Preparation of New Glycoheptofurano[2,1-d]Imidazolidine-2-Thiones., Isomerizations to Acyclic-Sugar C-Nucleoside Analogues of Imidazole

Abstract

1-Methyl- and 1-aryl-(1,2-dideoxy-D-glyofurano)[2,1-d]-imidazolidine-2-thiones having the configurations β-D-glycero-L-gluco (4), β-D-glycero-D-ido (5—8), α-D glycerol-D-galacto (9—10) and β-D-glycero-D-talo (11, 12) are prepared by reaction of 2-amino-2-deoxy-aldoses with methyl and aryl isothiocyanates. 1-Aryl-(1,2-dideoxy–β-D-glycero-L-gluco-heptofurano)[2,1-d]imidazolidine-2-thiones (1—3) have been converted into 1-aryl-4-(D-galacto-pentitol-1-yl)-4-imidazo-line-2-thiones (24—26) by acid catalysed isomerization.     

Preparation of 1-aryl-2-(benzylthio)-(1,2-dideoxy-d-glycero-β-l-gluco-heptofurano)[1,2-d]-2-imidazolines,and new,acyclic C-nucleosides of the imidazole

The reaction of 1-aryl-(1,2-dideoxy-d-glycero-β-l-gluco-heptofurano)[1,2-d]imidazolidine-2-thiones with benzyl chloride and an equivalent amount of sodium hydrogencarbonate yields 1-aryl-2-(benzylthio)-(1,2-dideoxy-d-glycero-β-l-gluco-heptofurano)[1,2-d]-2-imidazolines (2). If the reaction is carried out in the absence of sodium hydrogencarbonate, the 1-aryl-2-(benzylthio)-4-(d-galacto-pentitol-1-yl)imidazoles are obtained. These compounds are also obtained by acid-catalyzed isomerization of compounds 2.     

Synthesis of p-nitrophenyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-mannopyranoside

The reaction of p-nitrophenyl 2,3-O-isopropylidene-α-d-mannopyranoside and 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)-[2,1-d]-2-oxazoline gave a crystalline, 6-O-substituted disaccharide derivative which, on de-isopropylidenation followed by saponification, produced the disaccharide p-nitrophenyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-mannopyranoside. Synthesis of methyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-mannopyranoside was also accomplished by a similar reaction-sequence. The structures of these disaccharides have been established by ¹³C-n.m.r. spectroscopy.     

Synthesis of 1,3,4,6-tetra-O-acetyl-2-[3-alkyl-(aryl)-thioreido]-2-deoxy-α-d-glucopyranoses and their transformation into 2-alkyl(aryl)amino-(1,2-dideoxy-α-d-glucopyrano)[2,1-d]-2-thiazolines

1,3,4,6-Tetra-O-acetyl-2-deoxy-2-isothiocyanato-α-d-glucopyranose, produced from 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-α-d-glucopyranose hydrochloride, thiophosgene, and calcium carbonate, was condensed with alkyl- and aryl-amines in ether to afford the crystalline 1,3,4,6-tetra-O-acetyl-2-[3-alkyl(aryl)-thioureido]-2-deoxy-α-d-glucopyranoses (2). Compounds 2 and the β anomers 3 were converted in high yield into 2-alkyl(aryl)amino-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)[2,1-d]-2-thiazoline hydrobromides (4) by hydrogen bromide-promoted cyclisation. The O-deacetylated thiazoline hydrobromide 5 was also isolated and converted into 2-[N-(4-methoxyphenyl)acetamido]-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)[2,1-d]-2-thiazoline (8). Conformational studies of 4 and 8 were made by ¹H-n.m.r. spectroscopy.     

The synthesis and properties of benzylated oxazolines derived from 2-acetamido-2-deoxy-D-glucose

2-Methyl-(2-acetamido-3,4,6-tri-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline,2-methyl-(2-acetamido-6-O-acetyl-3,4-di-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline,and 2-methyl-(2-acetamido-4-O-acetyl-3,6-di-O-benzyl-1,2-dideoxy-α-D-glucopyrano)-[2,1-d]-2-oxazoline were synthesized from the allyl 2-acetamido-3,4,6-tri-O-benzyl-2-deoxy-D-glucopyranosides, and from the 3,4-di-O-benzyl or 3,6-di-O-benzyl analogs, respectively, both the α and β anomer being used in each case. The preparation of allyl 2-acetamido-3,4,6-tri-O-benzyl- and 3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside is also described. Treatment of the tri-O-benzyl oxazoline with dibenzyl phosphate gave a pentabenzylglycosyl phosphate, from which all the benzyl groups were removed by catalytic hydrogenation, giving 2-acetamido-2-deoxy-α-D-glucopyranosyl phosphate. The corresponding β anomer was not detectable. Treatment of the 3,4-, or 3,6-, di-O-benzyl oxazoline with allyl 2-acetamido-3,4-di-O-benzyl-α-D-glucopyranoside readily gave disaccharide products from which the protecting groups were removed, to give the (1→6)-linked isomer of di-N-acetylchitobiose. Under both acidic and basic conditions, this isomer was less stable than the (1→4)-linked compound.Attempts to employ the 3,6-di-O-benzyl oxazoline for the formation of (1→4)-linked disaccharides, by treatment with either anomer of allyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-D-glucopyranoside, were not very successful, presumably owing to hindrance by the bulky benzyl groups.     

A green expedient synthesis of pyridopyrimidine-2-thiones and their antitubercular activity

The pseudo four-component domino reactions of N-substituted-4-piperidones, substituted aromatic aldehydes and thiourea in the presence of solid sodium ethoxide under solvent-free conditions afforded pyridopyrimidine-2-thiones in almost quantitative yields by simply grinding for 1-2 min. at ambient temperature. The synthesized compounds were screened for their in vitro activity against Mycobacterium tuberculosis H37Rv. Among them, (E)-6-benzyl-8-(2,4-dichlorobenzylidene)-4-(2,4-dichlorophenyl)-3,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidine-2(1H)-thione (MIC 2.8 μM) displays the maximum activity, being 2.7 and 1.7 times more active than the first line antitubercular drugs ethambutol and ciprofloxacin, respectively, and less active than rifampicin and isoniazid, by 28 and 7 times, respectively.     

Synthesis and anti-proliferative activity of a small library of 7-substituted 5H-pyrrole [1,2-a][3,1]benzoxazin-5-one derivatives

In this study, we investigate the anti-proliferative activity of a small library of 7-substituted 5H-pyrrolo[1,2-a][3,1]benzoxazin-5-one derivatives, against a panel of human cancer cell lines. We reported the synthesis of these compounds in a previous work. 7-Bromo-5H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-5-one showed a promising anti-proliferative effect. As starting material for Suzuki-Miyaura cross coupling reaction, it was selected for the design and the synthesis of six further derivatives, with the aim to better define structure-activity relationships. The anti-proliferative MTT assay revealed a dose-dependent reduction of cell viability, especially for 7-([1,1′-biphenyl]-4-yl)-5H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-5-one. Cell cycle and western blotting analysis suggested apoptosis as possible mechanism for its anti-proliferative activity. These preliminary results encourage our interest for further optimizations.     

Improved preparations of some per-O-acetylated aldohexopyranosyl cyanides

3,4,6-Tri-O-acetyl-1,2-O-[1-(exo-, endo-cyano)ethylidene]-α-d-galacto- (1a/b), -α-d-gluco- (2a/b), and -β-d-manno-pyranose (3a/b) were stereoselectively isomerized to the corresponding per-O-acetylated 1,2-trans-aldohexopyranosyl cyanides in 75, 16, and 62% yield, respectively, by treatment with boron trifluoride etherate in dry nitromethane. The corresponding per-O-acetylated 1,2-cis-aldohexopyranosyl cyanides were obtained concurrently in respective yields of 1.9, 0.9, and 4.8%. The per-O-acetylaldohexopyranosyl cyanide products were found stable to the reaction conditions and were readily isolated following completion of the rearrangement. It had previously been proved that reaction of 2,3,4,6-tetra-O-acetyl-α-d-manno- and -gluco-pyranosyl bromide with mercuric cyanide in nitromethane generates, in the ratio of ∼1:1, the desired 1,2-trans-glycosyl cyanides and the corresponding 1,2-O-(1-cyanoethylidene) isomers (3a/b and 2a/b, respectively). Treatment of these reaction-mixtures with boron trifluoride etherate in nitromethane effected the rearrangement of 3a/b and 2a/b, thereby facilitating the isolation, and increasing the overall yields, of the per-O-acetylated 1,2-trans-d-manno and -gluco-pyranosyl cyanides (58 and 30% total yield, respectively) relative to the earlier procedures. The boron trifluoride etherate-mediated reaction of per-O-acetyl-α- and -β-d-galacto, -α- and -β-d-gluco-, -α-d-manno-, and -2-deoxy-2-phthalimido-β-d-gluco-pyranoses with trimethylsilyl cyanide in nitromethane was also investigated. This reaction provides a “one-flask” synthesis of the corresponding per-O-acetylated 1,2-trans-aldohexopyranosyl cyanides in which 1,2-O-(1-cyanoethylidene) derivatives are isomerized in situ. Finally, improved preparations of the (not readily accessible) per-O-acetylated 1,2-cis-d-manno- and -gluco-pyranosyl cyanides are described. Thus, 2,3,4,6-tetra-O-acetyl-α- and -β-d-mannopyranosyl cyanide (48 and 16% total yield, respectively) and -α- and -β-d-glucopyranosyl cyanide (12 and 39% total yield, respectively) were synthesized by fusion of the corresponding -α-d-glycosyl bromides with mercuric cyanide.     

Synthesis,characterization, and antimicrobial evaluation of some new hydrazinecarbothioamide, 1,2,4-triazole and 1,3,4-thiadiazole derivatives

In this work, we reported the synthesis and evaluation of antibacterial and antifungal activities of three new compound series obtained from 6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazole-3-acetic acid hydrazide: 2-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetyl}-N-alkyl/arylhydrazinecarbothioamides (2a–d), 4-alkyl/aryl-2,4-dihydro-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-3H-1,2,4-triazole-3-thiones (3a–n), and 2-alkyl/arylamino-5-{[6-(phenyl/4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]methyl}-1,3,4-thiadiazoles (4a–g). The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR (APT), mass and elemental analysis. Their antibacterial and antifungal activities were evaluated against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Candida albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, Trichophyton mentagrophytes var. erinacei NCPF 375, Microsporum gypseum NCPF 580, and T. tonsurans NCPF 245. 3c, 3f, 3m, 3n, and 4e showed the highest antibacterial activity. Particularly 3c, 3f, 3g, 3k, 3n, 4a, 4e, and 4g showed the highest antifungal activity against tested fungi.     

Design,synthesis and biological evaluation of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives as Mycobacterium tuberculosis pantothenate synthetase inhibitors

In the present study, we have designed imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives from earlier reported imidazo[1,2-a]pyridine based Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS) inhibitors. We synthesized thirty compounds and they were evaluated for MTB PS inhibition study, in vitro anti-TB activities against replicative and non-replicative MTB, in vivo activity using Mycobacterium marinum infected Zebra fish and cytotoxicity against RAW 264.7 cell line. Among them compound 2-methyl-N′-(4-phenoxybenzoyl)benzo[d]imidazo[2,1-b]thiazole-3-carbohydrazide (5bc) emerged as potent compound active against MTB PS with IC₅₀ of 0.53 ± 0.13 μM, MIC of 3.53 μM, 2.1 log reduction against nutrient starved MTB, with 33% cytotoxicity at 50 μM. It also showed 1.5 log reduction of M. marinum load in Zebra fish at 10 mg/kg.     

ω-Aminoalkyl β-glycosides of N-acetylmuramyl-l-alanyl-d-isoglutamine,and their conjugates with meningococcal group C polysaccharide

The 6-aminohexyl β-glycoside of N-acetylmuramyl-l-alanyl-d-isoglutamine and its spacer-arm-linked analog (3.8 nm) were synthesized from 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)-[2,1-d]-2-oxazoline, and coupled with meningococcal group C polysaccharide in attempts to enhance the immunogenicity of the polysaccharide antigen.     

Molecular Cloning and Functional Characterization of Components of the Capsule Biosynthesis Complex of Neisseria meningitidis Serogroup A: TOWARD IN VITRO VACCINE PRODUCTION*

The human pathogen Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis and sepsis globally. A major virulence factor of Nm is the capsular polysaccharide (CPS), which in Nm serogroup A consists of N-acetyl-mannosamine-1-phosphate units linked together by phosphodiester linkages [→6)-α-d-ManNAc-(1→OPO₃⁻→]_n. Acetylation in O-3 (to a minor extent in O-4) position results in immunologically active polymer. In the capsule gene cluster (cps) of Nm, region A contains the genetic information for CPSA biosynthesis. Thereby the open reading frames csaA, -B, and -C are thought to encode the UDP-N-acetyl-d-glucosamine-2-epimerase, poly-ManNAc-1-phosphate-transferase, and O-acetyltransferase, respectively. With the aim to use a minimal number of recombinant enzymes to produce immunologically active CPSA, we cloned the genes csaA, csaB, and csaC and functionally characterized the purified recombinant proteins. If recombinant CsaA and CsaB were combined in one reaction tube, priming CPSA-oligosaccharides were efficiently elongated with UDP-GlcNAc as the donor substrate, confirming that CsaA is the functional UDP-N-acetyl-d-glucosamine-2-epimerase and CsaB the functional poly-ManNAc-1-phosphate-transferase. Subsequently, CsaB was shown to transfer ManNAc-1P onto O-6 of the non-reducing end sugar of priming oligosaccharides, to prefer non-O-acetylated over O-acetylated primers, and to efficiently elongate the dimer of ManNAc-1-phosphate. The in vitro synthesized CPSA was purified, O-acetylated with recombinant CsaC, and proven to be identical to the natural CPSA by ¹H NMR, ³¹P NMR, and immunoblotting. If all three enzymes and their substrates were combined in a one-pot reaction, nature identical CPSA was obtained. These data provide the basis for the development of novel vaccine production protocols.     

Discovery of pentacyclic compounds as potent inhibitors of hepatitis C virus NS5B RNA polymerase

We report a new series of inhibitors for hepatitis C virus NS5B RNA polymerase containing a constrained pentacyclic scaffold. Our SAR studies led to the identification of hexahydroindolo[2,1-a]pyrrolo[3,2-d][2]benzazepines exposing basic groups. The compounds displayed a high activity in the enzyme assay and displayed good activity in the cell-based (replicon) assay in the presence of serum proteins.     

The synthesis of P1-2-acetamido-4-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2-deoxy-α-d-glucopyranosyl P2-dolichyl pyrophosphate, (P1-di-N-acetyl-α-chitobiosyl P2-dolichyl pyrophosphate)

2-Acetamido-4-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2-deoxy-α-d-glucopyranosyl phosphate, pure according to thin-layer and gas—liquid chromatography, optical rotation, and treatment with alkaline phosphatase and 2-acetamido-2-deoxy-β-d-glucosidase, was prepared by treatment of 2-methyl-[4-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-acetyl-1,2-dideoxy-α-d-glucopyrano]-[2,1-d]-2-oxazoline with dibenzyl phosphate, followed by the removal of the benzyl groups by catalytic hydrogenolysis, and O-deacetylation. In contrast, a sample prepared by the phosphoric acid procedure was shown to consist mainly of the β anomer. 2-Acetamido-4-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-acetyl-2-deoxy-α-d-glucopyranosyl phosphate was treated wit P¹-diphenyl P²-dolichyl pyrophosphate to give a fully acetylated pyrophosphoric diester, which was O-deacetylated to give P¹-2-acetamido-4-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2-deoxy-α-d-glucopyranosyl P²-dolichyl pyrophosphate. This compound could be separated from the β anomer by t.l.c., and its behavior under dilute acid and alkaline conditions was investigated.     

Syntheses of 3-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-galactopyranose (“lacto-N-biose II”) and 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-d-galactopyranose

3- O-(2-Acetamido-2-deoxy-β-d-glucopyranosyl)-α-d-galactopyranose (10, “Lacto-N-biose II”) was synthesized by treatment of benzyl 6-O-allyl-2,4-di-O-benzyl-β-d-galactopyranoside with 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)[2,1-d]-2-oxazoline (5), followed by selective O-deallylation, O-deacetylation, and catalytic hydrogenolysis. Condensation of 5 with benzyl 6-O-allyl-2-O-benzyl-α-d-galactopyranoside, followed by removal of the protecting groups, gave 10 and a new, branched trisaccharide, 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-d-galactopyranose (27).     

Structural modification of 3-arylisoquinolines to isoindolo[2,1-b]isoquinolinones for the development of novel topoisomerase 1 inhibitors with molecular docking study

Isoindolo[2,1-b]isoquinolinones 9a–i were designed and synthesized as constrained forms of 3-arylisoquinolines through an intramolecular cyclization reaction. Among the synthesized compounds, 9d exhibited potent topoisomerase 1 inhibitory activity with cytotoxicities against three different tumor cell lines. A Surflex-dock docking study was performed to clarify the topoisomerase 1 inhibitory activity of 9d.     

Synthesis of benzyl 2-acetamido-2-deoxy-3-O-β-d-fucopyranosyl-α-d-galactopyranoside and benzyl 2-acetamido-6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2-deoxy-3-O-β-d-fucopyranosyl-α-d-galactopyranoside

Condensation of benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-d-galactopyranoside with 2,3,4-tri-O-acetyl-α-d-fucopyranosyl bromide in 1:1 nitromethane-benzene, in the presence of powdered mercuric cyanide, afforded benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4-tri-O-acetyl-β-d-fucopyranosyl)-α-d-galactopyranoside (3). Cleavage of the benzylidene group of 3 with hot, 60% aqueous acetic acid afforded diol 4, which, on deacetylation, furnished the disaccharide 5. Condensation of diol 4 with 2-methyl-(3,4,6-tri-O-acetyl-1,2-di-deoxy-α-d-glucopyrano)-[2,1-d]-2-oxazoline in 1,2-dichloroethane afforded the trisaccharide derivative (7). Deacetylation of 7 with Amberlyst A-26 (OH^?) anion-exchange resin in methanol gave the title trisaccharide (8). The structures of 5 and 8 were confirmed by ¹³C-n.m.r. spectroscopy.     

Imidazo[2′,1′:2,3]thiazolo[4,5-d]pyridazinone as a new scaffold of DHFR inhibitors: Synthesis,biological evaluation and molecular modeling study

New series of thiazolo[4,5-d]pyridazin and imidazo[2′,1′:2,3]thiazolo[4,5-d]pyridazin analogues were designed, synthesized and evaluated for their in vitro DHFR inhibition and antitumor activity. Compounds 13 and 43 proved to be DHFR inhibitors with IC₅₀ 0.05 and 0.06 μM, respectively. 43 proved lethal to OVCAR-3 Ovarian cancer and MDA-MB-435 Melanoma at IC₅₀ 0.32 and 0.46 μM, respectively. The active compounds formed hydrogen bond at DHFR binding site between N₁-nitrogen of the pyridazine ring with Glu30; the carbonyl group with Trp24, Arg70 or Lys64; π-cation interaction with Arg22 and π-π interaction with Phe31 residues. Ring annexation of the active 1,3-thiazole ring analogue 13 into the bicyclic thiazolo[4,5-d]pyridazine (18,19) or imidazo[2,1-b]thiazoles (23–25) decreased the DHFR inhibition activity; while the formation of the tricyclic imidazo[2′,1′:2,3]-thiazolo[4,5-d]pyridazine (43–54) increased potency. The obtained model could be useful for the development of new class of DHFR inhibitors.     

Synthesis of carbon-11-labeled CK1 inhibitors as new potential PET radiotracers for imaging of Alzheimer’s disease

The reference standards methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate (5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide (5c), and their corresponding desmethylated precursors 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoic acid (6a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-hydroxybenzamide (6b), were synthesized from 5-amino-2,2-difluoro-1,3-benzodioxole and 3-substituted benzoic acids in 5 and 6 steps with 33% and 11%, 30% and 7% overall chemical yield, respectively. Carbon-11-labeled casein kinase 1 (CK1) inhibitors, [¹¹C]methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate ([¹¹C]5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-[¹¹C]methoxybenzamide ([¹¹C]5c), were prepared from their O-desmethylated precursor 6a or 6b with [¹¹C]CH₃OTf through O-[¹¹C]methylation and isolated by HPLC combined with SPE in 40–45% radiochemical yield, based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740?GBq/μmol with a total synthesis time of ～40-min from EOB.     

Unusual properties of glycuronans [poly(glycosyluronic) compounds]

2-Methyl-[3,6-di-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-α-d-glucopyrano]-[2,1-d]-2-oxazoline (4) was prepared from 2-acetamido-3,6-di-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-α-d- glucopyranosyl chloride. Condensation of 3,4:5,6-di-O-isopropylidene-d-mannose dimethyl acetal with 4 in the presence of a catalytic amount of p-toluenesulfonic acid afforded O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-(1 → 4)-O-(2-acetamido-3,6-di-O-acetyl-2-deoxy-β-d-glucopyranosyl)-(1 → 2)-3,4:5,6-di-O-isopropylidene-d-mannose dimethyl acetal (6) in 8.6% yield. Catalytic deacetylation of 6 with sodium methoxide, followed by hydrolysis with dilute sulfuric acid, gave O-β-d-galactopyranosyl-(1 → 4)-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1 → 2)-d-mannose (7). The inhibitory activities of 7 and related sugars against the hemagglutinating activities of various lectins were assayed, and 7 was found to be a good inhibitor against Phaseolus vulgaris hemagglutinin.