Emmanuel Zissis

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).

Binding studies on a mouse-myeloma immunoglobulin a having specificity for β-D-(1→6)-linked D-galactopyranosyl residues

Abstract The free energies of binding between immunoglobulin A J 539 (Fab′) and methyl 6- O -acetyl-β- D -galactopyranoside ( 1 ) and 6- O -β- D -galactopyranosyl-1,2:3,4-di- O -isopropylidene-α- D -galactopyranose ( 2 ) have been measured. The values found suggest that bulky substitution on O′-6 or O-1, O-2, O-3, and O-4 in the hapten 6- O -β- D -galactopyranosyl- D -galactose ( 3 ) does not interfere with effective binding of that ligand and the immunoglobulin. This conclusion supports the postulations that ( a ) the ligand 3 binds only on one side of the molecule, and ( b ) the combining site of the immunoglobulin J 539 appears to be located on an exposed surface area.

D-glucose diphenyl dithioacetal, phenyl 1-thio-α-D-glucopyranoside, phenyl 1-thio-α-D-glucofuranoside, and some related compounds

Abstract D -Glucose diphenyl dithioacetal has been prepared for the first time, in a 71% yield, by the action of benzenethiol and concentrated hydrochloric acid on D -glucose. It has been converted by acid into phenyl 1-thio-α- D -glucopyranoside and by mercuric chloride—mercuric oxide into phenyl 1-thio-α- D -glucofuranoside; the ring structures of these thioglucosides were established by reductive desulfurization. The thioglucoside acetates, upon oxidation with hydrogen peroxide in glacial acetic acid, yielded the corresponding α- D -glucopyranosyl and α- D -glucofuranosyl phenyl sulfones. An α- D -glucofuranosyl phenyl sulfoxide could be obtained only in very small yield. Some infrared data on these compounds are included.

Synthesis of 6-O-(6-O-β-d-galactopyranosyl-β-d-galactopyranosyl)-d-galactopyranose by use of 2,3,4-tri-O-acetyl-6-O-(chloroacetyl)-α-d-galactopyranosyl bromide, a key intermediate for the solid-phase synthesis of β-(1→6)-linked d-galactopyranans

Abstract 2,3,4-Tri- O -acetyl-6- O -(chloroacetyl)-α- d -galactopyranosyl bromide ( 5 ) has been prepared. When condensed with 1,2,3,4-tetra- O -acetyl- d -galactopyranose, it yielded 1,2,3,4-tetra- O -acetyl-6- O -[2,3,4-tri- O -acetyl-6- O -(chloroacetyl)-β- d -galactosyl]- d -galactopyranose ( 6 ). The O -chloroacetyl group could be selectively removed from 6 by treatment with thiourea, and the resulting product was again condensed with 5 , to yield, after deprotection, the trisaccharide title-compound.

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 .

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.

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.

The preparation and properties of some 2-acetamido-2-deoxyhexonic acids

Abstract The oxidation of 2-acetamido-2-deoxy- D -mannose (Scheme I, 1 ) with aqueous bromine in the presence of barium benzoate leads to the isolation of crystalline 2-acetamido-2-deoxy- D -mannonic acid ( 2 ). With aqueous dicyclohexylamine, 2 gives dicyclohexylammonium 2-acetamido-2-deoxy- D -mannonate ( 4 ), a crystalline salt readily distinguishable from its known D - gluco isomer ( 5 ). Both 2 and 4 are convertible into the known 2-acetamido-2-deoxy- D -mannono-1,4-lactone ( 3 ), showing that the configurations assigned to these structures are correct. As the salt ( 4 ) is stable in saturated aqueous dicyclohexylamine solution, the conversion of 3 into 5 by aqueous dicyclohexylamine, reported earlier, probably involves an inversion prior to opening of the lactone ring. The behavior of 3 with aqueous dicyclohexylamine has been reinvestigated and found to produce 4 as well as 5 . With anhydrous dicyclohexylamine, 3 slowly undergoes a β-elimination to give 6 . 2-Acetamido-2-deoxy- D -gluconic acid (Scheme II, 8 ) can be prepared through the bromine—barium benzoate oxidation of 2-acetamido-2-deoxy- D -glucose, ( 7 ) but the yield is higher when bromine—cadmium carbonate is used. The acid ( 8 ) may also be made from 5 through its silver salt. The conversion of the lactone 10 into 3 through the action of anhydrous dicyclohexylamine, reported earlier, has been confirmed; the available evidence appears to indicate that 3 and the as yet uncharacterized lactone 10 are readily interconvertible under alkaline conditions. The preparation of a crystalline hydrate of 2-acetamido-2-deoxy- D -galactonic acid ( 11 ) from the corresponding dicyclohexylammonium salt is described. On dehydration in vacuo , 11 gives the known 2-acetamido-2-deoxy- D -galactono-1,4-lactone ( 12 ) in high yield.

Two benzylated hydroxyglycals derived from d-fructofuranose

Abstract 1,3,4,6-Tetra- O -benzyl- d -fructofuranosyl chloride ( 2 ), readily preparable from 1,3,4,6-tetra- O -benzyl- d -fructofuranose ( 1 ), undergoes dehydrohalogenation with ease to give two amorphous, unsaturated products (I and II). The 100-MHz p.m.r. spectra of these compounds permitted tentative assignments of structure, and these assignments were confirmed through chemical degradation. Periodate-permanganate oxidation of one of the unsaturated compounds (I) afforded 2,4-di- O -benzyl- d -erythronic acid ( 7 ), an authentic specimen of which was prepared through the periodate-hypoiodite oxidation of 3,5-di- O -benzyl- d -ribofuranose ( 8 ). This unsaturated compound is, therefore, 2,5-anhydro-1,3,4,6-tetra- O -benzyl- d - erythro -hex-2-enitol ( 3 ). Similar oxidation of the other unsaturated product (II) afforded the known 1,4-lactone of 2,3,5-tri- O -benzyl- d -arabinonic acid ( 6 ), showing that the double bond is exocyclic and that compound II is 2,5-anhydro-1,3,4,6-tetra- O -benzyl- d - arabino -hex-1-enitol ( 4 ).

5-(dimethylamino)-1-naphthalenesulfonyl (dansyl) derivatives of saccharides

Abstract 6′-O-Dansylgentiobiose, 6-O-(6-O-dansyl-β- d -galactopyranosyl)- d -galactose, and methyl 6-O-dansyl-β- d -galactopyranoside have been prepared.