Lactose octaacetate

To achieve these lactose-purpurinimide conjugates 89-93, in the macrocycle positions 3, 8, 12, the purpurin-18-methyl ester 81 had to undergo several chemical transformations to obtain the desired hydroxymethyl group.68 Such alcohol derivatives were reacted with lactose octaacetate in the presence of boron trifluoride diethyl etherate to induce the acetylated lactose-purpurinimide derivative which, after deacetylation reaction conditions, yielded the desired compounds in excellent amounts (Scheme 12). 

Parrish, F. W., Ross, K. D. and Simpson, T. D. 1979B. Formation of /3-lactose from a-and /3-lactose octaacetates, and from a-lactose monohydrate. Carbohydr. Res. 71, 322-326. 

The 8-methoxycarbonyloctyl derivative of lactose has been prepared from lactose octaacetate in the presence of tin(lV) chloride or from acetobromolactose in the presence of silver triflate [123,124] and converted into the derivative (108) with a free 4 -hydroxyl group [125] via the 4, 6 -0-benzylidene derivative. The benzyl lactoside (109) was converted into the benzyl ether (110) by the action of benzyl bromide and tetrabutylammonium bromide on the dibutylstannylene derivative [126] and this was converted into the benzoate (111). Phase transfer benzylation of the benzyl lactoside (112) has given the lactose derivative (113) with a free 3-hydroxyl group in 38% yield [118]. 1,6-Anhydrolactose has also been used for the preparation of the protected lactose derivative (114) [127]. 

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 ... 

Lactose octaacetate Fio. 2.—HaskinB, Hann, and Hudson s Synthesis of Lactose. (Con. from p. 186)... 

Chromatography of mixed a, -lactose octaacetates on columns of silica or calcium carbonate is priiferable to that on alumina, which causes preferential hydrolysis of the acetyl group on the oxygen atom at C-1. 

In the reaction of lactose octaacetate (258) with phosphorus pentachloride and aluminum trichloride, Hudson and Kun found, in addition to the anticipated hepta-O-acetyl-lactosyl chloride, a new disaccharide derivative having the structure of the heptaacetate of 4-O-jS-D-galactopyranosyl-a-D-altropyranosyl chloride (259). The yield of 259 was raised to 35-40% when 50 grams of octa-O-acetyl-lactose (258) was heated for 20 minutes with 100 grams of aluminum... 

We present herein an efficient synthesis of hepta-O-acetyl-P-lactosyl azide 3 via phase transfer catalysis under conditions developed by our group (Scheme 31.1). Firstly, P-lactose octaacetate was transformed into acetobromo-a-lactose 2, using a commercially available solution of 33% HBr in AcOH. Without further purification, bromide 2 was converted under mildly basic, phase transfer catalyzed conditions into compound 3 ° in 88 to 93% yields in two steps. Other methods for the synthesis of glycosyl azides require strong Lewis acid-catalyzed treatment with TMSN3 for several hours" or the use of sonication. These methods can be lengthy and expensive, and often provide anomeric mixtures of azides. 

A 33% solution of HBr in AcOH (2.28 mL, 13.0 mmol, 13.0 equiv.) was added in one portion to a solution of lactose octaacetate (679 mg, 1.0 mmol, 1.0 equiv.) in dry CH2CI2 (3.0 mL, 0.33 M). The resulting mixture was stirred at room temperature for 1 hour. Upon completion of the reaction (TLC 3 2 EtOAc-Hexanes), the mixture was poured slowly into a cold, saturated aqueous solution of NaHC03 (50 mL), the flask was washed with CH2CI2 (3 x 10 mL) and the contents were added to the mixture. 

A remarkable inertness towards acylation is shown by the secondary hydroxyl group on C-3 in maltose, lactose, and their methyl j8-glycosides. Benzoylation of maltose with 10 molar equivalents of the acid chloride in pyridine gave122 the octabenzoate and the l,2,6,2, 3, 4, 6 -hepta-0-benzoyl derivative in the ratio of 5 6, and treatment of /3-maltose monohydrate with 8.8 molar equivalents of acetyl chloride in pyridine-toluene at 0° gave123 the 1,2,6,2, 3, 4, 6 -heptaacetate and the octaacetate in the ratio of 27 10. Under similar conditions of benzoylation, cellobiose was converted into its oc-... 

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... 

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. 

Hepta-O-acetyl-a-lactosyl bromide and iodide are conveniently prepared by treating octa-0-acetyl-/3-lactose with hydrogen bromide and hydrogen iodide, respectively, in glacial acetic acid. The fluoride, prepared by treating the octaacetate with hydrogen fluoride, was found to be appreciably less susceptible to dehalogenation than the other halides saponification with sodium methoxide in methanol produces a-lactosyl fluoride. 

The deacylation of the octaacetates of cellobiose, lactose, maltose and melibiose with Aspergillus niger lipase leads to the formation of the respective carbohydrate heptaacetates with a free anomeric OH-group at Cl in high yield1230, 232]. With... 

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