Arabino Derivatives Research Articles

Domino reactions of 5-deoxy-5-iodo- d- xylo- and - l-arabinofuranose derivatives with organometallic reagents. A way towards polyfunctionalized building-blocks

Domino reactions involving metal–halogen exchange, furanose ring-opening and nucleophilic addition from 3- O-benzyl-5-deoxy-5-iodo-1,2- O-isopropylidene-α- d-xylofuranose and the epimeric l- arabino derivative with various organometallic reagents are reported. In anhydrous conditions, with a large excess of organolithium or Grignard reagents, vicinal diols are obtained with good yields and a fair diastereoselectivity. Interestingly, with α-trimethylsilyl organolithium reagents, the fragmentation of the furanose ring to the substituted pent-4-enal is followed by a Peterson olefination giving dienic compounds in a four-step one-pot process.

Synthesis of (-)-neplanocin A analogues as potential antiviral agents.

Based on (-)-neplanocin A with the 5'-hydroxyl substituted with fluoro, azido, or amino group, the corresponding xylo- and arabino derivatives were synthesized from D-ribose using the Mitsunobu reaction as a key step. None of the final nucleosides did show either significant antiviral activities or cytotoxicities.

Synthesis and enzymatic evaluation of modified acceptors of recombinant blood group A and B glycosyltransferases

The disaccharide α- l-Fuc p-(1→2)-β- d-Gal p-(1→ O)-Octyl ( 1) is an acceptor for the human blood group A and B glycosyltransferases. Seven analogues of 1, containing deoxy, methoxy and arabino modifications of the Fuc residue, were chemically synthesized and kinetically evaluated in radioactive enzymatic assays. Both the enzymes tolerate modification of the 3′-OH on the fucose residue. The 2′-OH was found to be key to the recognition of the acceptors by these enzymes. The arabino derivative was recognized as an acceptor by the A transferase ( K m of 200 μM), but not the B transferase and is the first synthetic acceptor capable of distinguishing between the two enzyme activities.

A Convenient Synthesis of N4,O3′, O5′-Triacetyl-2′-Ketocytidine

A convenient synthesis of the title compound in four steps from cytidine is reported. Key transformations include differentiation of the 2′ position as N4,O3′,O5′-triacetyl-2,2′-anhydrocytidine, opening to the arabino derivative, and oxidation of the 2′ position with the Dess-Martin reagent.

The Mechanism of Inhibition of S-Adenosyl-L-Homocysteine Hydrolase by Fluorine-Containing Adenosine Analogs

(Z)-4',5'-Didehydro-5'-deoxy-5'-fluoroadenosine (I), 5'-deoxy-5'-difluoroadenosine (II), and 4',5'-didehydro-5'-deoxy-5'-fluoroarabinosyl-adenosine (III) are inhibitors of rat liver S-adenosyl-L-homocysteine hydrolase. Compounds I and II are time-dependent and irreversible inhibitors of the enzyme. Both I and II are oxidized by E.NAD to produce E.NADH, and fluoride anion is formed in the inactivation reaction (0.7 to 1.0 mole fluoride/mole of enzyme subunit, and 1.7 moles fluoride/mole of enzyme subunit from I and II, respectively). The enzyme is stoichiometrically labeled with [8-3H]-I, but the label is lost upon denaturation of the protein either with or without treatment of the labeled complex with sodium borohydride. The compound III, the arabino derivative of I, is a competitive inhibitor of the enzyme. The mechanism of the inhibition of S-adenosyl-L-homocysteine hydrolase by these inhibitors is discussed.

Desulfonyloxylations of some secondary p-toluenesulfonates of glycosides by lithium triethylborohydride; a high-yielding route to 2- and 3-deoxy sugars

Lithium triethylborohydride (LTBH) reacts readily with p-toluenesulfonates of methyl 4,6- O-benzylidene-α- d-glucopyranoside ( 4) to give deoxyglycosides in > 90% yield. Thus, the 2,3-ditosylate ( 1) and the 3-monotosylate ( 2) thereof afford methyl 4,6- O-benzylidene-2-deoxy-α- d- ribo-hexopyranoside ( 7) in highly regio- and stereo-selective reactions that proceed via methyl 2,3-anhydro-4,6- O-benzylidene-α- d-allopyranoside ( 6), and the 2-monotosylate ( 8) of 4 gives the 3-deoxy-α- d- arabino isomer ( 12) of 7 via the corresponding 2,3-anhydro-α- d-mannopyranoside 11. In the series of the corresponding β anomers, the 3-monotosylate 14 and the 2-monotosylate 16 are similarly desulfonyloxylated, with equal ease, but furnish mixtures of regioisomeric deoxyglycosides, namely, the 3- and 2-deoxy-β- d- ribo derivatives 20 and 21, and 2- and 3-deoxy-β- d- arabino derivatives 22 and 23, respectively. It could be shown that this difference is due to the failure of the intermediary, β-glycosidic epoxides 18 and 19 (the anomers of 6 and 11) to obey the Fürst-Plattner rule in their reductive ring-opening with LTBH. The β-glycosidic 2,3-ditosylate 15 reacts less readily, and gives 20–23, with 20 preponderating. The 2-O-methyl-3- O-tosyl-β- d-glucopyranoside 24 is partly desulfonylated and partly desulfonyloxylated, whereas its 3- O-methyl-2- O-tosyl isomer 27 undergoes desulfonylation exclusively. The reductions of 1, 2, and 8 by LTBH are compared with those previously effected by lithium aluminum hydride, which are slower, involve considerable desulfonylation, and afford lower yields of deoxyglycosides, with the main products differing from those obtained by the action of LTBH. Mechanistic differences associated with the two reductants are discussed.

Synthesis and stereochemical characterization of a series of five-carbon, acyclic-sugar derivatives of 1,6-dihydro-6-thioxopurine (6-mercaptopurine)

The four acetylated d-aldose diethyl dithioacetals ( 1a-d) were treated with bromine to give the corresponding, unstable 1-bromides ( 2a-d), which were immediately condensed with 6-chloro-9-(chloromercuri)purine ( 3) to furnish the respective, protected nucleosides ( 4a-d). Subsequent treatment with thiourea gave the crystalline 6-mercaptopurine analogs ( 5a-d) which, upon deacetylation in butylamine-tetrahydrofuran, gave the free, acyclic-sugar nucleosides ( 6a-d)- With the exception of the arabino derivative 4b, the 6-chloropurine derivatives were mixtures of 1′-epimers. Crystallization of the acylated 6-mercaptopurine derivatives afforded single 1′-epimers for 5a-c; 5d remained an epimeric mixture. A positive Cotton effect for both the ribo and arabino analogs 5a and 5b, and a negative Cotton effect for the xylo derivative 5c, suggested the (1′ R) configuration for 5a and 5b, and the (1′ S) configuration for 5c. Proof of the stereochemistry at C-1 (as well as proof of derivatization at N-9 of the purine ring) was afforded by X-ray crystallographic analysis of the arabino derivative 5b, which was demonstrated to have the (1′ R) configuration. Use of the Generalized Heterocycle Rule also supported the stereochemical attributions at C-1′ for the remaining compounds. The arabino derivative 5b adopts an extended, planar, zigzag conformation of the side chain in solution, as well as in the crystalline state, whereas the ribo ( 5a) and xylo ( 5c) derivatives exist in solution as non-extended, sickle conformations; the lyxo analog ( 5a) was found to be a mixture of 1′-epimers, both of which adopt in solution an extended, planar, zigzag arrangement of the sugar chain.

Conformation of acyclic derivatives of sugars Part VIII. Conformations of the 2,3,4,5-tetra- O-acetylpentose dimethyl acetals in solution

The conformations of the peracetylated aldopentose dimethyl acetals having the d- ribo ( 1), l- arabino ( 2), d- xylo ( 3), and d- lyxo ( 4) configurations have been studied in chloroform- d solution by n.m.r. spectroscopy at 100 and 220 MHz. The arabino derivative 2 adopts a planar, zigzag conformation almost exclusively, whereas the other three examples adopt conformations in which parallel 1,3-interactions between substituents, that would be present in the extended forms, are relieved. In the lyxo derivative 4, rotation about C-1—C-2 from the extended form is involved. The ribo derivative 1 tends to adopt a sickle conformation through rotation about C-2—C-3 to bring C-1 out of the approximate plane of the other atoms in the chain; the xylo derivative behaves similarly, but with rotation about C-3—C-4 to bring C-5 out of the plane. The derivatives 1–4 exhibit mass-spectral fragmentation pathways very similar to those of the peracetylated aldose diethyl dithioacetals.

Conformational studies on pyranoid sugar derivatives by n.m.r. spectroscopy. Conformational equilibria of the peracetylated and some perbenzoylated methyl d-aldopentopyranosides in solution

The method of averaging of spin-coupling was used to determine by n.m.r. spectroscopy the conformational populations of the eight methyl d-aldopentopyranoside triacetates and the corresponding tribenzoates having the β- d- ribo, β- d- arabino, α- d- xylo, β- d- xylo, and α- d- lyxo configurations. The α- d- xylo derivatives adopt the C1( d) conformation almost exclusively, and the β- d- arabino derivatives favor the 1C( d) conformation very strongly; in solution, the other examples have substantial proportions of both chair conformers. The axial-directing effect of the methoxyl group at C-1 is greater than that of the acetoxy or benzoyloxy group, except when the axial 1-substituent would be syn-axial to the 3-substituent. The axial-directing effect of the methoxyl group at C-1 is enhanced by replacing acetoxy groups at C-2, 3, and 4 by benzoyloxy groups. The axial-directing effect of a 1-substituent is discussed in terms of polar and steric contributions. For methyl 2,3,4-tri- O-benzoyl-β- d-xylopyranoside, the proportion of the all-axial chair conformer was found to decrease with increasing polarity of the solvent; this behavior contrasts with that observed with some aldopentopyranose tetraacetates and tri- O-acetyl-β- d-xylopyranosyl chloride, for which the polarity of the solvent has little effect on conformational populations.

Diphenyl dithioacetals of d-ribose, d-xylose, and d- and l-arabinose. Conformational studies and formation of a ketene diphenyl dithioacetal

d-Ribose, d-xylose, d-arabinose, and l-arabinose have been converted in good yield into their respective diphenyl dithoacetals, 1, 5, 8, and 3. The tetraacetate 4 of 3 adopts a planar, zigzag conformation in chloroform solution, but the d- xylo analog 6 and d- ribo analog 2 adopt conformations that have no parallel 1,3-interactions of acetoxyl groups. A crystalline diisopropylidene acetal 7 was obtained from 1. On treatment with a strong base, the corresponding acetal 9 from the d- arabino derivative 8 underwent elimination of acetone to give the ketene diphenyl dithioacetal 10, characterized as its crytalline 3- p-nitrobenzoate 11 and its remarkably stable 3-methyl ether 12.