3-Neolactose

A further study147 of the conditions required for the rearrangement showed that aluminum chloride in the absence of phosphorus penta-chloride would chlorinate the lactose octaacetate and give good yields of the heptaacetylneolactosyl chloride. Apparently the reaction involved an adsorption of lactose octaacetate at the surface of the insoluble aluminum chloride since the acetate was largely removed from the chloroform solution by the solid aluminum chloride and finely divided aluminum chloride was more reactive than coarse lumps. Heptaacetyllactosyl chloride was probably formed first and then transformed into the isomeric neolactose compound since normal yields were obtained when the heptaacetyllactosyl chloride was substituted for the octaacetate. Richtmyer and Hudson148 were able to obtain yields up to 45% from lactose octaacetate by using a mixture of aluminum chloride and phosphorus penta-chloride. The over-all isomerization may be illustrated as follows ... 

The structure of ueolactose was established in a second paper by Kunz and Hudson." By deacetylation of the a-octaacetate they obtained neolactose as a sirup, with [a]o about +35 in water. Its phenylosazone differed from that of lactose, hence the new sugar could be neither lactose (4-galactosidoglucose) nor Bergmann s 4-galactosido-mannose which might have been formed by simple epimerization at... 

It had been found that the equimolecular mixture of n-galactose and D-altrose resulting from the acid hydrolysis of neolactose had a negative rotation, calculated as hexose, of [ ]d —8.95° in water. Knowing the equilibrium rotation of n-galactose to be +80°, Kunz and Hudson" estimated that n-altrose would have [ajn —98° in water. 

In a new study of neolactose, Richtmyer and Hudson improved the method of preparing acetochloroneolactose a 35-40% yield of the recrystallized material was obtained consistently by heating each 50 g. of octaacetyllactose in 350 ml. of absolute chloroform with 100 g. of powdered technical aluminum chloride and 50 g. of powdered phosphorus pentachloride for twenty minutes in a bath at 55-58°. By removing the chlorine atom with silver carbonate and aqueous acetone, and deacetylat-ing the heptaacetates thus formed (see Table II), they isolated the parent disaccharide. Crystalline neolactose had a rotation [a]D +34.6—> +35.5°, which is in agreement with the equilibrium value +35° reported by Kunz and Hudson" for sirupy neolactose. 

Experimental evidence for the presence of the /9-linkage in neolactose and celtrobiose is based upon the enzymic hydrolysis of these sugars. Helferich and Pigman r orted that the /9-D-galactosidase component of sweet almond emulsin cleaves neolaetose (4-j8-D-galactosido-D-altrose),... 

Pigman has prepared crystalline u-altrose from neolactose by cleavage of the disaccharide with sweet almond emulsin, followed by removal of the D-galactose by fermentation with yeast. This procedure avoids the transformation of any n-altrose to u-altrosan, the non-reducing anhydride which is formed to the extent of 57% in the hydrolysis of neolactose by acids. 

Concerning the mechanism of the rearrangement of sugar acetates by aluminum chloride, there is very little to be added at the present time. The reaction proceeds equally as well with the a-octaacetate of cellobiose as it does with the /3-octaacetate of lactose.Under the most favorable conditions so far discovered, it appears that octaacetyl-lactose is converted to about equal amounts of acetochlorolactose and acetochloroneolactose similar results were obtained with octaacetyl-cellobiose. Although Kunz and Hudson believed acetochlorolactose to be the primary reaction product, which was transformed subsequently to the isomeric neolactose derivative, later experiments by Richtmyer and Hudson did not substantiate this view. In an uncompleted study of the action of a mixture of aluminum and phosphorus chlorides upon pentaacetyl-D-glucose, Richtmyer and Hudson have demon.strated that both D-altrose and n-mannose derivatives are formed by rearrangement of the D-glucose molecule. 

In the synthesis of n-altrose from D-ribose, first effected by Levene and Jacobs, the only crystalline intermediate was the characteristic calcium D-altronate -3.5 H2O. The sirupy lactone prepared from it was then reduced to n-altrose with sodium amalgam, as mentioned earlier in this review. Calcium n-altronate has been obtained from other sources also, such as the aluminum chloride rearrangement of the acetates of lactose, cellobiose and glucose and subsequent transformation of the neolactose, celtrobiose and altrose derivatives thus produced (see Section... 

The acetylated neolactose methyl 1,2-orthoacetate was isolated in crystalline form when the original methanol solution was evaporated in air to a sirup and triturated with ethanol. After several recrystallizations the compound (XIV) had m. p. 121-122 and [a]n -t-25.3 . It showed the reactions and properties which characterize the sugar methyl orthoacetates, including stability of the orthoacetate group toward alkaline hydrolysis. When the new compound was treated with an anhydrous 0.1 V solution of hydrogen chloride in chloroform, it was converted into the crystalline heptaacetyl-a-neolactosyl chloride. Alkaline hydrolysis also indicated the presence of six acetyl groups, whereas dilute acid removed seven. 

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