First synthesis of 5,6-branched galacto-hexasaccharide,the dimer of the trisaccharide repeating unit of the cell-wall galactans of Bifidobacterium catenulatum YIT 4016

α-d-Galactopyranosyl-(1→6)-[β-d-galactofuranosyl-(1→5)]-β-d-galactofuranosyl-(1→6)-β-d-galactofuranosyl-(1→5)-[α-d-galactopyranosyl-(1→6)]-β-d-galactofuranose, the dimer of the trisaccharide repeating unit of the cell-wall galactans of Bifidobacterium catenulatum YIT 4016, has been synthesized as its dodecyl glycoside 2 by coupling of 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-[6-O-acetyl-2,3,5-tri-O-benzoyl-β-d-galactofuranosyl-(1→5)]-2-O-acetyl-3-O-benzyl-β-d-galactofuranosyl trichloroacetimidate 14 with dodecyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-[2,3,5-tri-O-benzoyl-β-d-galactofuranosyl-(1→5)]-2-O-acetyl-3-O-benzyl-β-d-galactofuranoside 16. The trisaccharide trichloroacetimidate donor 14 and trisaccharide acceptor 16 were regiospecifically prepared by employing 3-O-benzyl-1,2-O-isopropylidene-α-d-galactofuranose 4 as the glycosyl acceptor, and isopropyl 2,3,4,6-tetra-O-benzyl-1-thio-β-d-galactopyranoside 5 and 6-O-acetyl-2,3,5-tri-O-benzoyl-β-d-galactofuranosyl trichloroacetimidate 9 as glycosyl donors.     

A general method for the synthesis of oligosaccharides consisting of α-(1→2)- and α-(1→3)-linked rhamnan backbones and GlcNAc side chains

A general method has been developed for the synthesis of oligosaccharides consisting of (1→2)- and (1→3)-linked rhamnans with GlcNAc side chains. As examples, highly effective and convergent syntheses of two decasaccharides in the O polysaccharide moiety of the lipopolysaccharide of the phytopathogenic bacterium Pseudomonas syringae pv. ribicola NCPPB 1010 were achieved. The two decasaccharides consist of O polysaccharide repeating units I+II and II+I, respectively. Allyl 3-O-acetyl-4-O-benzoyl-α-l-rhamnopyranoside, allyl 2-O-benzoyl-3-O-chloroacetyl-α-l-rhamnopyranoside, 2,4-di-O-benzoyl-3-O-chloroacetyl-α-l-rhamnopyranosyl trichloroacetimidate, and 3-O-acetyl-2,4-di-O-benzoyl-α-l-rhamnopyranosyl trichloroacetimidate, which were obtained by highly regioselective 3-O-acylations, were used as the key synthons to obtain the required α-(1→2)- and α-(1→3)-linked rhamnoocta saccharide acceptors with 3³- and 3⁷-free hydroxyl groups. Therefore, several disaccharides were synthesized, from which tetrasaccharides and hexasaccharides were then synthesized. Coupling of the hexasaccharide donors with the disaccharide acceptors gave the octasaccharide acceptors. Finally, the coupling of 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl trichloroacetimidate with the octasaccharide acceptors, followed by deprotection, afforded the two target decasaccharides. A repeating hexasaccharide unit of the cell wall polysaccharide of β-hemolytic Streptococci Group A was also synthesized in a similar way.     

Synthesis of novel 5-O-(6′-O-modified)-desosamine 14-membered ketolides

A new and facile procedure was developed to synthesize novel 5-0- (6′-O-modified)-desosamine 14-membered ketolides by adopting different protective strategies and comparing various glycosylation conditions. Two trichloroacetimidate donors, with Lev or Ac substituent groups at the C-6 position, were synthesized to couple with the erythronolide. Several novel 5-0- (6′-O-modified)-desosamine 14-membered ketolides were obtained to verify the utility of the method.     

Stereoselective synthesis of α-glucosides by neighbouring group participation via an intermediate thiophenium ion

The use of a 2-O-(thiophen-2-yl)methyl protecting group allows highly stereoselective α-glucosylation of a trichloroacetimidate donor; increased stereoselectivity, presumably arising from the intramolecular formation of a transient intermediate thiophenium ion, correlates with increased bulk of the glycosyl acceptor.     

Imidomethylation of C-nucleophiles using O-phthalimidomethyl trichloroacetimidate and catalytic amounts of TMSOTf

The O-phthalimidomethyl trichloroacetimidate (1), as a latent aminomethylating agent, exhibits high electrophilicity towards a variety of C-nucleophiles in the presence of catalytic amounts of TMSOTf and mild reaction conditions. The nucleophiles include aromatics, alkenes and active methylene compounds 2-11 whereby a phthalimidomethyl group could be introduced to give compounds 12-22. Removal of the phthaloyl group gave the respective amines, β-amino ketones, and β-amino acids. The O-(trichloroacetamido)methyl trichloroacetimidate (35) was also found to be a good amidomethylating agent.     

Synthesis and conjugation of a sulfated disaccharide involved in the aggregation process of the marine sponge Microciona prolifera

The synthesis is reported of allyl (sodium 2-acetamido-2-deoxy-β-d-glucopyranosyl 3-sulfate)-(1→3)-α-l-fucopyranoside which represents an oligosaccharide fragment of the aggregation factor of the marine sponge Microciona prolifera. The title compound was obtained by coupling of 3-O-allyloxycarbonyl-2-deoxy-4,6-O-isopropylidene-2-phthalimido-β-d-glucopyranosyl trichloroacetimidate with allyl 2,4-di-O-benzoyl-α-l-fucopyranoside, followed by de-isopropylidenation, acetylation, de-allyloxycarbonylation, sulfation, de-acylation, and finally N-acetylation. The allyl glycoside was eventually converted into a 3-(2-aminoethylthio)propyl glycoside and then coupled to bovine serum albumin (BSA) using diethyl squarate as the bivalent linker, yielding 8 hapten molecules per molecule of BSA.     

Synthesis of Two Tetrasaccharides Related to the O-Antigen from Azospirillum brasilense S17 and Azospirillum lipoferum SR65

Synthesis of two isomeric tetrasaccharides, β-D-Glup-(1→2)-α-L-Rhap-(1→3)-α-L- Rhap-(1→2)-α-L-Rhap (I) and β-D-Glup-(1→3)-α-L-Rhap-(1→3)-α-L-Rhap-(1→3)-α-L-Rhap (II), the repeating units from the lipopolysaccharides of the nitrogen-fixing bacterium Azospirillum brasilense S17 and Azospirillum lipoferum SR65, was achieved via assembly of the building blocks 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl trichloroacetimidate (2), p-methoxyphenyl 3,4-di-O-benzoyl-α-L-rhamnopyranoside (3), 3-O-allyloxycarbonyl-2,4-di-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (6), 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl trichloroacetimidate (8), and p-methoxy phenyl 2,4-di-O-benzoyl-α-L-rhamnopyranoside (14). Condensation of 3 with 6 or 8 provided the disaccharides 9 or 11, respectively. Deallyloxycarbonylation of 11 gave the disaccharide aceptor 12, while removal of the p-methoxyphenyl group in 9 followed by trichloroacetimidation of the anomeric hydroxyl group afforded the disaccharide donor 10. Meanwhile, disaccharide donor 16 and acceptor 18 were prepared from 6, 8, and 14 similarly. Finally, condensation of 10 with 12 or 16 with 18, followed by deprotection, gave the target tetrasaccharides I or II, respectively.     

Efficient route to orthogonally protected precursors of 2-acylamino-2-deoxy-3-O-substituted-β-d-glucopyranose derivatives and use thereof

An efficient route to two 3-O-acyl-2-deoxy-4,6-O-isopropylidene-2-trichloroacetamido-d-glucopyranosyl trichloroacetimidate donors is reported. As demonstrated for the 3-O-acetyl derivative, these building blocks are exquisite β-d-glucosamine donors when reacted either with simple alcohols or with complex oligosaccharides. Besides, their protection pattern is compatible with selective deprotection and subsequent chain elongation at O-3 of the newly incorporated glucosamine residue.     

Chemical trans-glycosylation of bioactive glycolinkage: synthesis of an α-lycotetraosyl cholesterol

The aim of this study was to verify the antitumor role of the β-d-glucopyranosyl-(1→2)-O-[β-d-xylopyranosyl-(1→3)]-O-β-d-glucopyranosyl-(1→4)-d-galactopyranosyl (lycotetraosyl) moiety present in steroidal glycosides from Solanaceous plants. We explored a new chemical trans-glycosylation method using an endoglycosidase called tomatinase that is produced by the tomato pathogen, Fusarium oxysporum f. sp. lycopersici. The lycotetraose, which was prepared by enzymatic hydrolysis of α-tomatine with tomatinase, was converted to glycosyl donors such as trichloroacetimidate, fluoride, and thioglycoside. All obtained glycosyl donors were glycosylated with cholesterol to form α-lycotetraosyl cholesterols in a stereoselective manner. The obtained lycotetraosyl derivatives together with typical natural lycotetraosyl glycosides were examined for their antiproliferative activity.     

First synthesis of 3′-deoxy Lewisx pentasaccharide

The total synthesis of 3′-deoxy Lewis^x pentasaccharide is reported. 4-O-Acetyl-2,6-di-O-benzoyl-3-deoxy-β-d-xylo-hexopyranosyl trichloroacetimidate was condensed with a diol of glucosamine to give a disaccharide, which was further fucosylated to a Lewis^x trisaccharide analogue. Glycosylation of a lactoside diol with this trisaccharide provided a pentasaccharide, which after deprotection, afforded the target pentasaccharide.     

Stereoselective preparation of O-alkoxy d-tetrose,d-pentose, 2-deoxy-d-glycero tetrose and 2,3-dideoxy-d-erythro pentose derivatives by an iterative elongation of 2,3-O-isopropylidene-d-glyceraldehyde

All d-pentoses are synthesized by one-carbon chain elongation commencing with the addition of the lithium salt of ethyl ethylthiomethyl sulfoxide to 2-O-(t-butyldimethylsilyl)-3,4-O-isopropylidene-d-erythrose and d-threose, 16 and 17. The addition of the above-mentioned nucleophile to 2-deoxy-3,4-O-isopropylidene-d-glycero tetrose, 19, gave rise to 2,3-dideoxy-d-glycero pentose. The starting aldehydes, 16, 17 and 19, are easily available from 2,3-O-isopropylidene-d-glyceraldehyde, 1, and ethyl ethylthiomethyl sulfoxide.     

Synthesis of tryptophan N-glucoside

The naturally occurring l-tryptophan N-glucoside was synthesized using 2-O-pivaloylated glucosyl trichloroacetimidate, which gave β-N^In-glucosides. From 2-O-acetylated donors only tryptophan-1-yl-ethylidene compounds (amide acetals) were obtained. The employment of α-azido l-tryptophan benzyl ester facilitated purification and deprotection and improved the yields of the glycosylation step.     

Synthesis and asymmetric oxidation of thioglycosides derived from neomenthanethiol and α-d-galactose

6-Deoxy-6-[(1S,2S,5R)-2-isopropyl-5-methylcyclohexylsulfanyl]-1,2:3,4-di-O-isopropylidene-α-d-galactopyranose was synthesized in 94% yield from 1,2 : 3,4-di-O-isopropylidene-α-d-galactopyranose and neomenthanethiol, and its oxidation gave the corresponding diastereoisomeric sulfoxides in up to 84% yield and de values of up to 52%. The isopropylidene protective groups were removed from the sulfide and sulfoxides by treatment with trifluoroacetic acid in chloroform.     

N-Dimethylphosphoryl-protected glucosamine trichloroacetimidate as an effective glycosylation donor

Glycosylation of a variety of alcohols with 3,4,6-tri-O-acetyl-2-N-dimethylphosphoryl-2-deoxy-α-d-glucopyranosyl trichloroacetimidate as a glycosyl donor provided the corresponding coupled products in high yields and good β-selectivity. N-Dimethylphosphoryl-protection stayed stable under acidic and basic conditions for further elaboration of the glucosamine-containing oligosaccharides.     

Comparison of Several Glucuronate Glycosyl Donors

Methyl 3,4‐di‐O‐benzyl‐[(S)‐1,2‐O‐(1‐cyanoethylidene)]‐α‐d‐glucopyranuronate (12), methyl 3,4‐di‐O‐benzyl‐[(S)‐1,2‐O‐(1‐ethoxyethylidene)]‐α‐d‐glucopyranuronate (14), methyl 2‐O‐acetyl‐3,4‐di‐O‐benzyl‐α‐d‐glucopyranuronate bromide (15), methyl (2‐O‐acetyl‐3,4‐di‐O‐benzyl‐α‐d‐glucopyranosyl)uronate trichloroacetimidate (17), and methyl (2,3,4‐tri‐O‐benzyl‐α/β‐d‐glucopyranosyl)uronate trichloroacetimidate (30) were synthesized and used as glycosyl donors. Glycosylation reactions of 12 with (5‐R)‐2,3,4,5 ? tetrahydro‐5‐trityloxymethyl‐2‐furanone (32) and 14,15,17 with the corresponding (5‐R)‐2,3,4,5‐tetrahydro‐5‐hydroxymethyl‐2‐furanone (31) provided the exclusively β‐linked glucuronide 33 in 69%, 28%, 45%, and 71% yield, respectively. The coupling of donor 30 with acceptor 31 furnished the glucuronated lactone 35 in 70% yield with a surprisingly high content (20%) of the undesired α‐linked sugar residue. The structure of 33 was proved by NMR and X‐ray diffraction studies. In a model reaction a complete deprotection procedure of the glucuronic acid lactone conjugation was demonstrated.     

Synthesis of some novel sulfonyl ester derivatives derived from d-mannitol

The preparation of sulfonate-derivatives of d-mannitol i.e. 1,2:3,4-di-O-isopropylidene-3,4-di-O-p-toluenesulfonate-d-mannitol (3a), 1,2:3,4-di-O-isopropylidene-3,4-di-O-methanesulfonate-d-mannitol (3b), and 1, 2:3,4-di-O-isopropylidene-3,4-di-O-trifluoromethanesulfonate-d-mannitol (3c) is described. Full characterization and methodologies of these sulfonate-d-mannitol derivatives have been described as well.     

Efficient one-pot trans-dihydroxylation of 2H-pyrans using dimethyldioxirane (DMD): synthesis of trans-3,4-dihydroxy-3,4-dihydro-O-methyloctandreolones, orixalone D, and trans-3,4-dihydroxy-3,4-dihydromollugin natural products

An efficient one-pot formation of trans-diols on 2H-pyranyl rings was achieved by dimethyldioxirane in wet acetone. This new methodology was applied to the synthesis of natural products containing trans-diol on the pyranyl rings such as trans-3,4-dihydroxy-3,4-dihydro-O-methyloctandreolones, orixalone D, and trans-3,4-dihydroxy-3,4-dihydromollugin.     

Insights for diastereoselective synthesis of cyclic α-sulfinyl and sulfanyl oximes

The comparison in several reaction conditions for synthesis of nonracemic α-methylsulfinylation of 3,4-dihydronaphthalen-1(2H)-one was achieved. The sulfanylation reactions of 3,4-dihydronaphthalen-1(2H)-one-O-methyloxime and 2-(methylsulfinyl)-3,4-dihydronaphthalen-1(2H)-one-O-methyloxime by homogenous reaction medium are reported. The products were obtained in good yields and de. The yields, diastereoselectivity and theoretical calculations to all obtained compounds to support the experimental data are compared and discussed.     

Synthesis and epimerization of 10-N-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl)-(11aS)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-dione

The reaction of the 1,2:3,4-di-O-isopropylidene-6-O-tosyl-α-d-galactopyranose 2 with (11aS)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-dione 1, prepared from l-proline and isatoic anhydride, gave two products which were previously reported as conformational isomers. In this work, an X-ray crystallographic study showed these to be the diastereomeric pair (11aS)- and (11aR)-10-N-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl)-pyrrolo[2,1-c][1,4]benzodiazepin-5,11-diones as a consequence of C(11a) epimerization in the benzodiazepine moiety during glycosylation under basic reaction conditions. The hydrosolubility of the deprotected products were compared with those of the analogous benzodiazepine derivatives.     

l-Ascorbic acid in organic synthesis: DBU-catalysed one-pot synthesis of tetramic acid derivatives from 5,6-O-isopropylidene ascorbic acid

Reaction of 5,6-O-isopropylidene-2,3-bis-O-alkyl ascorbic acid with different amines in the presence of DBU at ambient temperature resulted in the formation of 3,4-bis-O-alkyl-1-alkyl-5-(2-hydroxy ethyl)-5-hydroxy-1,5-dihydropyrrol-2-ones in moderate yields.