Hewitt G. Fletcher

The behavior of some aldoses with 2,2-dimethoxypropane-N,N-dimethylformamide-p-toluenesulfonic acid : I. At room temperature (≈25°)

Abstract When treated at room temperature with a small excess of 2,2-dimethoxypropane in N,N -dimethylformamide solution in the presence of a trace of p -toluenesulfonic acid, 2-acetamido-2-deoxy- D -glucose, 2-acetamido-2-deoxy- D -mannose, 2-acetamido-2-deoxy- D -galactose, and D -glucose yield the corresponding 4,6- O -isopropylidenealdo-pyranoses. D -Mannose, however, gives the known 2,3:5,6-di- O -isopropylidene- D -mannofuranose.

Benzyl 2,3,4-tri-O-benzyl-β-d-glucopyranosiduronic acid and some related compounds

A d-glucuronic acid derivative fully protected with hydrogenolyzable groups except at C-6 has been synthesized. Successive tritylation and benzoylation of benzyl β-d-glucopyranoside gave benzyl 2,3,4-tri-O-benzoyl-6-O-trityl-β-d-glucopyranoside (1). The benzoyl groups in 1 were replaced with benzyl groups to give 2, and the trityl group was then removed by hydrolysis, giving benzyl 2,3,4-tri-O-benzyl-β-d-glucopyranoside (3). Oxidation of 3 with the Pfitzner-Moffatt reagent afforded the corresponding aldehyde (4), which was further oxidized, with iodine and methanolic potassium hydroxide, to the methyl ester 6. Alkaline hydrolysis of 6 gave the desired d-glucuronic acid derivative, benzyl 2,3,4-tri-O-benzyl-β-d-glucopyranosiduronic acid (5). The conversion of 3 into 5 was also achieved, in a one-step process, through the use of chromium trioxide and dilute sulfuric acid in acetone. The ester, 6, was further characterized through the corresponding amide (8), and the steric accessibility of the carboxyl group in 5 was demonstrated through its conversion into the 2-naphthyl ester (7).

The behavior of some aldoses with 2,2-dimethoxypropane-N,N-dimethylformamide-p-toluenesulfonic acid. II. at 80°

Abstract Four aldohexoses were individually subjected to the reagent mixture and temperature cited in the title; in each case, the 2,2-dimethoxypropane was present in only a small molar excess and the p-toluenesulfonic acid was used in trace amounts. D -Mannose (1) afforded the known 2,3:5,6-di-O-isopropylidene- D -mannofuranose (2) in significantly higher yield than when the reaction was conducted at room temperature. The other three aldoses, however, gave products markedly different from those formed under the milder conditions. 2-Acetamido-2-deoxy- D -mannose (3) gave a mixture of products from which methyl 2-acetamido-2-deoxy-2,3-N,O-isopropylidene-5,6-O-isopropylidene-α- D -mannofuranoside (4), 2-acetamido-2-deoxy-2,3-N,O-isopropylidene-5,6-O-isopropylidene- D -mannofuranose (5a), and methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-α- D -mannofuranoside (6a) were isolated. 2-Acetamido-2-deoxy- D -galactose (11) gave compounds identified as methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-β- D -galactofuranoside (12a) and methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β- D -galactopyranoside (13a). 2-Acetamido-2-deoxy- D -glucose (16) afforded methyl 2-acetamido-2-deoxy-5,6-O-isopropylidene-β- D -glucofuranoside (17a) and methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β- D -glucopyranoside (18a). Evidence in support of the structures assigned to these new derivatives is presented.

The chemistry of ribose.

Publisher Summary This chapter discusses the chemistry of ribose and its derivatives, which give ribose on hydrolysis. Yeast nucleic acid is the best source of D -ribose and. The hydrolysis of yeast nucleic acid by sweet almond emulsin gives high yields of guanosine and adenosine and forms a practical basis for the preparation of D -ribose. A tentative identification of ribose may be made through the usual tests for a reducing sugar, specific tests for pentoses and, finally, if the sample is homogeneous and crystalline, through its melting point, specific rotation and optical crystallographic properties. A direct application of paper partition chromatography to a problem of ribose chemistry was made by Barker and Lock who hydrolyzed tetraacetyl-di- D -ribose anhydride and showed by chromatography that only ribose was formed. The acetylation of D -ribose in pyridine solution with acetic anhydride at various temperatures is studied.

The inhibitory activity of 2-acetamido-2-deoxy-D-gluconolactones and their isopropylidene derivatives on 2-acetamido-2-deoxy-β-D-glucosidase

Abstract 2-Acetamido-2-deoxy- D -glucono-1,4-lactone ( 1 ) and 2-acetamido-2-deoxy- D -gluconic acid ( 3 ) have been examined for inhibitory activity against 2-acetamido-2-deoxy-β- D -glucosidase from bull epididymis. Crystalline 1 and 3 were compared with the known, crystalline 2-acetamido-2-deoxy- D -glucono-1,5-lactone ( 2 ), and a correlation of the activities of these compounds with various factors is presented. The inhibition constant of the 1,5-lactone 2 is lower (0.45μ M ) than that (4.43μ M ) of the 1,4-lactone 1 . The effect of time is the opposite; whereas the activity of solutions of 2 decreases with time, solutions of 1 show an increase in inhibitory power, but both reach an equilibrium after 5 h. The free acid 3 exhibits no inhibitory activity. 2-Acetamido-2-deoxy-5,6- O -isopropylidene- D -glucono- 1,4-lactone ( 4 ) and 2-acetamido-2-deoxy-4,6- O -isopropylidene- D -glucono-1,5-lactone ( 5 ), which are appropriately protected to prevent conversion into the other lactone isomer, were also tested; 4 has 1/1000th the activity of 5 .

2-Deoxy-d-ribose. I. A simplified preparation of 2-deoxy-d-ribose based on treatment of α-d-glucose monohydrate with solid calcium hydroxide

Abstract Heating α- d -glucose hydrate with an excess of solid calcium hydroxide under nitrogen at 115–120 ° for 1 hr. affords a mixture which, after removal of excess alkali, may be submitted to the Ruff degradation to give 2-deoxy- d -ribose as its anilide in a high state of purity in 8–9% yield. With these inexpensive materials and this simple procedure, relatively large quantities of 2-deoxy- d -ribose may easily be prepared using ordinary laboratory equipment.

Applications in the Carbohydrate Field of Reductive Desulfurization by Raney Nickel

Publisher Summary This chapter discusses various applications in the carbohydrate field of reductive desulfurization by Raney nickel. Reductive desulfurization with Raney nickel is a reaction that requires but the simplest of techniques, is carried out under rather mild conditions, and affords relatively good yields; it is a standard and well-recognized reaction, having found use in practically all the various fields of organic chemistry. The chapter discusses Raney nickels applications in sugar fields. Desulfurization carried out in aqueous alcohol has been observed to give rise to acetaldehyde; in view of the well-known dehydrogenating action of Raney nickel it seems likely that the solvent may play a part as a hydrogen donor in the reaction. In practice the sulfur-containing derivative is dissolved or suspended in a suitable solvent, treated with a sufficient quantity of Raney nickel, and either left at room temperature or heated under reflux, recovery of the product being effected by concentration of the liquid phase. The utility of Raney nickel desulfurization in solving problems of configuration in the sugar series is demonstrated in the ω-desoxyglycitol series. Reductive desulfurization with Raney nickel of the mercaptolysis products of streptomycin has supplied one of the keys to the elucidation of the structure and configuration of that antibiotic.

Syntheses of 2-acetamido-2-deoxy-D-glucono-1,4-lactone and some isopropylidene acetals of 2-acetamido-2-deoxy-D gluconic acid derivatives

Abstract Brief treatment of 2-acetamido-2-deoxy- D -gluconic acid ( 3 ) with boiling acetic acid affords, after purification, 2-acetamido-2-deoxy- D -glucono-1,4-lactone ( 1 ). The same lactone may also be prepared through hydrolytic cleavage of the isopropylidene group in 2-acetamido-2-deoxy-5,6- O -isopropylidene- D -glucono-1,4-lactone ( 4 ). When the mixture of compounds obtained by the oxidation of 2-acetamido-2-deoxy- D -glucose was treated with an isopropylidenating agent, the crystalline lactone 4 was among the products isolated. In addition, in the course of that reaction, isopropylidene acetals of 2-acetamido-2-deoxy- D -gluconic acid esters, 6 – 8 and 9 , were formed. When 4 was treated with p -toluenesulfonyl chloride in pyridine, β-elimination occurred to yield 2-acetamido-2,3-dideoxy-5,6- O -isopropylidene- D - erythro -hex-2-enono-1,4-lactone ( 10 ). With methanol, 4 gave methyl 2-acetamido-2-deoxy-5,6- O -isopropylidene- D -gluconate ( 7 ), which spontaneously reverted to 4 . The susceptibility of lactone derivatives to the action of alcohols is briefly discussed.

De-O-benzylation of benzyl ethers of carbohydrate derivatives by thiols in the presence of boron trifluoride.

Abstract Based on experiments with 2,3,4,6-tetra- O -benzyl-α- D -glucopyranose ( 1 ), 1,3,4,6-tetra- O -benzyl- D -mannitol ( 9 ), and ethyl 3,5,6-tri- O -benzyl- D -glucofuranoside ( 7 ), a mixture of boron trifluoride etherate and ethanethiol or 1,2-ethanedithiol constitutes a practical reagent for the removal of O -benzyl groups from benzyl ethers of carbohydrates at room temperature. When 1,2-ethanedithiol was used, 1 and 7 afforded D -glucose ethylene dithioacetal [ 2 ; 2-( D - gluco -pentahydroxypentyl)-1,3-dithiolane], the benzyl groups appearing as benzyl sulfide ( 3 ) and tribenzylsulfonium tetrafluoroborate ( 4 ). With ethanethiol and boron trifluoride, 1 gave a mixture of the anomeric ethyl 1-thio- D -glucopyranosides ( 5 ) and dibenzylethylsulfonium tetrafluoroborate ( 6 ). The nonreducing compound 9 simply gave D -mannitol ( 10 ) under these conditions. A mechanism for this new debenzylation procedure is proposed.

The inhibitory activities of 2-acetamido-2,3-dideoxy-D-hex-2-enonolactones on 2-acetamido-2-deoxy-β-D-glucosidase

Treatment of 2-acetamido-2-deoxy-D-mannono-1,4-lactone with dicyclohexylamine in ethanolic solution afforded an unsaturated 1,4-lactone, 2-acetamido-2,3-dideoxy-D-erythro-hex-2-enono-1,4-lactone (1), in good yield. 2-Acetamido-2,3-dideoxy-D-threo-hex-2-enono-1,4-lactone (2) was similarly prepared from 2-acetamido-2-deoxy-D-galactono-1,4-lactone. An unsaturated 1,5-lactone, 2-acetamido-2,3-dideoxy-D-threo-hex-2-enono-1,5-lactone (4), was obtained through the oxidation of 2-acetamido-2-doexy-4,6-0-isopropylidene-D-galactopyranose with silver carbonate on Celite, followed by mild hydrolysis. The inhibitory activity of four isomeric 2-acetamido-2,3-dideoxy-D-hex-2-enonolactones [1, 2, 4, and 2-acetamido-2,3-dideoxy-D-erythro-hex-2-enono-1,5-lactone (3)] was assayed against 2-acetamido-2-deoxy-beta-D-glucosidase from bull epididymis. Only the erythro lactones 1 and 3 are weak competitive inhibitors, whereas the threo lactones 2 and 4 are practically inactive. The 1,4-lactone 1 inhibited 2-acetamido-2-deoxy-beta-D-glucosidase more strongly than the 1,5-lactone 3. The lactones 1-4 were found to be quite stable in aqueous solution or under inhibitory-assay conditions. In addition, two 2-acetamido-2-deoxy-D-glycals, 2-acetamido-1,5-anhydrohex-1-enitol (7) were tested; both are 10 times as active as 1.