Preparation of 2-Azido-4-O-benzoyl-2,6-dideoxy-3-O-methyl-β-D-allopyranose and Its Disaccharide Derivative

Abstract

2-Azido-4-O-benzoyl-2,6-dideoxy-3-O-methyl-D-allopyranose, needed as one of the building blocks for construction of a novel cyclodextrin-like compound, was prepared in the form of crystalline β-anomer 6 from methyl 2-azido-4,6-O-benzylidene-2-deoxy-α-D-allopyranoside 1. As a model of α-glycosidation necessary for formation of a cyclic structure, 6 was converted into the corresponding β-glycosyl trichloroacetimidate and coupled with methyl 6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoside 8, giving α(1→4)-linked disaccharide derivative 9.     

Direct synthesis of pyrrole nucleosides by the stereospecific sodium salt glycosylation procedure

A stereospecific high-yield glycosylation of preformed fully aromatic pyrroles has been accomplished for the first time. Reaction of the sodium salt of pyrrole-2-carbonitrile ( 1a ) and pyrrole-2,4-dicarbonitrile ( 1b ) with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose ( 2 ) gave exclusively the corresponding blocked nucleosides with β-anomeric configuration 3a and 3b , which on deprotection gave 1-(2-deoxy-β-D-erythro-pentofuranosyl) derivatives of 1a ( 3c ) and 1b ( 3d ). Functional group transformation of 3c and 3d provided a number of 2-monosubstituted 4a-c and 2,4-disubstituted 4d-f derivatives of 1-(2-deoxy-β-D-erythro-pentofuranosyl)pyrrole. Similar glycosylation of the sodium salt of 1a and 1b with 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose ( 5 ) and further functional group transformation of the intermediate blocked nucleosides 6a and 6b provided 1-β-D-arabinofuranosyl derivatives of pyrrole-2-carboxamide ( 7b ) and pyrrole-2,4-dicarboxamide ( 7d ). The synthetic utility of this glycosylation procedure for the preparation of 1-β-D-ribofuranosylpyrrole-2-carbonitrile ( 12 ) has also been demonstrated by reacting the sodium salt of 1a with 1-chloro-2,3-O-isopropylidene-5-O-(t-butyl)dimethylsilyl-α-D-ribofuranose ( 10 ) and subsequent deprotection of the blocked intermediate 11 . This study provided a convenient route to the preparation of aromatic pyrrole nucleosides.     

2-Deoxy-2-C-(2,3-dideoxy-α-d-erythro-hexopyranosyl)-β-d-glucopyranoses: Reinvestigation of Synthesis,Use in Glycosylation,and Conformational Analyses by NMR

Abstract

Conformational investigations using 1D TOCSY and ROESY ¹H NMR experiments on 1,3,4,6-tetra-O-acetyl-2-C-(4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hexopyranosyl)-2-deoxy-β-D-glucopyranose (8) and related disaccharides showed that for steric reasons the C-linked hexopyranosyl ring occurs in the usually unfavoured ¹C₄ conformation and reconfirmed the structure of 1,3,4,6-tetra-O-acetyl-2-C-(4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosyl)-2-deoxy-β-D-glucopyranose (5). Glycosylation of 2,3,6-tri-O-benzyl-α-D-glucopyranosyl 2,3-di-O-benzyl-4,6-(R)-O-benzylidene-α-D-glucopyranoside (13) with acetate 8 using trimethylsilyl triflate as a catalyst afforded the α-D-linked tetrasaccharide 14. A remarkable side product in this reaction was the unsaturated tetrasaccharide 2,3,6-tri-O-benzyl-4-O-[4,6-di-O-acetyl-2,3-dideoxy-2-C-(4,6-di-O-acetyl-2,3-dideoxy-β-D-erythro-hexopyranosyl)-α-D-erythro-hex-2-enopyranosyl]-α-D-glucopyranosyl 2,3-di-O-benzyl-4,6-(R)-O-benzylidene-α-D-glucopyranoside (16) where in the C-linked hexopyranosyl ring an isomerization to the β-anomer had taken place to allow for the favoured ⁴C₁ conformation. The tetrasaccharide 14 was deacetylated and hydrogenolyzed to form the fully deprotected tetrasaccharide 18. The ¹ C ₄ conformation of the C-glycosidic pyranose of this tetrasaccharide was maintained as shown by an in depth NMR analysis of its peracetate 19.     

Enantiomeric composition of the chiral constituents in essential oils. Part 1: Monoterpene hydrocarbons

Using a dual column gas chromatograph equipped with two capillary columns coated with heptakis(6-O-methyl-2,3-di-O-pentyl)-β-cyclodextrin (6-me-2,3-pe-β-CD) and octakis(6-O-methyl-2,3-di-O-pentyl)-γ-cyclodextrin (6-me-2,3-pe-γ-CD), respectively, all important olefinic monoterpene hydrocarbons occurring in essential oils, including α-thujene, α- and β-pinene, camphene, sabinene, α- and β-phellandrene, Δ-3-carene and limonene can be resolved into enantiomers. With the chromatographic system described the characteristic enantiomeric composition of these monoterpene hydrocarbons in essential oils can be determined.     

Nucleic acid related compounds. 81. Syntheses of 9-(3-deoxy-β-D-threo-pentofuranosyl)adenine,the core nucleoside of the extraordinarily selective antibiotic agrocin 84, and simplified structural component analogues

Alternative syntheses of 9-(3-deoxy-β-D-threo-pentofuranosyl)adenine ( 4 ), the core nucleoside of agrocin 84 [and its 2′-deoxy threo isomer 5 ] were devised: (1) direct conversion of 9-(β-D-arabinofuranosyl)adenine into 9-(2,3-anhydro-β-D-lyxofuranosyl)adenine and regioselective opening of its oxirane ring with sodium borohy-dride to give 4 and 5 (?7.5:1); (2) treatment of adenosine with sodium hydride and 2,4,6-triisopropylbenzene-sulfonyl chloride, and subjection of the resulting 2′(3′)-sulfonates to the reductive [1,2]-hydride shift rearrangement with lithium triethylborohydride to give 4 and 5 (? 2:1); and (3) subjection of the phenoxythiocar-bonyl esters of 9-[2(3),5-bis-O-(tert-butyldimethylsilyl)-β-D-arabinofuranosyl]adenine to Barton deoxygenation, and deprotection to give 4 and 2′-deoxyadenosine (?5:1). Methods (2) and (3) gave lower yields. Syntheses of simplified 6-N- and 5′-O-adenosine phosphoramidate model compounds were explored to examine potential access to such features in the structure proposed for agrocin 84.     

9-deazapurine nucleosides. The synthesis of certain N-5-2′-deoxy-β-D-erythropentofuranosyl and N-5-β-D-arabinofuranosylpyrrolo[3,2-d]pyrimidines

A number of 2,4-disubstituted pyrrolo[3,2-d]pyrimidine N-5 nucleosides were prepared by the direct glycosylation of the sodium salt of 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine (3) using 1-chloro-2-deoxy-3,5-di-O-(p-toluoyl)-α-D -erythropentofuranose (1) and 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose (11) . The resulting N-5 glycosides, 2,4-dichloro-5-(2-deoxy-3,5-di-O-(p-toluoyl) -β-D-erythropentofuranosyl)-5H-pyrrolo-[3,2-d]pyrimidine (4) and 2,4-dichloro-5-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl-5H -pyrrolo [3,2-d)pyrimidine (12) , served as versatile key intermediates from which the N-7 glycosyl analogs of the naturally occurring purine nucleosides adenosine, inosine and guanosine were synthesized. Thus, treatment of 4 with methanolic ammonia followed by dehalogenation provided the adenosine analog, 4-amino-5-(2-deoxyerythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidine (6) . Reaction of 4 with sodium hydroxide followed by dehalogenation afforded the inosine analog, 5-(2-deoxy-β-D-erythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (9) . Treatment of 4 with sodium hydroxide followed by methanolic ammonia gave the guanosine analog, 2-amino-5-(2-deoxy-β-D-erythropentofuranosyl) -5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one (10) . The preparation of the same analogs in the β-D-arabinonucleoside series was achieved by the same general procedures as those employed for the corresponding 2′-deoxy-β-D-ribonucleoside analogs except that, in all but one case, debenzylation of the sugar protecting groups was accomplished with cyclohexene-palladium hydroxide on carbon, providing 4-amino-5-β-D-arabinofuranosyl-5H-pyrrolo [3,2-d]pyrimidin-4(3H)-one (18) . Structural characterization of the 2′-deoxyribonucleoside analogs was based on uv and proton nmr while that of the arabinonucleosides was confirmed by single-crystal X-ray analysis of 15a . The stereospecific attachment of the 2-deoxy-β-D-ribofuranosyl and β-D-arabinofuranosyl moieties appears to be due to a Walden inversion at the C₁ carbon by the anionic heterocyclic nitrogen (S_N2 mechanism).     

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes

ABSTRACT

The four derivatives of β-maltosyl-(1→4)-trehalose have been synthesized, which are monodeoxygenated at the site of one of the primary hydroxyl groups. The tetrasaccharides were constructed in [2+2] block syntheses. Thus, 6′″-deoxy-β-maltosyl-(1→4)-trehalose was prepared by selective iodination of allyl 2,3,6,2′,3′-penta-O-acetyl-β-maltoside (3) followed by catalytic hydrogenolysis and coupling with 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (9), and 6″-deoxy-β-maltosyl-(1→4)-trehalose by selective iodination of allyl 4′,6′-O-isopropylidene-β-maltoside (14), coupling with 9, and one-step hydrogenolysis at the tetrasaccharide level. For the synthesis of 6′-deoxy-β-maltosyl-(1→4)-trehalose, the diol 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′-di-O-benzyl-α-D-glucopyranoside (22) was selectively iodinated and glycosylated with acetobromomaltose followed by catalytic hydrogenolysis. The 6-deoxy-β-maltosyl-(1→4)-trehalose was obtained upon selective iodination of a tetrasaccharide diol.     

Synthesis of Certain 5-Substituted 2′-Deoxytubercidin Derivatives

The synthesis of the 7-deaza-2′-deoxy-adenine derivatives 7b–3 with chloro, bromo, or methyl substituents at C(5) is described. Glycosylation of the 5-substituted 4-chloropyrrolo[2,3-d]pyrimidines 4b–d with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 3 ) gave the β-D -nucleosides 5b–d , exclusively. They were deblocked (→ 6b–d ) and converted into the tubercidin derivatives 7b–d .     

Synthesis of Methyl 2-Acetamido-4,6-di-O-acetyl-3-S-acetyl-2-deoxy-3-thio-α-D-mannopyranoside

Methyl-2-acetamido-4,6-di-O-acetyl-3-S-acetyl-2-deoxy-3-thio-α-D-mannopy-ranoside has been synthesized by conversion of methyl 2-amino-2-deoxy-4,6-O-benzylidene-α-D-altropyranoside into the corresponding 3-O-methanesulfony1-2-N-[(methylthio)thiocarbonyl]derivative followed by intramolecular displacement of the 3-O-methanesulfonyloxy group with the (methylthio)thiocarbamoyl group.     

Synthesis of the Methyl Glycosides of a Di- and Two Trisaccharide Fragments Specific for the Shigella flexneri Serotype 2a O-Antigen

ABSTRACT

The stereocontrolled synthesis of methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (EC, 1), methyl α-L-rhamnopyranosyl-(1→3)-[α-D-glucopyranosyl-(1→4)]-α-L-rhamnopyranoside (B(E)C, 3) and methyl α-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polysaccharide of Shigella flexneri serotype 2a. Emphasis was put on the construction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl fluoride (8) as the donor. Condensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyl-α-L-rhamnopyranoside (11) and 8 afforded the fully protected αE-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding βE-anomer 21. Deacetalation and regioselective benzoylation of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25. Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively. The corresponding βE-disaccharide, namely, methyl β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranoside (βEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the coupling of a precursor to residue E and a disaccharide CD. Route 2 was based on the condensation of an appropriate EC donor and a precursor to residue D. The former route afforded a 1:2 mixture of the αE and βE condensation products which could not be separated, neither at this stage, nor after deacetalation. In route 2, the required αE-anomer was isolated at the disaccharide stage and transformed into 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl-(1→4)-2,3-di-O-benzoyl-α-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyran-oside (19) was preferred to its benzylidene analogue as the precursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.     

Synthesis Of Ligands Related To The O-Specific Antigen Of Shigella Dysenteriae Type 1.

Abstract

Stereoselective α-D-galactosylation at the position 3 of 4,6-O-substituted derivatives of methyl 2-acetamido-2-deoxy-α-D-glucopyranoside is described. Glycosyl chlorides derived from 3,4,6-tri-O-acetyl-2-O-benzyl- and 2-O-(4-methoxybenzyl)-D-galactopyranose have been used as glycosyl donors. Methyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (27) and methyl 2-acetamido-4,6-di-O-benzyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (31) have been prepared.     

7-Halogenated 7-Deaza-2′-deoxyinosines

The synthesis of the 7-deaza-2′-deoxyinosine derivatives 3a – c with chloro, bromo, and iodo substituents at position 7 is described. Glycosylation of the 7-halogenated 6-chloro-7-deazapurines 4a – c or of the 7-halogenated 6-chloro-7-deaza-2-(methylthio)purines 9a – c with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 5 ) furnished the intermediates 7a – c and 11a – c , respectively, which gave, upon deprotection, the desired nucleosides 3a – c .     

Ring Opening of Benzyl β-D-Galactoside Cyclic Sulfates into Galactose Monosulfates. New Access to 6-Deoxy-Galacto-Hex-5-Enopyranoside and 4-Deoxy-3-Ketogalactopyranoside.

ABSTRACT

The behavior of 3,4- and 4,6-cyclic sulfates derived from benzyl 2,6- and 2,3-di-O-benzyl-β-D-galactopyranosides toward hydrolysis has been studied using aqueous sodium hydroxide under various conditions. Starting from benzyl 2,6-di-O-benzyl-3,4-O-sulfuryl-β-D-galactopyranoside (5), the reaction with aq NaOH in THF gave both 3- and 4-monosulfates 7 and 8 (83%, in 68:32 ratio), while the reaction in DMF led unexpectedly to the 4-deoxy-3-keto derivative 10 in 77% yield after acidic hydrolysis of the intermediate enolester 9. On the other hand, when benzyl 2,3-di-O-benzyl-4,6-O-sulfuryl-β-D-galactopyranoside (6) was treated with aq NaOH in THF, a mixture of benzyl 2,3-di-O-benzyl-6-deoxy-4-O-(sodium sulfonato)-α-L-arabino-hex-5-enopyranoside (11) and benzyl 2,3-di-O-benzyl-4-deoxy-6-O-(sodium sulfonato)-α-L-threo-hex-4-enopyranoside (12) (in 65:35 ratio) was obtained in 93% yield, giving a new and rapid access to 11, a potential precursor of L-sugars derivatives. Alternatively, BzONBu₄ gave a regiospecific opening reaction of 6 and led to the 6-O-benzoate 4-O-sulfate derivative (13) in excellent yield.     

A facile and improved synthesis of tubercidin and certain related pyrrolo[2,3-d]pyrimidine nucleosides by the stereospecific sodium salt glycosylation procedure

A simple synthesis of tubercidin ( 1 ), 7-deazaguanosine ( 2 ) and 2′-deoxy-7-deazaguanosine ( 14 ) has been accomplished using the sodium salt glycosylation procedure. Reaction of the sodium salt of 4-chloro- and 2-amino-4-chloro-pyrrolo[2,3-d]pyrimidine, 3 and 4 , respectively, with 1-chloro-2,3-0-isopropylidene-5-0-(t-butyl)dimethylsilyl-α-D-ribofuranose ( 5 ) gave the corresponding protected nucleosides 6n and 7 with β-anomeric configuration. Deprotection of 6 provided 8 , which on heating with methanolic ammonia gave tubercidin ( 1 ) in excellent yield. Functional group transformation of 7 , followed by deisopropylidenation gave 2-aminotubercidin ( 10 ) and 2-amino-7-β-D-ribofuranosylpyrrolo[2,3-d]pyrimidine-4(3H)-thione ( 11 ). Treatment of 7 with 1N sodium methoxide followed by exposure to aqueous trifluoroacetic acid, and ether cleavage furnished 7-deazaguanosine ( 2 ). 2′-Deoxy-7-deazaguanosine ( 14 ) and 2′-deoxy-7-deaza-6-thioguano-sine ( 18 ) were also prepared by using similar sequence of reactions employing 4 and 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose ( 15 ).     

Synthetic Studies on Sialoglycoconjugates 75: A Total Synthesis of β-Series Ganglioside GQ1β

Abstract

A first total synthesis of a β-series ganglioside GQ1β (IV³Neu5Acα2, III⁶Neu5Acα2-Gg4Cer) is described. Regio- and stereoselective dimeric sialylation of the hydroxyl group at C-6 of the GalNAc residue in 2-(trimethylsilyl)ethyl O-(2-acetamido-2-deoxy-3-O-levulinyl-β-d-galactopyranosyl)-(1→4)-O-(2,3,6-tri-O-benzyl-β-d-galactopyranosyl)-(1→4)-O-2,3,6-tri-O-benzyl-β-d-glucopyranoside (3) with methyl [phenyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-2-thio-d-glycero-d-galacto-2-nonulopyranosid]onate (4) using N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) as a promoter gave the desired pentasaccharide 5 containing α-glycosidically-linked dimeric sialic acids. This was transformed into the acceptor 6 by removal of the levulinyl group. Condensation of methyl O-[methyl 5-acetamido-8-O-(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-d-glycero-α-d-galacto-2-nonulopyranosylono-1′,9-lactone)-4,7-di-O-acetyl-3,5-dideoxy-d-glycero-d-galacto-2-nonulopyranosylonate]-(2→3)-2,4,6-tri-O-benzoyl-1-thio-β-d-galactopyranoside (7) with 6, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the desired octasaccharide derivative 8 in high yield. Compound 8 was converted into α-trichloroacetimidate 11, via reductive removal of the benzyl groups, O-acetylation, removal of the 2-(trimethylsilyl)ethyl group, and treatment with trichloroacetonitrile, which, on coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (12), gave the β-glycoside 13. Finally, 13 was transformed, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into the title ganglioside 15 in good yield.     

Synthesis of per-6-guanidinylated cyclodextrins

Reaction of per(6-amino-6-deoxy-2,3-di-O-methyl)-α-, β- and γ-cyclodextrins with N,N′-bis(tert-butoxycarbonyl)-N″-triflylguanidine and triethylamine in tetrahydrofuran gave per[6-N,N′-bis(tert-butoxycarbonyl)guanidino-6-deoxy-2,3-di-O-methyl]-α-, β- and γ-cyclodextrins, respectively. Subsequent cleavage of the protective groups with trifluoroacetic acid in dichloromethane afforded per(6-deoxy-6-guanidino-2,3-di-O-methyl)-α-, β- and γ-cyclodextrins in very good overall yields.     

Enzymic Hydrolysis of Methyl 2,3-O-Acetyl-5-Deoxy-α and β-D-Xylofuranosides - An Active-Site Model of Pig Liver Esterase

Abstract

The regioselective enzymic hydrolysis of methyl 2,3-di-O-acetyl-5-deoxy-α-D-xylofuranoside (1) and methyl 2,3-di-O-acetyl-5-deoxy-β-D-xylofuranoside (2) in the presence of pig liver esterase (PLE) was studied by GLC. Diacetate 2 gave exclusively methyl 3-O-acetyl-5-deoxy-β-D-xylofuranoside (6) while diacetate 1 produced both methyl 2-O-acetyl-5-deoxy-α-D-xylofuranoside (3) and methyl 3-O-acetyl-5-deoxy-α-D- xylofuranoside (4) in low yield. At high conversion, methyl 5-deoxy-α-D-xylofuranoside (7) was the only product. The first-order rate constants, Michaelis constants, and maximal velocities were determined for 1, 2, and the monoacetates 3 - 6. The results were interpreted on the basis of a recent active-site model for PLE.     

Sulfated 1, 6-AnhydrO-4-O-(β-D-Glucopyranosyluronate)-β-D-Glucopyranosyl Derivatives: Syntheses And Conformations

Abstract

A series of sulfated 1,6-anhydro-4-O-(β-D-glucopyranosyluronate)-β-D-glucopyranose derivatives 7 and 9-13 with different degrees of charge was synthesized from a common disaccharide precursor 1,6-anhydro-2-azido-2-deoxy-4-O-(methyl2,3-di-O-benzyl-β-D-glucopyransyl-uronate-β-D-glucopyranose (5). For the 1,6-anhydro-β-D-glucopyranose moiety of this compound a boat-chair equilibrium is found, the boat conformation being stabilized by an intramolecular hydrogen bridge. The fully sulfated β-D-glucopyranosyl-uronates 10 and 13 occur in unusual nonchair conformations.     

Stereoselective synthesis of pyrrolo[2,3-d]pyrimidine α- and β-D-ribonucleosides from anomerically pure D-ribofuranosyl chlorides: Solid-Liquid Phase-Transfer Glycosylation and 15N-NMR Spectra

Solid-liquid phase-transfer glycosylation (KOH, tris[2-(2-methoxyethoxy)ethye]amine ( = TDA-1), MeCN) of pyrrolo[2,3-d]pyrimidines such as 3a and 3b with an equimolar amount of 5-O-[(1,1 -dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribofuranosyl chloride (1) [6] gave the protected β-D -nucleosides 4a and 4b , respectively, stereoselectively (Scheme). The β-D -anomer 2 [6] yielded the corresponding α-D -nucleosides 5a and 5b with traces of the β-D -compounds. The 6-substituted 7-deazapurine nucleosides 6a , 7a , and 8 were converted into tubercidin (10) or its α-D -anomer (11) . Spin-lattice relaxation measurements of anomeric ribonucleosides revealed that T₁ values of H? C(8) in the α-D -series are significantly increased compared to H? C(8) in the β-D -series while the opposite is true for T₁ of H? C(1′). ¹⁵N-NMR data of 6-substituted 7-deazapurine D -ribofuranosides were assigned and compared with those of 2′-deoxy compounds. Furthermore, it was shown that 7-deaza-2′deoxyadenosine ( = 2′-deoxytubercidin; 12 ) is protonated at N(1), whereas the protonation site of 7-deaza-2′-deoxyguanosine ( 20 ) is N(3).     

Syntheses,molecular structures,and antiviral activities of 1- and 2-(2′-deoxy-d-ribofuranosyl)cyclohepta[d][1,2,3]triazol-6(1H)-ones and 1-(2′-deoxy-d-ribofuranosyl)cyclohepta[b]pyrrol-8(1H)-one

The synthesis of a novel class of 2′-deoxyribonucleosides possessing tropone-fused nitrogen heterocycles as nucleobases was developed. The reaction of alkali metal salts of 1H-cyclohepta[d][1,2,3]triazol-6-one with 2-deoxy-3,5-di-O-(p-toluoyl)-α-d-ribofuranosyl chloride (α-chlorosugar) afforded an anomeric mixture of N1- and N2-coupled glycosylation products. Good stereospecificity in relation to the amount of the β-anomer was achieved in the less polar solvent DME. The reactions of the sodium salt of 1H-cyclohepta[b]pyrrol-8-one and its 3-methyl derivative with an α-chlorosugar in DME gave the β-anomer of the N1-coupled glycosylation products. The glycosylation products were treated with NaOMe in MeOH to produce the desired 2′-deoxyribonucleosides. X-ray structural analyses of the three nucleosides prepared confirmed their anomeric configuration and revealed that their sugars were puckered. The β-anomers of the nucleosides had weak antiviral activities for herpes simplex virus type 1 and herpes simplex virus type 2 in comparison with those of acyclovir (ACV). These nucleosides showed no cytotoxicity on a lung (A549) and two colon (HT-29 and HCT-116) cancer cell lines.