a t 2 1°f 2' C. The fo...

SYNTHESIS OF 4-O-β-D-GALACTOPYRANOSYL-D-GALACTOSE

“…We now report the synthesis of both I1 and I. Previous work (4) had shown that acetobromo sugars will readily form glycosides with acyclic sugar derivatives which possess a free hydroxyl group. In the present study aldehydo-D-galactose diethyl dithioacetal (5) was condensed with acetone to yield a mixture containing the 2,3;4,5-(IIIa, R = SEt) and 2,3;5,6-di-0-isopropylidene (IIIb, R = SEt) derivatives (cf.…”

Structure elucidation of sesquiterpene dilactones from Mikania scandens

“…6.00 (d, 3) 2.85 (dd, 1.8 (m) 7.70 (t, 5.42 (br) 4.7 (m) 6.18 (d, 3) 1.10 3.45 (m)» 12, 2.5) 1) 5.99 (d, 3) 17 4.84 (d, 6.23 (d, 7.24 (d, 3.5 (dd, 4.98 (dd, 4.18 (td, 1.9 (c) 5.98 " Spectra were run in DMSO-de solution on a Varían -0 nmr spectrometer using tetramethylsilane as internal standard.® Superimposed signals were frequently separated in pyridine-ds solution; such spectra are given in the Experimental Section. Chemical shifts are quoted in parts per million, signals being denoted in the usual way: d, doublet; dbr, broadened doublet; t, triplet; q, quartet; nm, narrow multiplet; c, complex signal whose center is given.…”

“…Limits of error 0.1 Hz. 6 Difficult to determine owing to proximity irradiation frequency to signal observed. 0 Broadening due to allylic coupling to He-(/ < 0.5 Hz).…”

Ganglioside series. IV. Preparation of 2,3-di-O-acetyl-1, 6-anhydro-.beta.-D-glucopyranose and its utilization in the synthesis of oligosaccharides

“…Because of these features of the glucose molecule, the synthesis of disaccharides of the lactose type has posed a problem ever since. Curtis and Jones,6 using the open chain form of glucose, condensed 2,3,5,6di-O-isopropylidene-D-glucose diethyl acetal with acetobromogalactose and obtained a mixture of mono-and disaccharides from which lactose could be separated by charcoal and paper chromatography.…”