The structure and properties of the products of reaction between 3,4,6-tri-O-acetyl-2-deoxy-2-nitroso-α-d-galactopyranosyl chloride and pyrazole

Dimeric 3,4,6-tri-O-acetyl-2-deoxy-2-nitro-α-d-galactopyranosyl chloride reacts with pyrazole in acetonitrile to give 1-(3,4,6-tri-O-acetyl-2-deoxy-2-hydroxyimino-α-d-lyxo-, -β-d-lyxo-, and -β-d-xylo-hexopyranosyl)pyrazole. The stereospecificity of the reaction depends on the temperature and its duration. Transformations of the type α-d-lyxo-←β-d-lyxoα β-d-xylo have been observed. The condensation products were modified at C-2 or C-3. The following derivatives have thus been obtained: 1-(α-d-galacto-, 2-acetamido-2-deoxy-α-d-galacto-, -α-d-talo-, and -α-d-xylo-hexo-pyranosyl)pyrazole, (Z)- and (E)-1-(3-azido-2,3-dideoxy-2-hydroxyimino-α- and -β-d-lyxo- and -α-d-xylo-hexopyranosyl)pyrazole, 1-(3-acetamido-2-acetoxyimino-4,6-di-O-acetyl-2,3-dideoxy-α- and -β-d-lyxo-hexopyranosyl)pyrazole, as well as (Z)- and (E)-1-(2,3-dideoxy-2-hydroxyimino-α-d-threo-hexopyranosyl)pyrazoles.     

1,5-anhydro-2-deoxy-3-O-(2-deoxy-beta-D-arabino-hexopyranosyl)-D-arabino-hex-1-enitol, the by-product in the enzymic hydration of D-glucal by beta-D-glucosidase from emulsin.

The by-product (3) in the hydration of D-glucal (1) catalyzed by emulsin beta-D-glucosidase has been identified as 1,5-anhydro-2-deoxy-3-O-(2-deoxy-beta-D-arabino-hexopyranosyl)-D-arabino-hex-1-enitol. Two models for the formation of 3 are discussed, involving transfer of a 2-deoxy-D-arabino-hexopyranosyl cation to HO-3 of D-glucal (glycon transfer) and transfer of an allylic D-pseudoglucal cation to HO-1 of 2-deoxy-D-arabino-hexopyranose (aglycan transfer). The enzymic production of 3 is highly regiospecific, which lends support to the second model and implies the presence of a specific binding-site for the aglycon moiety.     

Equimolar oxymercuration of D-glucal triacetate with mercuric perchlorate and its application to the synthesis of 2′-deoxy disaccharides

A search for appropriate reaction conditions for the equimolar methoxymercuration of D-glucal triacetate was made by using various mercuric salts, bases, and reaction solvents. Under optimum conditions with mercuric perchlorate, sym-collidine, and acetonitrile, D-glucal triacetate underwent methoxymercuration with an equimolar amount of methanol to afford methyl 3,4,6-tri-O-acetyl-2-deoxy-2-perchloratomercuri-β-D-glucopyranoside (1, 26%) and its α-D-manno isomer (2, 49%). Equimolar oxymercuration of D-glucal triacetate with partially protected sugars, followed by subsequent demercuration of the products with sodium borohydride, afforded α- and β-linked 2′-deoxy disaccharide derivatives in moderate yields. The partially protected sugars used were 1,2,3,4-tetra-O-acetyl-β-D-glucopyranose and 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose, and the corresponding products were O-(3,4,6-tri-O-acetyl-2-deoxy-α-D-arabino-hexopyranosyl)-(1→6)-1,2,3,4-tetra-O-acetyl-D-glucopyranose(4, 23%) and its β-linked isomer (5, 11%) from the former, and O-(3,4,6-tri-O-acetyl-2-deoxy-α-D-arabino-hexapyranosyl)-(1→6)-1,2:3,4-di- O-isopropylidene-α-D-galactopyranose (9, 29%) and its β-linked isomer (10, 10%) from the latter. Deacetylation of these 2′-deoxy disaccharides was effected with methanolic sodium methoxide, but deacetonation was unsuccessful owing to simultaneous cleavage of the glycosidic linkage.     

Ketodeoxyhexosylpurines. Synthesis and properties of keto derivatives of 7-(beta-L-fucopyranosyl)-theophylline

Catalytic fusion of 1,2,3,4-tetra-O-acetyl-L-fucose with theophylline gave 7-(2,3,4-tri-O-acetyl-6-deoxy-β-L-galactopyranosyl)theophylline (1) which was deacetylated with sodium methoxide to give 7-(6-deoxy-β-L-galactopyranosyl)theophylline (2), further transformed by selective condensation with acetone into 7-(6-deoxy-3,4-O-isopropylidene-β-L-galactopyranosyl)theophylline (3). Oxidation of 3 employing a modified Pfitzner-Moffatt procedure led to 7-(6-deoxy-3,4-O-isopropylidene-β-L-lyxo-hexopyranosulosyl)theophylline (5). However, treatment of 3 with dimethyl sulfoxide-acetic anhydride according to the procedure used for deoxy hexoses gave only the 2′-O-acetyl analog 4. Treatment of 5 with alkali showed it to be more stable than 2′-ketouridine or 2′-ketocytidine. Finally, in vivo biological assays showed that 7-(6-deoxy-β-L-lyxo-hexopyranosulosyl)theophylline (7) inhibits cellular growth, whereas the nucleoside 2 is inactive before oxidation.     

Ring-opening reactions of sucrose epoxides: Synthesis of 4′-derivatives of sucrose

The 2,1′-O-isopropylidene derivative (1) of 3-O-acetyl-4,6-O-isopropylidene-α-d-glucopyranosyl 6-O-acetyl-3,4-anhydro-β-d-lyxo-hexulofuranoside and 2,3,4-tri-O-acetyl-6-O-trityl-α-d-glucopyranosyl 3,4-anhydro-1,6-di-O-trityl-β-d-lyxo-hexulofuranoside have been synthesised and 1 has been converted into 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,6-di-O-acetyl-3,4-anhydro-β-d-lyxo-hexulofuranoside (2). The S_N2 reactions of 2 with azide and chloride nucleophiles gave the corresponding 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-azido-4-deoxy-β-d-fructofuranoside (6) and 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-chloro-4-deoxy-β-d-fructofuranoside (8), respectively. The azide 6 was catalytically hydrogenated and the resulting amine was isolated as 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 4-acetamido-1,3,6-tri-O-acetyl-4-deoxy-β-d-fructofuranoside. Treatment of 5 with hydrogen bromide in glacial acetic acid followed by conventional acetylation gave 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,3,6-tri-O-acetyl-4-bromo-4-deoxy-β-d-fructofuranoside. Similar S_N2 reactions with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl 1,6-di-O-acetyl-3,4-anhydro-β-d-ribo-hexulofuranoside (12) resulted in a number of 4′-derivatives of α-d-glucopyranosyl β-d-sorbofuranoside. The regiospecific nucleophilic substitution at position 4′ in 2 and 12 has been explained on the basis of steric and polar factors.     

The structure of the O-glycosylically-linked oligosaccharide chains of LPG-I,a glycoprotein present in articular lubricating fraction of bovine synovial fluid

Periodate oxidation of LPG-1 established that N-acetylneuraminic acid residues are linked preponderantly α-(2→3) to D-galactose residues. The resistance of 2-acetamido-2-deoxyD-galactose residues to periodate oxidation suggests that they are linked at either O-3 or O-4 to D-galactose residues. After treatment of LPG-I with alkaline sulfite, ≈80% of 2-acetamido-2-deoxygalactose was recovered as the sulfonic acid derivative. The Gal→GalNAc disaccharide released from sialic-acid-free LPG-I by digestion with endo-2-acetamido-2-deoxy-α-D-galactosidase (which suggests an α-D-GalNAc→-L-Ser or -L-Thr linkage) gave a high color-yield in the Morgan—Elson reaction, indicating that 2-acetamido-2-deoxy-D-galactose residues are linked at C-3 to D-galactose residues. The migration of the released Gal-GalNAc disaccharide was the same as that of a standard sample of O-β-D-galactosyl-(1→3)-2-acetamido-2-deoxy-D-galactose. Treatment of sialic acid-free LPG-I with Streptococcus pneumoniae β-D-galactosidase, which hydrolyzes only galactosides linked β-D-(1→4) gave no free D-galactose, whereas treatment of LPG-I with bovine testes β-D-galactosidase released > 90% of D-galactose. These results provide evidence for β-D-Galp-(1→3)-α-D-GalNAcp-(1→3)-L-Ser or -L-Thr and α-NeuAc-(2→3)-β-D-Galp-(1→3)-α-D- GalNAcp-(1→3)-L-Ser or -L-Thr structures. The sensitivity of the methods used and the recovery of constituents following treatment of LPG-I do not rule out the occurrence of small amounts of other tri- or tetra-saccharide chains.     

2-acetamido-2-deoxy-α-D-galactosidases of clostridium perfringens. separation and characterization of an exoglycosidase and an oligosaccharidase

Two distinct 2-acetamido-2-deoxy-α-D-galactosidases have been separated from filtrates of cultured Clostridium perfringens by electrophoresis in 6.5% poly(acryl-amide) gels. One of the enzymes had a mobility of 0.32-0.36 (relative to Bromophenol Blue) and was identified as the exoglycosidase, 2-acetamido-2-deoxy-α-D-galactosidase. It appears to be the same enzyme as that reported in 1972 by McGuire et al. The second of the two ezymes, having a relative mobility of 0.42-0.46, corresponds to the oligosaccharidase reported in 1972 by Huang and Aminoff. The A-specificities of human type-A erythrocytes and of water-soluble glycoproteins having A-activity are both destroyed by incubation with the 2-acetamido-2-deoxy-α-D-galactosidase, but not on incubation with the oligosaccharidase. A concomitant rise in blood-group O(H) activity, as indicated by the use of a lectin from Ulex europeus, occurred in the A-erythrocytes treated with the exoglycosidase 2-acetamido-2-deoxy-α-D-galactosidase.     

Stereochemistry of D-galactal and D-galacto-octenitol hydration by coffee bean alpha-galactosidase: insight into catalytic functioning of the enzyme.

Green coffee bean alpha-galactosidase was found to catalyze the hydration of D-galactal and (Z)-3,7-anhydro-1,2-dideoxy-D-galacto-oct-2-enitol (D-galacto-octenitol), each a known substrate for beta-galactosidase. The hydration of D-galactal by the alpha-galactosidase in D2O yielded 2-deoxy-2(S)-D-[2-2H]galactose; the hydration of D-[2-2H]galacto-octenitol in H2O yielded 1,2-dideoxy-2(R)-D-[2-2H]galactooct-3-ulose. Thus, the enzyme protonated each substrate from beneath the plane of the ring, as assumed for alpha-D-galactosides. These results provide an unequivocal assignment of the orientation of an acidic catalytic group to the alpha-galactosidase reaction center. In addition, they reveal a pattern of glycal/exocyclic enitol/glycoside protonation by the enzyme that differs from the pattern reported for beta-galactosidase and from that reported for alpha-glucosidases. Further findings show that D-galacto-octenitol is hydrated by the coffee bean alpha-galactosidase to form the alpha-anomer of 1,2-dideoxy-D-galactooctulose and by Escherichia coli beta-galactosidase to form the beta-anomer. That each enzyme converts this enolic substrate to a product whose de novo anomeric configuration matches that formed from its D-galactosidic substrates provides new evidence for the role of protein structure in controlling the steric outcome of reactions catalyzed by these and other glycosylases. The findings are discussed in light of the concept that catalysis by glycosidases involves a "plastic" protonation phase and a "conserved" product configuration phase.     

A substrate for the fluorogenic assay of exo-beta-N-acetylmuramidase: synthesis and purification of 4-methylumbelliferyl N-acetylmuramide.

A fluorogenic substrate for exo-β-N-acetylmuramidase from Bacillus subtilis B was synthesized. 4-Methyl-2-oxo-1,2-benzopyran-7-yl 2-acetamido-4,6-O-benzylidene-2-deoxy-β-d-glucopyranoside was prepared from 4-methyl-2-oxo-1,2-benzopyran-7-yl 2-acetamido-2-deoxy-β-d-glucopyranoside, condensed with dl-2-chloropropionic acid, the benzylidene residue removed by acetolysis and the 4-methyl-2-oxo-1,2-benzopyran-7-yl 2-amino-3-O-(d-1-carboxyethyl)-2-deoxy-β-d-glucopyranoside purified by chromatography on silica gel and Sephadex G-10 and by high-voltage paper electrophoresis. The identity of the product was confirmed by pmr studies, acid hydrolysis followed by chromatography of the products, and enzymic digestion.     

Studies on cellulolytic enzymes I: The use of 3,4-dinitrophenyl glycosides as substrates

The syntheses of 3,4-dinitrophenyl β-d-glucoside, β-cellobioside, β-cellotrioside, and β-cellotetraoside and their use to monitor the purification of two enzymes from a crude commercial cellulase preparation from Trichoderma viride are described. The enzymes isolated are an endo-β-1,4-d-glucan glucanohydrolase (EI) of molecular weight ca. 12 000 which catalysed the release of 3,4-dinitrophenol from 3,4-dinitrophenol-β-cellotetraoside, and an enzyme of molecular weight about 76 000 which catalysed the hydrolysis of 3,4-dinitrophenyl β-d-glucoside (EII) and is probably a cellobiase or exo-β-1,4-d-glucan glucohydrolase. Kinetic parameters are reported for the hydrolyses of 3,4-dinitrophenyl β-cellobioside, β-cellotrioside, and β-cellotetraoside catalysed by enzyme EI. In the presence of cellotriose, cellotetraose, or cellopentaose 3,4-dinitrophenyl β-d-glucoside underwent induced hydrolyses by EI. Similar but faster induced hydrolyses were shown by 3,4-dinitrophenyl β-d-xyloside and 3,4-dinitrophenyl β-d-6-deoxyglucoside; 3,4-dinitrophenyl 6-chloro-6-deoxy-β-d-glucoside and 3,4-dinitrophenyl 6-O-methyl-β-d-glucoside underwent slower induced hydrolyses than the glucoside. p-Nitrophenyl β-d-glucoside also underwent an induced hydrolysis in the presence of cellopentaose and the enzyme EI, but p-nitrophenyl 2-deoxy-β-d-glucoside did not. These results are discussed and compared with the results obtained previously on induced hydrolyses found with lysozyme. Kinetic parameters are reported for the hydrolysis of 3,4-dinitrophenyl and p-nitrophenyl β-d-glucosides catalysed by the enzyme EII. 3,4-Dinitrophenyl 6-deoxy-β-d-glucoside, β-d-xyloside, 6-chloro-6-deoxy-β-d-glucoside, 6-O-methyl-β-d-glucoside and p-nitrophenyl-β-d-galactopyranoside and 2-deoxy-β-d-glucopyranoside were hydrolysed 10² to 10³ times slower by EII than the corresponding glucosides, but 3,4-dinitrophenyl 2-acetamido-2-deoxy-β-d-glucoside was only hydrolysed about 25 times slower than 3,4-dinitrophenyl β-d-glucoside. The significance of these results is discussed. EII catalysed the release of 3,4-dinitrophenol from 3,4-dinitrophenyl β-cellobioside, β-cellobioside, and β-cellotetraoside, but these reactions showed induction periods which are consistent with stepwise removal of glucose residues from the oligosaccharide chains before release of the phenol.     

A surprising C-4 epimerization of 5-deoxy-5-sulfonylated pentofuranosides under Ramberg-Bäcklund reaction conditions

Treatment of methyl 5-deoxy-2,3-O-isopropylidene-5-(benzylsulfonyl)-β-d-ribofuranoside with CBr₂F₂-KOH/Al₂O₃ afforded the corresponding olefinic sugar. The methyl- and the isopropyl-analogues in contrast underwent epimerization at C-4 to generate the α-l-lyxo derivatives.     

Synthesis of di-, tri-, and tetra-saccharides corresponding to receptor structures recognised by Streptococcus pneumoniae

Syntheses are described for methyl 2-acetamido-2-deoxy-4-O-β-d-galactopyranosyl-α-d-glucopyranoside, methyl 2-acetamido-2-deoxy-4-O-β-d-galactopyranosyl-β-d-glucopyranoside, methyl 3-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl-β-d-galactopyranoside, methyl 3-O-(2-acetamido-2-deoxy-4-O-β-d-galactopyranosyl-β-d-glucopyranosyl)-β-d-galactopyranoside, and methyl 4-O-[3-O-(2-acetamido-2-deoxy-4-O-β-d-galactopyranosyl-β-d-glucopyranosyl)-β-d-galactopyranosyl]- β-d-glucopyranoside.     

Acid-catalysed monoacetalation of some 2-deoxyalditols

Acid-catalysed monobutylidenation of 2-deoxy-D-arabino-hexitol, 2-deoxy-D-lyxo-hexitol, and 2-deoxy-D-erythro-pentitol yielded a 1,3-monoacetal as a kinetic product in each reaction. The thermodynamic products were 4,6-monoacetals from 2-deoxy-D-arabino-hexitol and 2-deoxy-D-lyxo-hexitol, and a 3,5-monoacetal from 2-deoxy-D-erythro-pentitol 2-Deoxy-D-lyxo-hexitol also yielded diastereoisomeric 4,5-monoacetals.     

Synthesis of 2-deoxy-2-fluorohexoses by fluorination of glycals in aqueous media

1,5-Anhydro-2-deoxy-d-arabino- (d-glucal), 1,5-anhydro-2-deoxy-d-lyxo- (d-galactal), and 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-d-lyxo-hex-1-enitol (3,4,6-tri-O-acetyl-d-galactal) (3) were fluorinated in water and organic solvent-water with molecular fluorine and, for ¹⁸F-labelled compounds, with [¹⁸F]fluorine. Chemical yields of 40 and 10% were obtained for 2-deoxy-2-fluoro-d-glucose and 2-deoxy-2-fluoro-d-mannose, respectively, and 35 and 5% for 2-deoxy-2-fluoro-d-galactose (12) and 2-deoxy-2-fluoro-d-talose (13), respectively. In the fluorination of 3, the chemical yields of 12 and 13 were 38 and 6%, respectively. An l.c. separation of 2-deoxy-2-fluoro-d-hexoses is described.     

A convenient synthesis of 1,2-O-benzylidene and 1,2-O-ethylidene derivatives of carbohydrates

N.m.r., enzymic, and chemical techniques have been used to characterise the d-galactose-containing tri- and tetra-saccharides produced on hydrolysis of carob and L. leucocephalad-galacto-d-mannans by Driselase β-d-mannanase. These oligosaccharides were shown to be exclusively 6¹-α-d-galactosyl-β-d-mannobiose and 6¹-α-d-galactosyl-β-d-mannotriose. Furthermore, these were the only d-galactose-containing tri- and tetra-saccharides produced on hydrolysis of carob d-galacto-d-mannan by β-d-mannanases from other sources, including Bacillus subtilis, Aspergillus niger, Helix pomatia gut solution, and germinated legumes. Acid hydrolysis of lucerne galactomannan yielded 6¹-α-d-galactosyl-β-d-mannobiose and 6²-α-d-galactosyl-β-d-mannobiose.     

Depolymerization of heparin with diazomethane. Structure of N,O-methylated,even-numbered oligosaccharides produced by β-eliminative cleavage of the 2-amino-2-deoxyglycosylic linkage

The long-period reaction of heparin with excess diazomethane at 20° resulted in cleavage at the β-position of the uronic acid carboxyl group to give a mixture of methyl α- and β-glycosides of N,O-methylated di-, tetra-, and hexa-saccharides having a 4,5-unsaturated uronic acid, nonreducing end-group. The major disaccharides obtained were methyl O-(4-deoxy-3-O-methyl-α-l-threo-hex-4-enopyranosyluronic acid 2-sulfate)-(1→4)-2-deoxy-3-O-methyl-2-(N-methylsulfoamino)-α- and -β-d-glucopyranoside. The reaction of heparin at 4° yielded a mixture of methylated, higher-molecular-weight oligosaccharides, which retained some affinity for antithrombin III-Sepharose.     

O-glycosylhydrolases of embryos of the sea urchin <Emphasis Type="Italic">Strongylocentrotus intermedius</Emphasis> and effect of some natural substances on their biosynthesis

Embryos of the sea urchin Strongylocentrotus intermedius have been found to contain o-glycosyl hydrolases: highly active 1,3-β-D-glucanase and β-D-mannosidase as well as a lower activity of β-D-glucosidase and β-D-galactosidase. Dynamics of changes of the enzyme activities has been studied at various stages of the sea urchin development. There has also been studied effects of some substances (natural fucoidans, β-1.3; 1.6-glucans formed by enzymatic synthesis as well as protein inhibitor of marine mollusc endo-1,3-β-D-glucanases) on development of the embryos and biosynthesis of 1,3-β-D-glucanase and α-D-mannosidase.     

Addition of halogenoazides to glycals

Addition of chloroazide to 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-d-lyxo- (1) and -d-arabino-hex-1-enitol (2) under u.v. irradiation proceeds regio- and stereo-selectively yielding mainly O-acetyl derivatives of 2-azido-2-deoxy-d-galactopyranose and -d-glucopyranose, respectively. 3,4,6-Tri-O-acetyl-2-chloro-2-deoxy-α-d-galactopyranosyl azide and 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α-d-talopyranose (from 1), and 1,3,4,6-tetra-O-acetyl-2-chloro-2-deoxy-α-d-glucopyranosyl azide and 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-α-d-mannopyranose (from 2) are byproducts. 1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy-d-lyxo- and -d-arabino-hex-1-enitol reacted more rapidly with chloroazide, to give, under irradiation, derivatives of 2-azido-2-deoxy-d-galactose and -d-glucose, respectively. However, reaction in the dark gave mainly O-benzyl derivatives of 2-chloro-2-deoxy-α-d-galacto- and -α-d-glucopyranosyl azide. The difference between the products obtained may depend on the existence of two parallel processes, one radical (under irradiation), and the other ionic (reaction in the dark).     

Synthesis of an intensely sweet chlorodeoxysucrose: Mechanism of 4′-chlorination of sucrose by sulphuryl chloride

Reaction of 6-O-acetylsucrose¹ with sulphuryl chloride in chloroform-pyridine affords, after dechlorosulphation and acetylation, a mixture of two isomeric 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-d-galactopyranosyl 3-O-acetyl-1,4,6-trichloro-1,4,6-trideoxy-β-d-hexulofuranosides (6 and 7) and 2,3,6-tri-O-acetyl-4-chloro-4-deoxy-α-d-galactopyranosyl 3,4-di-O-acetyl-1,6-dichloro-1,6-dideoxy-β-d-fructofuranoside (4). Chlorination of C-4, C-1′, and C-6′ occurs by direct displacement of the initially formed chlorosulphonyloxy groups by chloride ions, but displacement of the 4′-chlorosulphate is sterically hindered. The introduction of a 4′-chloro substituent involves ring opening of intermediate 3′,4′-epoxides by chloride ions, the ribo-epoxide producing the sorbo-isomer 6 and the lyxo-epoxide giving the fructo-isomer 7. The proposed mechanism is supported by the formation of 4-chloro-4-deoxyfructofuranosides when 3′,4′-lyxo-hexulofuranosides are treated with sulphuryl chloride under the same conditions.     

Synthesis of 1-β-L-Arabinofuranosylcytosine (β-L-Ara-C) and 2′-Deoxy-2′-methylene-β-L-cytidine (β-L-DMDC) as Potential Antineoplastic Agents

Abstract

1-β-L-Arabinofuranosylcytosine (β-L-Ara-C, 7) and 2′-deoxy-2′-methylene-β-L-cytidine (β-L-DMDC, 14) have been synthesized via a multi-step synthesis from L-arabinose. These compounds were tested in vitro against L1210, P388, Sarcoma 180, and CEM cells, and found not to be active at a concentration up to 100 μM. β-L-Ara-C and β-L-DMDC were also tested against HSV-1 and HSV-2 and yielded ID₅₀ values of 100 μM.