Solution Structure of a RNA Decamer Duplex,Containing 9‐[2‐O‐(β‐D‐ribofuranosyl)‐β‐D‐ribofuranosyl]adenine,a Special Residue in Lower Eukaryotic Initiator tRNAs

The solution structure of the self‐complementary deca‐ribonucleotide 5′‐r(GCGA*AUUCGC)‐3′ containing 9‐[2‐O‐(β‐D ‐ribofuranosyl)‐β‐D ‐ribofuranosyl]adenine (A*), a modified nucleotide that occurs in lower eukaryotic methionine initiator tRNAs (tRNAs_i^Met), was determined by NMR spectroscopy. Unexpectedly, the modification has no effect on the thermal stability of the duplex. However, the extra ribose moiety is in the C(3′)‐endo conformation and takes up a well‐defined position in the minor groove, which is in agreement with its position in tRNAs_i^Met as determined by X‐ray crystallography. Molecular‐dynamics simulations on the RNA duplex in H₂O show that the position of the extra ribofuranose moiety seems to be stabilized by bridged H‐bonds (mediated by two H₂O molecules) to the backbone of the complementary chain.     

Synthesis and Conformational Analysis of 1′‐ and 3′‐Substituted 2‐Deoxy‐2‐fluoro‐D‐ribofuranosyl Nucleosides

Convergent syntheses of the 9‐(3‐X‐2,3‐dideoxy‐2‐fluoro‐β‐D ‐ribofuranosyl)adenines 5 (X=N₃) and 7 (X=NH₂), as well as of their respective α‐anomers 6 and 8 , are described, using methyl 2‐azido‐5‐O‐benzoyl‐2,3‐dideoxy‐2‐fluoro‐β‐D ‐ribofuranoside ( 4 ) as glycosylating agent. Methyl 5‐O‐benzoyl‐2,3‐dideoxy‐2,3‐difluoro‐β‐D ‐ribofuranoside ( 12 ) was prepared starting from two precursors, and coupled with silylated N⁶‐benzoyladenine to afford, after deprotection, 2′,3′‐dideoxy‐2′,3′‐difluoroadenosine ( 13 ). Condensation of 1‐O‐acetyl‐3,5‐di‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐β‐D ‐ribofuranose ( 14 ) with silylated N²‐palmitoylguanine gave, after chromatographic separation and deacylation, the N⁷‐β‐anomer 17 as the main product, along with 2′‐deoxy‐2′‐fluoroguanosine ( 15 ) and its N⁹‐α‐anomer 16 in a ratio of ca. 42 : 24 : 10. An in‐depth conformational analysis of a number of 2,3‐dideoxy‐2‐fluoro‐3‐X‐D ‐ribofuranosides (X=F, N₃, NH₂, H) as well as of purine and pyrimidine 2‐deoxy‐2‐fluoro‐D ‐ribofuranosyl nucleosides was performed using the PSEUROT (version 6.3) software in combination with NMR studies.     

Flavonol Glycosides with α‐Glucosidase Inhibitory Activities and New Flavone C‐Diosides from the Leaves of Machilus konishii

Seventeen flavonoids, five of which are flavone C‐diosides, 1 – 5 , were isolated from the BuOH‐ and AcOEt‐soluble fractions of the leaf extract of Machilus konishii. Among 1 – 5 , apigenin 6‐C‐β‐D ‐xylopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 2 ), apigenin 8‐C‐α‐L ‐arabinopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 4 ), and apigenin 8‐C‐β‐D ‐xylopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 5 ) are new. Both 4 and 5 are present as rotamer pairs. The structures of the new compounds were elucidated on the basis of NMR‐spectroscopic analyses and MS data. In addition, the ¹H‐ and ¹³C‐NMR data of apigenin 6‐C‐α‐L ‐arabinopyranosyl‐2″‐O‐β‐D ‐glucopyranoside ( 3 ) were assigned for the first time. The isolated compounds were assayed against α‐glucosidase (type IV from Bacillus stearothermophilus). Kaempferol 3‐O‐(2‐β‐D ‐apiofuranosyl)‐α‐L ‐rhamnopyranoside ( 12 ) was found to possess the best inhibitory activity with an IC₅₀ value of 29.3 μM .     

Synthesis of 5′‐O‐(2‐Azido‐2‐deoxy‐α‐D‐glycosyl)nucleosides and Their Antitumor Activities

The 1,3,4,6‐tetra‐O‐acetyl‐2‐azido‐2‐deoxy‐β‐D ‐mannopyranose ( 4 ) or the mixture of 1,3,6‐tri‐O‐acetyl‐2‐azido‐2‐deoxy‐4‐O‐(2,3,4,6‐tetra‐O‐acetyl‐β‐D ‐galactopyranosyl)‐β‐D ‐mannopyranose ( 10 ) and the corresponding α‐D ‐glucopyranose‐type glycosyl donor 9 / 10 reacted at room temperature with protected nucleosides 12 – 15 in CH₂Cl₂ solution in the presence of BF₃?OEt₂ as promoter to give 5′‐O‐(2‐azido‐2‐deoxy‐α‐D ‐glycosyl)nucleosides in reasonable yields (Schemes 2 and 3). Only the 5′‐O‐(α‐D ‐mannopyranosyl)nucleosides were obtained. Compounds 21, 28, 30 , and 31 showed growth inhibition of HeLa cells and hepatoma Bel‐7402 cells at a concentration of 10 μM in vitro.     

Synthesis of 2‐(sulfamoylphenyl)‐4′‐(iminoaryl/hetroaryl)‐4‐(4′′‐hydroxyphenyl)‐thiazoles and their O‐glucosides

In continuation of our work, we synthesized 2‐(sulfamoylphenyl)‐4′‐amino‐4‐(4″‐hydroxyphenyl)‐thiazole ( 3a ), which were reacted with various (aryl/hetroaryl) aldehyde to form 2‐(sulfamoylphenyl)‐4′‐(iminoaryl/hetroaryl)‐4‐(4″‐hydroxyphenyl)‐thiazoles ( 4a , 4b , 4c , 4d , 4e , 4f ). Glucosylation of compounds ( 4a , 4b , 4c , 4d , 4e , 4f ) have been done by using acetobromoglucose as a glucosyl donor to afford 2‐(sulfamoylphenyl)‐4′‐(iminoaryl/hetroaryl)‐4‐(2,3,4,6‐tetra‐O‐acetyl‐4″‐O‐β‐D ‐glucosidoxyphenyl)‐thiazoles ( 5a , 5b , 5c , 5d , 5e , 5f ), further on deacetylation to produce 2‐(sulfamoylphenyl)‐4′‐(iminoaryl/hetroaryl)‐4‐(4″‐O‐β‐D ‐glucosidoxyphenyl)‐thiazoles ( 6a , 6b , 6c , 6d , 6e , 6f ). The compounds are confirmed by FTIR, ¹H‐NMR, ¹³C‐NMR, and ES‐Mass spectral analysis. J. Heterocyclic Chem., (2011).     

Synthesis of [2′‐2H1]‐Ribonucleosides

New syntheses of C(2′)‐deuterated ribonucleosides have been accomplished starting either from 3,5‐di‐O‐benzyl‐1‐O‐methyl‐α,β‐D ‐ribofuranose ( 1b ) or 2,3‐O‐isopropylidene‐D ‐ribose ( 14 ), with >97 atom‐% D incorporation in both cases. The former is suited to the demands of multiple‐site deuteration or uniform ¹³C/multiple ²H double labeling of the ribofuranose moiety, whereas the latter is particularly appropriate for single‐site ²H labeling for mechanistic studies of enzyme reactions.     

Metal‐Ion‐Binding Analogs of Ribonucleosides: Preparation and Formation of Ternary Pd2+ and Hg2+ Complexes with Natural Pyrimidine Nucleosides

Four metal‐ion‐binding nucleosides, viz. 2,6‐bis(1‐methylhydrazinyl)‐9‐(β‐D ‐ribofuranosyl)‐9H‐purine ( 2a ) and its N‐acetylated derivative, 2b , 2,4‐bis(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐5‐(β‐D ‐ribofuranosyl)pyrimidine ( 3 ), and 2,4‐bis(1‐methylhydrazinyl)‐5‐(β‐D ‐ribofuranosyl)pyrimidine ( 4 ) have been synthesized. The ability of these nucleosides and the previously prepared 2,6‐bis(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐9‐(β‐D ‐ribofuranosyl)‐9H‐purine to form Pd²⁺‐ and Hg²⁺‐mediated complexes with uridine has been studied by ¹H‐NMR spectroscopy. To obtain additional support for the interpretation of the NMR data, comparative measurements on the ternary‐complex formation between pyridine‐2,6‐dicarboxamide ( 5 ), pyrimidine nucleosides, and K₂PdCl₄ were carried out.     

Cationic ring‐opening polymerization of 1,6‐anhydro‐2,3,4‐tri‐O‐allyl‐β‐D‐glucopyranose as a convenient synthesis of dextran

For the convenient synthesis of (1→6)‐α‐D ‐glucopyranan, i. e., dextran ( 4 ), ring‐opening polymerization of 1,6‐anhydro‐2,3,4‐tri‐O‐allyl‐β‐D ‐glucopyranose ( 1 ) has been carried out using BF₃·OEt₂. With a ratio of [BF₃·OEt₂]/[ 1 ] = 0.5 at 0 °C for 140 h, the yield and M_n of the obtained polymer are 84.0% and 21 700, respectively. The polymer consists of (1→6)‐α‐linked 2,3,4‐tri‐O‐allyl‐D ‐glucopyranose ( 2 ) which is similar to the results for the cationic ring‐opening polymerization of 1,6‐anhydro‐2,3,4‐tri‐O‐methyl‐β‐D ‐glucopyranose and 1,6‐anhydro‐2,3,4‐tri‐O‐ethyl‐β‐D ‐glucopyranose. Polymer 2 was isomerized using tris(triphenylphosphine)‐chlororhodium as the catalyst in toluene/ethanol/water to yield polymeric 2,3,4‐tri‐O‐propenyl‐(1→6)‐α‐D ‐glucopyranan ( 3 ). Deprotection of the propenyl ether linkage of 3 was then performed using hydrochloric acid in acetone to give 4 .     

Pentopyranosyl Oligonucleotide Systems,Communication No.12, The β‐D‐Xylopyranosyl‐(4′→2′‐oligonucleotide System

β‐D ‐Xylopyranosyl‐(4′→2′)‐oligonucleotides containing adenine and thymine as nucleobases were synthesized as a part of a systematic study of the pairing properties of pentopyranosyl oligonucleotides. Contrary to earlier expectations based on qualitative conformational criteria, β‐D ‐xylopyranosyl‐(4′→2′)‐oligonucleotides show Watson‐Crick pairing comparable in strength to that shown by pyranosyl‐RNA.     

3‐O‐Methylquercetin Glucosides from Ophioglossum pedunculosum and Inhibition of Lipopolysaccharide‐Induced Nitric Oxide Production in RAW 264.7 Macrophages

The three new 3‐O‐methylquercetin glucosides 1 – 3 , together with three known congeners and 3‐O‐methylquercetin, were isolated from the fern Ophioglossum pedunculosum (quercetin=2‐(3,4‐dihydroxyphenyl)‐3,5,7‐trihydroxy‐4H‐1‐benzopyran‐4‐one). The new compounds were identified on the basis of spectroscopic analysis as 5′‐isoprenyl‐3‐O‐methylquercetin 4′,7‐di‐β‐D ‐glucopyranoside ( 1 ), 3‐O‐methylquercetin 4′‐β‐D ‐glucopyranoside 7‐[O‐β‐D ‐glucopyranosyl‐(1→2)‐β‐D ‐glucopyranoside] ( 2 ), and 3‐O‐methylquercetin 7‐[O‐β‐D ‐glucopyranosyl‐(1→2)‐β‐D ‐glucopyranoside] ( 3 ). The effect of the isolated compounds on lipopolysaccharide (LPS)‐induced NO production was evaluated. The inhibitory activity of 3‐O‐methylquercetin derivatives decreased markedly with the increasing number of glucosyl groups in the structures.     

Four New Lariciresinol‐Based Lignan Glycosides from the Roots of Rhus javanica var. roxburghiana

The four new lariciresinol‐based lignan glycosides, (?)‐lariciresinol 4′‐(6″‐O‐feruloyl‐β‐D ‐glucopyranoside) ( 1 ), (?)‐lariciresinol 4′‐(4″,6″‐di‐O‐feruloyl‐β‐D ‐glucopyranoside) ( 2 ), 5,5′‐dimethoxylariciresinol 4′‐(4″,6″‐di‐O‐feruloyl)‐β‐D ‐glucopyranoside) ( 3 ), and 4‐O‐[α‐(1,2‐dihydroxyethyl)syringyl]‐5,5′‐dimethoxylariciresinol 4′‐(4″,6″‐di‐O‐feruloyl‐β‐D ‐glucopyranoside) ( 4 ), together with two known ones, lariciresinol 4′‐β‐D ‐glucopyranoside) ( 5 ) and tortoside B ( 6 ), were isolated from the BuOH extract of Rhus javanica var. roxburghiana roots, and their structures were established by means of various spectroscopic techniques.     

Syntheses of β‐C(1→3)‐Glucopyranosides of 2‐ and 4‐Deoxy‐D‐hexoses

The Oshima? Nozaki (Et₂AlI) condensation of isolevoglucosenone ( 4 ) with 2,6‐anhydro‐3,4,5,7‐tetra‐O‐benzyl‐D ‐glycero‐D ‐gulo‐heptose ( 5 ) gave an enone 6 that was converted with high stereoselectivity to 3‐C‐[(1R)‐2,6‐anhydro‐D ‐glycero‐D ‐gulo‐heptitol‐1‐C‐yl]‐2,3‐dideoxy‐D ‐arabino‐hexose ( 1 ; 1 : 1 mixture of α‐ and β‐D ‐pyranose), and to 3‐C‐[(1R)‐2,6‐anhydro‐D ‐glycero‐D ‐gulo‐heptitol‐1‐C‐yl]‐2,3‐dideoxy‐D ‐lyxo‐hexose ( 2 ; 2.7 : 1.4 : 1.0 : 1.4 mixture of α‐D ‐furanose, β‐D ‐furanose, α‐D ‐pyranose, and β‐D ‐pyranose). The Oshima? Nozaki (Et₂AlI) condensation of levoglucosenone ( 17 ) with aldehyde 5 gave an enone 18 that was converted with high stereoselectivity to 3‐C‐[(1R)‐2,6‐anhydro‐D ‐glycero‐D ‐gulo‐heptitol‐1‐C‐yl]‐3,4‐dideoxy‐α‐D ‐arabino‐hexopyranose ( 3 ; single anomer).     

The 5‐Methylisocytosine β‐D‐Ribopyranosyl (4′ → 2′)‐Oligonucleotide

In the context of Eschenmoser's work on pyranosyl‐RNA (‘p‐RNA’), we investigated the synthesis and base‐pairing properties of the 5‐methylisocytidine derivative. The previously determined clear‐cut restrictions of base‐pairing modes of p‐RNA had led to the expectation that a 5‐methylisocytosine β‐D ‐ribopyranosyl (= D ‐pr(^MeisoC)) based (4′ → 2′)‐oligonucleotide would pair inter alia with D ‐pr(isoG) and L ‐pr(G) based oligonucleotides (D ‐pr and L ‐pr = pyranose form of D ‐ and L ‐ribose, resp.). Remarkably, we could not observe pairing with the D ‐pr(isoG) oligonucleotide but only with the L ‐pr(G) oligonucleotide. Our interpretation concludes that this – at first hand surprising – observation is caused by a change in the nucleosidic torsion angle specific for isoC.     

Oligonucleotide Analogues with a Nucleobase‐Including Backbone:, Part 6, 2‐Deoxy‐D‐erythrose‐Derived Phosphoramidites: Synthesis and Incorporation into 14‐Mer DNA Strands

Two modified DNA 14‐mers have been prepared, containing either a 2‐deoxy‐D ‐erythrose‐derived adenosine analogue carrying a C(8)−CH₂O group (deA*), or a 2‐deoxy‐D ‐erythrose‐derived uridine analogue, possessing a C(6)−CH₂O group (deU*). These nucleosides are linked via a phosphinato group between O−C(3′) (deA* and deU*) and O−C(5′) of one neighbouring nucleotide, and between C(8)−CH₂O (deA*), or C(6)−CH₂O (deU*) and O−C(3′) of the second neighbour. N⁶‐Benzoyl‐9‐(β‐D ‐erythrofuranosyl)adenine ( 3 ) and 1‐(β‐D ‐erythrofuranosyl)uracil ( 4 ) were prepared from D ‐glucose, deoxygenated at C(2′), and converted into the required phosphoramidites 1 and 2 . The modified tetradecamers 31 and 32 were prepared by solid‐phase synthesis. Pairing studies show a decrease in the melting temperature of 7 to 8 degrees for the duplexes 31 ⋅ 30 and 32 ⋅ 29 , as compared to the unmodified DNA duplex 29 ⋅ 30 . A comparison with the pairing properties of tetradecamers similarly incorporating deoxyribose‐ instead of the deoxyerythrose‐derived nucleotides evidences that the CH₂OH substituent at C(4′) has no significant effect on the pairing.     

Dapholidins A – C,New Isomeric Biisoflavonoids From Daphne oleoides

Three new isomeric biisoflavonoids, dapholidins A–C ( 1 – 3 , resp.), have been isolated from the AcOEt‐soluble fraction of the MeOH‐soluble extract of the roots of Daphne oleoides, along with the known compounds daphwazirin ( 4 ), daphnetin 8‐O‐β‐D ‐glucopyranoside ( 5 ), daphnin ( 6 ), daphneticin 4″‐O‐β‐D ‐glucopyranoside ( 7 ), and 6,7‐dihydroxy‐3‐methoxy‐8‐[2‐oxo‐2H‐1‐benzopyran‐7‐(O‐β‐D ‐glucopyranosyl)‐8‐yl]‐2H‐1‐benzopyran‐2‐one ( 8 ). The structures of the new compounds were determined by spectroscopic analyses, including 1D‐ and 2D‐NMR.     

Regioselective Benzoylation of 6‐O‐Protected and 4,6‐O‐Diprotected Hexopyranosides as Promoted by Chiral and Achiral Ditertiary 1,2‐Diamines

Monobenzoylation of triols (6‐O‐silylated glycopyranosides) or diols (4,6‐O‐benzylidenated glycopyranosides) with benzoyl chloride and triethylamine at ?60° to 23° is promoted by catalytic amounts of ditertiary 1,2‐diamines. The regioselectivity depends mostly on the structure of the alcohols; it is modulated by the configuration and constitution of the diamines, as shown by comparing the effect of Oriyama's catalyst ((S)‐ 1 and (R)‐ 1 ), N,N,N′,N′‐tetramethylethylenediamine (TMEDA), N,N,N′,N′‐tetraethylethylenediamine (TEEDA), Et₃N, and EtNMe₂. The effect of the catalysts on the reactivity is impaired by their steric hindrance. In agreement with the modest enantioselectivity of the mono‐ and dibenzoylation of rac‐cyclohexane‐1,2‐diol in the presence of Oriyama's catalyst, the influence of these diamines on the regioselectivity is rather limited. While associated with procedural simplicity, these catalysts lead, in a few cases, to higher yields of a single benzoate than established methods, viz. in the preparation of the 3‐O‐benzoyl β‐D ‐glucopyranoside 4 , the 2‐O‐benzoyl α‐D ‐galactopyranoside 22 , the 3‐O‐benzoyl α‐D ‐galactopyranoside 23 , and the benzylidenated 2‐O‐benzoyl α‐D ‐galactopyranoside 44 . The regioselective benzoylation of the benzylidenated β‐D ‐mannopyranoside 47 , leading to 48 , appears to be new.     

Chemo‐Enzymatic Synthesis of 3‐Deoxy‐β‐D‐ribofuranosyl Purines

9‐(3‐Deoxy‐β‐D ‐erythro‐pentofuranosyl)‐2,6‐diaminopurine ( 6 ) was synthesized by an enzymatic transglycosylation of 2,6‐diaminopurine ( 2 ) with 3′‐deoxycytidine ( 1 ) as a donor of 3‐deoxy‐D ‐erythro‐pentofuranose moiety. This transformation comprises i) deamination of 1 to 3′‐deoxyuridine ( 3 ) under the action of whole cell (E. coli BM‐11) cytidine deaminase (CDase), ii) the phosphorolytic cleavage of 3 by uridine phosphorylase (UPase) giving rise to the formation of uracil ( 4 ) and 3‐deoxy‐α‐D ‐erythro‐pentofuranose‐1‐O‐phosphate ( 5 ), and iii) coupling of the latter with 2 catalyzed by whole cell (E. coli BMT‐4D/1A) purine nucleoside phosphorylase (PNPase). Deamination of 6 by adenosine deaminase (ADase) gave 3′‐deoxyguanosine ( 7 ). Treatment of 6 with NaNO₂ afforded 9‐(3‐deoxy‐β‐D ‐erythro‐pentofuranosyl)‐2‐amino‐6‐oxopurine (3′‐deoxyisoguanosine; 8 ). Schiemann reaction of 6 (HF/HBF₄+NaNO₂) gave 9‐(3‐deoxy‐β‐D ‐erythro‐pentofuranosyl)‐2‐fluoroadenine ( 9 ).     

7‐Iodo‐5‐aza‐7‐deazaguanine: Syntheses of Anomeric D‐ and L‐Configured 2‐Deoxyribonucleosides

Iodination of N²‐isobutyryl‐5‐aza‐7‐deazaguanine ( 7 ) with N‐iodosuccinimide (NIS) gave 7‐iodo‐N²‐isobutyryl‐5‐aza‐7‐deazaguanine ( 8 ) in a regioselective reaction (Scheme 1). Nucleobase‐anion glycosylation of 8 with 2‐deoxy‐3,5‐di‐O‐toluoyl‐α‐D ‐ or α‐L ‐erythro‐pentofuranosyl chloride furnished anomeric mixtures of D ‐ and L ‐nucleosides. The anomeric D ‐nucleosides were separated by crystallization to give the α‐D ‐anomer and β‐D ‐anomer with excellent optical purity. Deprotection gave the 7‐iodo‐5‐aza‐7‐deazaguanine 2′‐deoxyribonucleosides 3 (β‐D ; ≥99% de) and 4 (α‐D ; ≥99% de). The reaction sequence performed with the D ‐series was also applied to L ‐nucleosides to furnish compounds 5 (β‐L ; ≥99% de) and 6 (α‐L ; ≥95% de).     

Two New Cytotoxic Nonsulfated Pentasaccharide Holostane (=20‐Hydroxylanostan‐18‐oic Acid γ‐Lactone) Glycosides from the Sea Cucumber Holothuria grisea

Two new lanostane‐type nonsulfated pentasaccharide triterpene glycosides, 17‐dehydroxyholothurinoside A ( 1 ) and griseaside A ( 2 ), were isolated from the sea cucumber Holothuria grisea. Their structures were elucidated by spectroscopic methods, including 2D‐NMR and MS experiments, as well as chemical evidence. Compounds 1 and 2 possess the same pentasaccharide moieties but differ slightly in their side chains of the holostane‐type triterpene aglycone. The structures of the two new glycosides were established as (3β,12α)‐22,25‐epoxy‐3‐{(O‐β‐D ‐glucopyranosyl‐(1→4)‐O‐[O‐3‐O‐methyl‐β‐D ‐glucopyranosyl‐(1→3)‐O‐β‐D ‐glucopyranosyl‐(1→4)‐6‐deoxy‐β‐D ‐glucopyranosyl‐(1→2)]‐β‐D ‐xylopyranosyl)oxy}‐12,20‐dihydroxylanost‐9(11)‐en‐18‐oic acid γ‐lactone ( 1 ) and (3β,12α)‐3‐{(O‐β‐D ‐glucopyranosyl‐(1→4)‐O‐[O‐3‐O‐methyl‐β‐D ‐glucopyranosyl‐(1→3)‐O‐β‐D ‐glucopyranosyl‐(1→4)‐6‐deoxy‐β‐D ‐glucopyranosyl‐(1→2)]‐β‐D ‐xylopyranosyl)oxy}‐12,20,22‐trihydroxylanost‐9(11)‐en‐18‐oic acid γ‐lactone ( 2 ). The 17‐dehydroxyholothurinoside A ( 1 ) and griseaside A ( 2 ) exhibited significant cytotoxicity against HL‐60, BEL‐7402, Molt‐4, and A‐549 cancer cell lines.     

Synthesis and Pairing Properties of 3′‐Deoxyribopyranose (4′→2′)‐Oligonucleotides (‘p‐DNA')

The preparation and the pairing properties of the new 3′‐deoxyribopyranose (4′→2′)‐oligonucleotide (=p‐DNA) pairing system, based on 3′‐deoxy‐β‐D ‐ribopyranose nucleosides is presented. D ‐Xylose was efficiently converted to the prefunctionalized 3‐deoxyribopyranose derivative 4‐O‐[(tert‐butyl)dimethylsilyl]‐3‐deoxy‐D ‐ribopyranose 1,2‐diacetate 8 (obtained as a 4 : 1 mixture of α‐ and β‐D ‐anomers; Scheme 1). From this sugar building block, the corresponding, appropriately protected thymine, guanine, 5‐methylcytosine, and purine‐2,6‐diamine nucleoside phosphoramidites 29 – 32 were prepared in a minimal number of steps (Schemes 2–4). These building blocks were assembled on a DNA synthesizer, and the corresponding p‐DNA oligonucleotides were obtained in good yields after a one‐step deprotection under standard conditions, followed by HPLC purification (Scheme 5 and Table 1). Qualitatively, p‐DNA shows the same pairing behavior as p‐RNA, forming antiparallel, exclusively Watson‐Crick‐paired duplexes that are much stronger than corresponding DNA duplexes. Duplex stabilities within the three related (i.e., based on ribopyranose nucleosides) oligonucleotide systems p‐RNA, p‐DNA, and 3′‐O‐Me‐p‐RNA were compared with each other (Table 2). Intrinsically, p‐RNA forms the strongest duplexes, followed by p‐DNA, and 3′‐O‐Me‐p‐RNA. However, by introducing the nucleobases purine‐2,6‐diamine (D) and 5‐methylcytosine (M) instead of adenine and cytosine, a substantial increase in stability of corresponding p‐DNA duplexes was observed.