Photoreaction of methyl 4,6-O-benzylidene-2,3-dideoxy-3-nitro-β-d-erythro-hex-2-enopyranoside with 1,3-dioxolane and tetrahydrofuran

Irradiation of the title compound in 1,3-dioxolane and in tetrahydrofuran respectively afforded the d-gluco and d-manno isomers having the 1,3-dioxolan-2-yl and tetrahydrofuran-2-yl group at C-2, besides the glycosid-3-ulose and nitro alcohol; in the later case, the dimer was also isolated.     

Preparation and structural determination of methyl 4,6-O-benzylidene-2,3-dideoxy-β-d-erythro-hexopyranosid[2,3-d]triazole and of its adducts with 3-nitrohex-2-enopyranosides

A 3-nitrohex-2-enopyranoside whose C-1 atom was mostly deuterated was prepared from (1S)-1,5-anhydro-d-(1,²H)glucitol and subjected to an addition reaction with methyl 4,6-O-benzylidene-2,3-dideoxy-β-d-erythro-hexopyranosid-[2,3-d]-triazole, derived from the nitro alkene with lithium azide. The structure of the adducts was, by ¹H-n.m.r. spectroscopy, assigned the d-gluco configuration for the nitro sugar moiety.     

Synthesis and reactions of 1′,2:4,6-di-o-isopropylidene-sucrose

The reaction of sucrose with a combination of 2,2-dimethoxypropane, N,N-dimethylformamide, and toluene-p-sulphonic acid (reagent A) gave, after acetylation followed by chromatography, 1′,2:4,6-di-O-isopropylidenesucrose tetra-acetate (1) in 15% yield. The structure of 1 was determined on the basis of p.m.r. and mass spectrometry, and by chemical transformations. Treatment of 1 with aqueous acetic acid afforded sucrose 3,3′,4′,6′-tetra-acetate 2. Reacetalation of 2 using reagent A gave 1 in 80% yield. The p.m.r. spectrum of 2 confirmed the presence of hydroxyl groups at C-2 and C-4. The following sequence of reactions showed that the remaining two hydroxyl groups were located at C-6 and C-1′. Selective tritylation of 2 gave 1′,6-di-O-tritylsucrose 3,3′,4′,6′-tetra-acetate (3) as the minor, and 6-O-tritylsucrose 3,3′,4′,6′-tetra-acetate (4) as the major, product. When tritylation was carried out under forcing conditions, 2 gave 3 as the major product. Acetylation of 4 afforded 6-O-tritylsucrose hepta-acetate. Mesylation of 2 gave the tetramethanesulphonate 5, which afforded the 6-dcoxy-6-iodo derivative 6 on treatment with a refluxing solution of sodium iodide in butanone. Treatment of 3 with methanesulphonyl chloride in pyridine gave the disulphonate 7, which on detritylation followed by acetylation gave 2,4-di-O-methanesulphonylsucrose hexa-acetate (9). Treatment of 9 with sodium benzoate in hexamethylphosphoric triamide displaced the 4-sulphonate, with inversion of configuration, to give the galacto derivative 10.     

New syntheses of methyl 4,6-O-benzylidene-2-deoxy-3-C-methyl-α-d-arabino-hexopyranoside and its conversion into d-evermicose

Methyl 4,6-O-benzylidene-2-deoxy-3-C-methyl-α-d-arabino-hexopyranoside (4) was prepared from methyl 4,6-O-benzylidene-2,3-dideoxy-3-C-methylene-α-d-erythro-hexopyranoside (1b) and from methyl 4,6-O-benzylidetic-3 C-methyl-α-d-gluco-hexopyranoside (6a) by two different methods. Synthesis of d-evermicose3 (10 (2,6-dideoxy-3-C-methyl-d-arabino-hexose) was then achieved in four steps from 4.     

A concise synthesis of methyl 2,6-dideoxy-2-fluoro-β-l-talopyranoside

The 4,6-benzylidene acetal of methyl 2-deoxy-2-fluoro-α,β-d-glucopyranoside underwent inversion at C-3 via an oxidation–reduction sequence, and treatment of the derived 3-acetate with N-bromosuccinimide in carbon tetrachloride gave methyl 3-O-acetyl-4-O-benzoyl-6-bromo-2,6-dideoxy-2-fluoro-α-d-allopyranoside (6). Dehydrobromination of 6 and reduction of the resultant 5,6-ene gave the 5-epimer of 6, which after removal of the ester substituents, afforded the title compound in good overall yield.     

Addition of hydrazoic acid to methyl 6-O-benzoyl-2,3-dideoxy-α-D-glycero-hex-2-enopyranosid-4-ulose

The title compound 4 reacted with hydrazoic acid to give exclusively an adduct having the threo configuration, whose structure was established by reduction to the lyxo derivatives 8 and 10. The reaction of 4 with hydrogen peroxide afforded the epoxide 12, the lyxo structure of which was deduced by conversion into the alcohol 13. Tributylborane also reacted with the enone 4, giving the adduct 15, whose configuration was tentatively assigned to be threo.     

Photochemical addition of 2-propanol and of acetone to methyl 5-deoxy-2,3-O-isopropylidene-β-d-erythro-pent-4-enofuranoside

High-capacity adsorbents for lectins, including Lotus tetragonolobusl-fucose-binding protein, were readily prepared by conjugation of monosaccharides with commercially available, epoxy-activated Sepharose. Purified, radioiodinated lectins were bound to cells of the mosquito Aedes aegyptii and of human KB tumour. Relative to human KB cells, mosquito cells bound less of lectins specific for the sugars (l-fucose and d-galactose) that are terminal residues in many mammalian glycoproteins, whereas the number of binding sites of lectins specific for core-region sugars (d-mannose and 2-acetamido-2-deoxy-d-glucose) were similar. Neuraminidase, which greatly enhanced binding of peanut agglutinin or soybean agglutinin to human KB cells, had negligible effects on binding of these lectins to mosquito cells. The comparative structures of surface oligosaccharides of mosquito and KB cells are discussed in relation to the lectin-binding studies.     

The preparation of 4,6-dichloro-4,6-dideoxy-α-d-galactopyranosyl 6-chloro-6-deoxy-,β-d-fructofuranoside and the conversion of chlorinated derivatives into anhydrides

Under carefully controlled conditions, sucrose is converted by selective reaction with sulphuryl chloride into either 6-chloro-6-deoxy-α-d-glucopyranosyl 6-chloro-6-deoxy-β-d-fructofuranoside or 4,6-dichloro-4,6-dideoxy-α-d-galactopyranosyl 6-chloro-6-deoxy-β-d-fructofuranoside, which could be isolated without recourse to chromatography. Treatment of the dichloride with sodium methoxide gave 3,6-anhydro-β-d-glucopyranosyl, 3,6-anhydro-β-d-fructofuranoside in high yield. In contrast, 4,6-dichloro-4,6-dideoxy-α-d-galactopyranosyl 6-chloro-6-deoxy-β-d-fructofuranoside gave, in two distinct stages, 3,6-anhydro-4-chloro-4-deoxy-α-d-galactopyranosyl 6-chloro-6-deoxy-β-d-fructofuranoside and 3,6-anhydro-4-chloro-4-deoxy-α-d-galactopyranosyl 3,6-anhydro-β-d-fructofuranoside. The structures of these products were ascertained by ¹H-n.m.r. and mass spectrometry.     

Synthesis and cytotoxic analysis of some disodium 3β,6β-dihydroxysterol disulfates

Disodium 3β,6β-dihydroxy-5α-cholestane disulfate (1) was synthesized in 4 steps with a high overall yield from cholesterol. First, cholesterol (4a) was converted to cholest-4-en-3,6-dione (5a) via oxidation with pyridinium chlorochromate (PCC) and then 5a was reduced by NaBH₄ in the presence of NiCl₂ to produce cholest-3β,6β-diol (6a). The reaction of 6a with the triethylamine-sulfur trioxide complex generated diammonium 3β,6β-dihydroxy-5α-cholestane disulfate (7a) and the treatment of 7a by cation exchange resin 732 (sodium form)(Na⁺) yielded the target steroid 1. Disodium 24-ethyl-3β,6β-dihydroxycholest-22-ene disulfate (2) and disodium 24-ethyl-3β,6β-dihydroxycholestane disulfate (3) were synthesized using a similar method. The cytotoxicity of these compounds against Sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells was investigated. Our results indicate that presence of a cholesterol-type side chain at position 17 is necessary for their biological activity.     

Synthesis and anti-tumor activities of methyl 2-O-aryl-6-O-aryl′-d-glucopyranosides

A synthetic method of introducing bulky aryl groups at the 2-O- and 6-O-positions on glucopyranosides was developed. A total of 37 new compounds of this class were obtained successfully. These compounds were tested on several tumor cell lines by MTT assays, and some of them exhibited encouraging inhibitory activities. The most potent compound, CAB-SHZH-27, exhibited EC₅₀ values of 14, 12, and 10 μmol/L on A549, MDA-MB-231 and HeLa cells, respectively. A preliminary structure–activity relationship analysis indicates that the two free hydroxyl groups on the d-glucose core are indispensable for the biological activities of this class of compounds, and the aryl group at the 6-O-position has a more obvious impact than the one at the 2-O-position. An interesting ‘on–off’ mechanism of this class of compounds was also observed in our MTT assays, which remains to be explored.     

Synthesis of benzyl and methyl 3-benzamido-2,3,6-trideoxy-2-fluoro-β-l-galactopyranoside: Protected C-2 fluoro analogues of daunosamine

The reaction of benzyl 2-benzamido-4,6-O-benzylidene-2-deoxy-3-O-tosyl-α-d-glucopyranoside or benzyl 4,6-O-benzylidene-2,3-benzoylepimino-2,3-dideoxy-α-d-allopyranoside with anhydrous tetrabutylammonium fluoride in hexamethylphosphoric triamide gave ∼40% of benzyl 3-benzamido-4,6-O-benzylidene-2,3-dideoxy-2-fluoro-α-d-altropyranoside (6a). Transformation of 6a into benzyl 3-benzamido-2,3,6-trideoxy-2-fluoro-α-d-arabino-hex-5-enopyranoside (13a) was carried out by well-established methodology. Hydrogenation of the double bond in 13a furnished the title compound in good yield. Methyl 3-benzamido-2,3,6-trideoxy-2-fluoro-β-l-galactopyranoside was also prepared in nine steps from 2-amino-2-deoxy-d-glucose.     

Chemical-Enzymatic Synthesis of 3′-Amino-2′, 3′-dideoxy-β-D-ribofuranosides of Natural Heterocyclic Bases and Their 5′-Monophosphates

Abstract

Treatment of O², 3′-anhydro-5′-O-trityl derivatives of thymidine (1) and 2′-deoxyuridine (2) with lithium azide in dimethylformamide at 150 °C resulted in the formation of the corresponding isomeric 3′-azido-2′, 3′-dideoxy-5′-O-trityl-β-D-ribofuranosyl N¹- (the major products) and N³-nucleosides (3/4 and 5/6). 3′-Amino-2′, 3′-dideoxy-β-D-ribofuranosides of thymidine [Thd(3′NH₂)], uridine [dUrd(3′NH₂)], and cytidine [dCyd(3′NH₂)] were synthesized from the corresponding 3′-azido derivatives. The Thd(3′NH₂) and dUrd(3′NH₂) were used as donors of carbohydrate moiety in the reaction of enzymatic transglycosylation of adenine and guanine to afford dAdo(3′NH₂) and dGuo(3′NH₂). The substrate activity of dN(3′NH₂) vs. nucleoside phosphotransferase of the whole cells of Erwinia herbicola was studied.