Carla Marino

Deoxy sugars: occurrence and synthesis.

Publisher Summary This chapter describes the occurrence and synthesis of deoxy sugars. Several deoxy sugars, notably 2-deoxy- D -erythro-pentose (2-deoxy- D -ribose)—the sugar component of DNA, 6-deoxy- L -mannose ( L -rhamnose), 6-deoxy- L -galactose ( L -fucose), 6-deoxy- D -glucose (quinovose), and their derivatives, occur very widely in natural product. The iodo and bromo derivatives of monosaccharides can be reduced by a variety of reducing agents to afford the corresponding deoxy sugar. The more stable chloro derivatives can be reduced with Raney nickel. Selective reduction of a secondary chloride with respect to a primary chloride may be achieved if the reduction is performed in the presence of triethylamine. Mesylates or tosylates may be reduced directly or through the intermediate halides or epoxides. Epoxides are involved in the reduction of tosylates by lithium aluminum hydride or lithium triethyl borohydride. A general method for the synthesis of 2-deoxyaldoses utilizes a reaction sequence involving the formation and subsequent reduction of ketene dithioacetal intermediates.

Facile Synthesis of per-O-tert-Butyldimethylsilyl-β-d-galactofuranose and Efficient Glycosylation via the Galactofuranosyl Iodide

The synthesis of crystalline per-O-TBS-beta-D-galactofuranose (4beta) as a new precursor of D-Gal f units is described. Anomeric iodination by reaction with TMSI followed by in situ coupling with simple alcohols and a wide variety of glycosyl acceptors, in the absence of a promoter, was employed as a new efficient glycosylation method for the assembly of D-galactofuranosyl moieties with high beta-stereoselectivity. Under the mild conditions of this reaction labile protective groups, like acetals, and furanosyl linkages are preserved.

Convenient syntheses of 5-O- and 3,5-di-O-(β-d-galactofuranosyl)-d-galactofuranose

Abstract Benzoylation of d -galactono-1,4-lactone with 2.2 mol of benzoyl chloride, at −23°, gave the 2,6-dibenzoate ( 2 , 62%). Tin(IV) chloride-catalyzed glycosylation of 2 with 1,2,3,5,6-penta- O -benzoyl-α,β- d -galactofuranose ( 1 ) afforded 2,6-di- O -benzoyl-5- O -(2,3,5,6-tetra- O -benzoyl-β- d -galactofuranosyl)- d -galactono-1,4-lactone ( 4 , 70%), HO-3 of which was benzoylated to give 5 . The structure of 4 was confirmed by its conversion into crystalline β- d -Gal f -(1→5)- d -Gal-ol ( 8 ). Reduction of the lactone function of 5 with di-isoamylborane followed by debenzoylation gave β- d -Gal f -(1→5)- d -Gal f ( 7 ). A by-product of the condensation of 1 with 2 was characterized as 2,6-di- O -benzoyl-3,5-di- O -(2,3,5,6-tetra- O -benzoyl-β- d -galactofuranosyl)- d -galactono-1,4-lactone ( 9 ), which was converted, as for 5 , into β- d -Gal f -(1→3)[β- d -Gal f -(1→5)]- d -Gal f ( 13 ).

ACIDS AND OTHER PRODUCTS OF OXIDATION OF SUGARS

Publisher Summary This chapter focuses on the low-molecular weight carbohydrates that can be formally considered as the oxidation products of mono- or oligo-saccharides in which an aldehyde group and/or one or more hydroxyl groups have been oxidized to carbonyl and/or carboxyl groups. Some acids are important natural products, for instance, L -ascorbic acid (vitamin C); others, such as the glycuronic acids, are the constituents of abundant polysaccharides. Examples of commercial importance are ascorbic acid, as one of the major water-soluble antioxidants; salts of gluconic acid such as the magnesium salt used in the pharmaceutical industry; and D -ribono-1,4-lactone, a versatile material used in the synthesis of natural products. The oxidation products are divided into two principal categories,—namely, acids (and lactones) and neutral compounds. Three kinds of sugar acids can be formally obtained from the corresponding aldoses: (1) aldonic acids, produced by the oxidation at C–1 of the aldose; (2) uronic acids, formed by the oxidation of the primary alcohol group of the aldose; and (3) aldaric acids, formed by the oxidation of both the aldehyde and the primary alcohol group. Neutral oxidation products such as dialdoses, glycosuloses, and glycodiuloses are also discussed in detail in the chapter.

Immobilized 4-aminophenyl 1-thio-β-d-galactofuranoside as a matrix for affinity purification of an exo-β-d-galactofuranosidase

An alternative and fast method for the purification of an exo-beta-D-galactofuranosidase has been developed using a 4-aminophenyl 1-thio-beta-D-galactofuranoside affinity chromatography system and specific elution with 10 mM D-galactono-1,4-lactone in a salt gradient. A concentrated culture medium from Penicillium fellutanum was chromatographed on DEAE-Sepharose CL 6B followed by chromatography on the affinity column, yielding two separate peaks of enzyme activity when elution was performed with 10 mM D-galactono-1,4-lactone in a 100-500 mM NaCl salt gradient. Both peaks behaved as a single 70 kDa protein, as detected by SDS-PAGE. Antibodies elicited against a mixture of the single bands excised from the gel were capable of immunoprecipitating 0.2 units out of 0.26 total units of the enzyme from a crude extract. The glycoprotein nature of the exo-beta-D-galactofuranosidase was ascertained through binding to Concanavalin A-Sepharose as well as by specific reaction with Schiff reagent in Western blots. The purified enzyme has an optimum acidic pH (between 3 and 6), and Km and Vmax values of 0.311 mM and 17 mumol h-1 microgram-1 respectively, when 4-nitrophenyl beta-D-galactofuranoside was employed as the substrate.

Synthesis of 4-nitrophenyl β-d-fucofuranoside and β-d-fucofuranosyl-(1→3)-d-mannopyranose: modified substrates for studies on catalytic requirements of β-d-galactofuranosidase

Abstract Syntheses of 4-nitrophenyl β- d -fucofuranoside ( 6 ) and β- d -fucofuranosyl-(1→3)- d -mannopyranose ( 10 ) are reported. These compounds, as analogues of galactofuranosides, were used for studying the influence of the hydroxyl group at C-6 in the interaction of the substrate with β- d -galactofuranosidase. For the synthesis of the fucofuranosides, 2,3,5-tri- O -benzoyl-6-bromo-6-deoxy- d -galactono-1,4-lactone ( 1 ) was the key intermediate, which upon reduction of the lactone group with diisoamylborane, acetylation of the anomeric hydroxyl group, and catalytic hydrogenolysis of the bromine at C-6, led to 1- O -acetyl-2,3,5-tri- O -benzoyl-α,β- d -fucofuranose ( 4 ), a convenient derivative for the preparation of fucofuranosides. Compound 4 was glycosylated in the presence of SnCl 4 , either with 4-nitrophenol for the preparation of 6 , or with 2,5,6-tri- O -benzoyl- d -mannono-1,4-lactone ( 7 ), for the synthesis of disaccharide 10 , via the glycosyl-aldonolactone approach. The synthetic route developed for the β- d -fucofuranosides is simple and efficient. Compound 6 was not hydrolyzed by incubation with the exo β- d -galactofuranosidase from Penicillium fellutanum , showing that HO-6 is essential for interaction of the substrate with the enzyme.

The glycosyl-aldonolactone approach for the synthesis of β-d-Galf-(1→3)-d-Manp and 3-deoxy-β-d-xylo-hexofuranosyl-(1→3)-d-Manp

A convenient synthesis of free beta-D-Galf-(1-->3)-D-Manp (8a) is reported. The disaccharide is present as external unit in the lipopeptidophosphoglycan (LPPG) of Trypanosoma cruzi and internally in the lipophosphoglycan (LPG) of Leishmania. Condensation of 2,5,6-tri-O-benzoyl-D-mannono-1,4-lactone (1) with 1,2,3,5,6-penta-O-benzoyl-D-galactofuranose, promoted by SnCl4, led to the beta-glycosyl-lactone, a key intermediate for disaccharide 8a, readily obtained by successive reduction of the lactone with diisoamylborane and debenzoylation. As in the LPG of Leishmania the HO-3 group of the galactofuranose is glycosylated by alpha-D-Galp, we also synthesized 3-deoxy-beta-D-xylo-hexofuranosyl-(1-->3)-D-Manp (8b) and p-nitrophenyl 3-deoxy-beta-D-xylo-hexofuranoside for studying the influence of HO-3 in the interaction with specific glycosidases. The disaccharide 8a, and its corresponding alditol, were good substrates for the beta-D-galactofuranosidase from Penicillium fellutanum, whereas the 3-deoxyglycosides were not hydrolyzed by the enzyme.

FACILE SYNTHESIS OF GLYCOFURANOSYL ISOTHIOCYANATES

Abstract Peracylated glycofuranosyl isothiocyanates are obtained under smooth conditions starting from the corresponding glycosyl chloride by reaction with potassium thiocyanate in anhydrous acetone at room temperature, classical conditions for the synthesis of glycopyranosyl thiocyanates. In the case of furanoses, no glycosyl thiocyanates are obtained, and the procedure leads to the 1,2- trans isothiocyanates, stereoselectively, with over 80% yield.

Thiodisaccharides with galactofuranose or arabinofuranose as terminal units: Synthesis and inhibitory activity of an exo β-d-galactofuranosidase

Thiodisaccharides having beta-D-Galf or alpha-L-Araf units as non-reducing end have been synthesized by the SnCl(4)- or MoO(2)Cl(2)-promoted thioglycosylation of per-O-benzoyl-D-galactofuranose (1), its 1-O-acetyl analogue 4, or per-O-acetyl-alpha-L-arabinofuranose (16) with 6-thioglucose or 6-thiogalactose derivatives. After convenient removal of the protecting groups, the free thiodisaccharides having the basic structure beta-D-Galf(1-->6)-6-thio-alpha-D-Glcp-OMe (5) or beta-D-Galf(1-->6)-6-thio-alpha-D-Galp-OMe (15) were obtained. The respective alpha-L-Araf analogues 18 and 20 were prepared similarly from 16. Alternatively, beta-D-Galf(1-->4)-4-thio-3-deoxy-alpha-L-Xylp-OiPr was synthesized by Michael addition to a sugar enone of 1-thio-beta-d-Galf derivative, generated in situ from the glycosyl isothiourea derivative of 1. The free S-linked disaccharides were evaluated as inhibitors of the beta-galactofuranosidase from Penicillium fellutanum, being 15 and 20 the more active inhibitors against this enzyme.

Reactions of per-O-benzoyl-β-D-Galf isothiocyanate, a chiral resolving agent

Abstract Tetra- O -benzoyl- β -D-galactofuranosyl isothiocyanate ( 1 ) was readily prepared (90% yield) from per- O -benzoyl-D-galactofuranose, via the glycosyl bromide. Reaction of 1 with alcohols, amines and amino acids afforded a variety of glycosylthiourethanes and glycosylthioureides. The isothiocyanate 1 showed to be useful as a chiral resolving agent. The resolution of racemic primary and secondary amines and aminoalcohols was readily accomplished, in analytical and preparative scale, by condensation of such compounds with 1 .