Oligonucleosides with a Nucleobase‐Including Backbone,Part 3, Synthesis of Acetyleno‐Linked Adenosine Dimers

The adenosine‐derived dimers 14a – d and 15b – d have been prepared by coupling the protected 8‐iodoadenosines 3 and 13 with the C(5′)‐ethynylated adenosine derivatives 5 , 6 , 11 , and 12 (Scheme 4). Similarly, the 5′‐epimeric dimer 16 was prepared by coupling 3 with the alkyne 8 (Scheme 5). The propargylic alcohol 4 was transformed into the N‐benzoylated alkyne 5 and into the amine 6 , while the epimeric alcohol 7 was converted to the epimeric amine 8 and the 5′‐deoxy analogues 11 and 12 (Scheme 3). Cross‐coupling of the iodoadenosine 13 with the alkyne 5 to 14a was optimised; it is influenced by the N‐benzoyl and the Et₃SiO group of the alkyne, but hardly by the N‐benzoyl group of the 8‐iodoadenosine. The alkyne is most reactive when it is O‐silylated, but not N‐benzoylated. Cross‐coupling of the 5′‐deoxyalkynes proceeded more slowly. The dimers 14a – d , 15b – d , and 16 were obtained in good yields (Table 2). Deprotection of 14d and 16 led to 18 and 20 , respectively (Scheme 5). The diols 17 and 19 and the hexols 18 and 20 prefer the syn‐conformation in (D₆)DMSO, completely for unit II and ≥80% for unit I; they exhibit partially persistent intramolecular O(5′)−H⋅⋅⋅N(3) H‐bonds. The persistence increases from 18% (unit I of 19 ), 32% (unit II of 17 and 19 ), 45% (unit I of 17 ), 52% (unit II of 18 and 20 ), and 55% (unit I of 20 ) to 82% (unit I of 18 ).     

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 32

The G[s ]G dinucleoside 6 and the G[s ]G* dinucleoside 8 were prepared by alkylation of the guanosine thiols derived from 2 and 5 , respectively, by the C(8)‐chloromethylated guanosine 4 that was obtained from alcohol 3 . Dinucleosides 6 and 8 were deacylated to 7 and 9 , and fully deprotected to 10 and 11 , respectively. The G[n ]G dinucleoside 16 was obtained by reductive amination of aldehyde 13 with an iminophosphorane derived from azide 14 and deprotection of the resulting dimer 15 . In the solid state of 6 , and in a solution of 6 and 8 in CDCl₃, H? N(1/I) and H? N(1/II) are engaged in intramolecular H‐bonds to the C?O of the isobutyryl protecting groups, and HN of the isobutyryl group of unit I forms an interresidue, intramolecular H‐bond to N(7/II), leading to a syn orientation of the nucleobase at unit I, to a tg orientation of the sulfanyl moiety, and to an orthogonal orientation of the nucleobases, preventing any base pairing. The silylated and isopropylidenated dinucleosides 7 and 9 are present in DMSO solution as solvated monoplexes. Broad ¹H‐NMR signals of the nucleosides 7 and 16 in CHCl₃ solution evidence equilibrating G‐quadruplexes. The quadruplex formation of 7 and 16 was established by ¹H‐NMR spectroscopy (only of 16 ), vapour pressure osmometry, mass spectrometry, and CD spectroscopy. The C(6(I))‐hydroxymethylated analogue 9 in CDCl₃ and the fully deprotected dinucleosides 10 and 11 in H₂O form only weakly π? π stacked associates, but no G‐quadruplexes, as evidenced by CD spectroscopy.     

Optically active diaryl tetrahydroisoquinoline derivatives

In (1R,3S)‐6,7‐dimethoxy‐3‐(methoxydiphenylmethyl)‐1‐phenyl‐1,2,3,4‐tetrahydroisoquinoline, C₃₁H₃₁NO₃, (I), and (1R,3S)‐2‐benzyl‐3‐[diphenyl(trimethylsiloxy)methyl]‐6,7‐dimethoxy‐1‐phenyl‐1,2,3,4‐tetrahydroisoquinoline, C₄₀H₄₃NO₃Si, (II), the absolute configurations have been confirmed to be R and S at the isoquinoline 1‐ and 3‐positions, respectively, by NMR spectroscopy experiments. Both structures have monoclinic (P2₁) symmetry and the N‐containing six‐membered ring assumes a half‐chair conformation. The asymmetric unit of (I) contains one molecule, while (II) has two molecules within the asymmetric unit. These structures are of interest with respect to the conformation around the exocyclic C—C bond: (I) displays an ap (antiperiplanar) conformation, while (II) displays an sc‐exo (synclinal) conformation around this bond. These conformations are significant for stereocontrol when these compounds are used as catalysts. Various C—H...π and C—H...O bonds link the molecules together in the crystal structure of (I). In the crystal structure of (II), three intermolecular C—H...π hydrogen bonds help to establish the packing.     

Methyl 2‐acetamido‐2‐deoxy‐β‐d‐glucopyranoside dihydrate and methyl 2‐formamido‐2‐deoxy‐β‐d‐glucopyranoside

Methyl 2‐acetamido‐2‐deoxy‐β‐d ‐glucopyranoside (β‐GlcNAcOCH₃), (I), crystallizes from water as a dihydrate, C₉H₁₇NO₆·H₂O, containing two independent molecules [denoted (IA) and (IB)] in the asymmetric unit, whereas the crystal structure of methyl 2‐formamido‐2‐deoxy‐β‐d ‐glucopyranoside (β‐GlcNFmOCH₃), (II), C₈H₁₅NO₆, also obtained from water, is devoid of solvent water molecules. The two molecules of (I) assume distorted ⁴C₁ chair conformations. Values of ϕ for (IA) and (IB) indicate ring distortions towards B_C2,C5 and ^C3,O5B, respectively. By comparison, (II) shows considerably more ring distortion than molecules (IA) and (IB), despite the less bulky N‐acyl side chain. Distortion towards B_C2,C5 was observed for (II), similar to the findings for (IA). The amide bond conformation in each of (IA), (IB) and (II) is trans, and the conformation about the C—N bond is anti (C—H is approximately anti to N—H), although the conformation about the latter bond within this group varies by ∼16°. The conformation of the exocyclic hydroxymethyl group was found to be gt in each of (IA), (IB) and (II). Comparison of the X‐ray structures of (I) and (II) with those of other GlcNAc mono‐ and disaccharides shows that GlcNAc aldohexopyranosyl rings can be distorted over a wide range of geometries in the solid state.     

A toyocamycin analogue with the sugar moiety in a syn conformation

The title compound [systematic name: 4‐amino‐5‐cyano‐1‐(β‐d ‐ribofuranosyl)‐7H‐pyrrolo[2,3‐d]pyrimidine hemihydrate], C₁₂H₁₃N₅O₄·0.5H₂O, is a regioisomer of toyocamycin with the ribofuranosyl residue attached to the pyrimidine moiety of the heterocycle. This analogue exhibits a syn glycosylic bond conformation with a χ torsion angle of 57.51 (17)°. The ribofuranose moiety shows an envelope C2′‐endo (²E) sugar conformation (S‐type), with P = 161.6 (2)° and τ_m = 41.3 (1)°. The conformation at the exocyclic C4′—C5′ bond is +sc (gauche, gauche), with a γ torsion angle of 54.4 (2)°. The crystal packing is stabilized by intermolecular O—H...O, N—H...N and O—H...N hydrogen bonds; water molecules, located on crystallographic twofold axes, participate in interactions. An intramolecular O—H...N hydrogen bond stabilizes the syn conformation of the nucleoside.     

Exo conformers of N‐(pyridin‐2‐yl)‐ and N‐(pyridin‐3‐yl)norbornene‐5,6‐dicarboximide crystals

Two isomeric pyridine‐substituted norbornenedicarboximide derivatives, namely N‐(pyridin‐2‐yl)‐exo‐norbornene‐5,6‐dicarboximide, (I), and N‐(pyridin‐3‐yl)‐exo‐norbornene‐5,6‐dicarboximide, (II), both C₁₄H₁₂N₂O₄, have been crystallized and their structures unequivocally determined by single‐crystal X‐ray diffraction. The molecules consist of norbornene moieties fused to a dicarboximide ring substituted at the N atom by either pyridin‐2‐yl or pyridin‐3‐yl in an anti configuration with respect to the double bond, thus affording exo isomers. In both compounds, the asymmetric unit consists of two independent molecules (Z′ = 2). In compound (I), the pyridine rings of the two independent molecules adopt different conformations, i.e. syn and anti, with respect to the methylene bridge. The intermolecular contacts of (I) are dominated by C—H...O interactions. In contrast, in compound (II), the pyridine rings of both molecules have an anti conformation and the two independent molecules are linked by carbonyl–carbonyl interactions, as well as by C—H...O and C—H...N contacts.     

Oligosaccharide Analogues of Polysaccharides,Part 20 , NMR Analysis of Templated Cellodextrins Possessing Two Parallel Chains: A Mimic for Cellulose I?

Naphthalene‐1‐ethanol and naphthalene‐1,8‐diethanol carrying one or two glycosidically bonded cellodextrin chains, T‐x and T‐x‐x , resp. ( x =1 – 4, 8) were analyzed by NMR spectroscopy. For solutions in (D₆)DMSO and (D₅)pyridine, analysis was based on a comparison of chemical shifts, coupling constants, temperature dependence of OH signals, and ROESY spectra of the singly and doubly substituted T‐x and T‐x‐x . The characteristic strong intrachain inter‐residue O(3)−H⋅⋅⋅O(5′) H‐bond of celluloses was detected in the singly and doubly substituted naphthalenes. Also detected was a weakly persistent flip‐flop H‐bond between HO(2′) and HO(6). Weak interchain interactions were, however, observed only for the units closest to the link of T‐x‐x in (D₆)DMSO and for parallel units of T‐1‐1 and T‐3‐3 in (D₅)pyridine. Interchain interactions in T‐x‐x are stronger in (D₅)pyridine than in (D₆)DMSO and decrease with increasing distance from the link. The solid‐state CP/MAS ¹³C‐NMR spectra of T‐x‐x were compared with those of T‐x and of celluloses. The spectrum of T‐8 and, surprisingly, also of T‐8‐8 strongly resembles that of cellulose II and not that of cellulose I_β, evidencing that a flexible template possessing parallel cellodextrin chains does not impose sufficient constraints on the structure of supramolecular assemblies to mimic cellulose I_β, but leads to a valuable mimic of cellulose II.     

Effect of Temperature and Solvent on the Structure of Amide Cavitands

Conformational changes of amide cavitands A – C were investigated at varied temperatures and in several solvents. While cavitands A and B , with comparatively smaller substituents such as Et and ⁱPr, were always in vase conformation in non‐polar solvents such as CDCl₃, CD₂Cl₂, (D₈)THF, and C₆D₆, their thermoswitching (vase to kite) was observed in polar solvents such as (D₇)DMF and (D₆)DMSO or in the presence of acid (TFA) and H‐bonding inhibitor (TFE). Intra‐ and interannular H‐bonds of A and B were clearly observed by low‐temperature ¹H‐NMR spectra in CDCl₃. No conformational change of cavitand C with bigger substituent (^tBu) was observed under any tested temperature range and in polar or non‐polar solvents; C was always in the kite conformation.     

Four oxoindole‐linked α‐alkoxy‐β‐amino acid derivatives

Four structures of oxoindolyl α‐hydroxy‐β‐amino acid derivatives, namely, methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐methoxy‐2‐phenylacetate, C₂₄H₂₈N₂O₆, (I), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐ethoxy‐2‐phenylacetate, C₂₅H₃₀N₂O₆, (II), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐[(4‐methoxybenzyl)oxy]‐2‐phenylacetate, C₃₁H₃₄N₂O₇, (III), and methyl 2‐[(anthracen‐9‐yl)methoxy]‐2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐phenylacetate, C₃₈H₃₆N₂O₆, (IV), have been determined. The diastereoselectivity of the chemical reaction involving α‐diazoesters and isatin imines in the presence of benzyl alcohol is confirmed through the relative configuration of the two stereogenic centres. In esters (I) and (III), the amide group adopts an anti conformation, whereas the conformation is syn in esters (II) and (IV). Nevertheless, the amide group forms intramolecular N—H...O hydrogen bonds with the ester and ether O atoms in all four structures. The ether‐linked substituents are in the extended conformation in all four structures. Ester (II) is dominated by intermolecular N—H...O hydrogen‐bond interactions. In contrast, the remaining three structures are sustained by C—H...O hydrogen‐bond interactions.     

2′‐Deoxyimmunosine: a thiazolo[4,5‐d]pyrimidine nucleoside adopting the syn conformation

The title compound [systematic name: 5‐amino‐3‐(2‐deoxy‐β‐d ‐erythro‐pentofuranosyl)thiazolo[4,5‐d]pyrimidine‐2,7‐(3H,6H)‐dione], C₁₀H₁₂N₄O₅S, exhibits a syn glycosylic bond conformation, with a torsion angle χ of 61.0 (3)°. The furanose moiety adopts the N‐type sugar pucker (³T₄), with P = 33.0 (5)° and τ_m = 15.1 (1)°. The conformation at the exocyclic C4′—C5′ bond is +ap (trans), with the torsion angle γ = 176.71 (14)°. The extended structure is a three‐dimensional hydrogen‐bond network involving O—H...O and N—H...O hydrogen bonds.     

Similar molecular constitutions but different conformations and different supramolecular assemblies in two related fused tetracyclic benzo[b]pyrimido[5,4‐f]azepine derivatives

A simple and effective two‐step approach to tricyclic pyrimidine‐fused benzazepines has been adapted to give the tetracyclic analogues. In (RS)‐8‐chloro‐6‐methyl‐1,2,6,7‐tetrahydropyrimido[5′,4′:6,7]azepino[3,2,1‐hi]indole, C₁₅H₁₄ClN₃, (I), the five‐membered ring adopts an envelope conformation, as does the reduced pyridine ring in (RS)‐9‐chloro‐7‐methyl‐2,3,7,8‐tetrahydro‐1H‐pyrimido[5′,4′:6,7]azepino[3,2,1‐ij]quinoline, C₁₆H₁₆ClN₃, (II). However, the seven‐membered rings in (I) and (II) adopt very different conformations, with the result that the methyl substituent occupies a quasi‐axial site in (I) but a quasi‐equatorial site in (II). The molecules of (I) are linked by C—H...N hydrogen bonds to form C(5) chains and inversion‐related pairs of chains are linked by a π–π stacking interaction. A combination of a C—H...π hydrogen bond and two C—Cl...π interactions links the molecules of (II) into complex sheets. Comparisons are made with some similar fused heterocyclic compounds.     

A three‐dimensional hydrogen‐bonded framework in 2‐amino‐6‐(N‐methylanilino)pyrimidin‐4(3H)‐one and a ribbon of fused hydrogen‐bonded rings in 2‐amino‐6‐(N‐methylanilino)‐5‐nitropyrimidin‐4(3H)‐one

The molecular dimensions of both 2‐amino‐6‐(N‐methylanilino)pyrimidin‐4(3H)‐one, C₁₁H₁₂N₄O, (I), and 2‐amino‐6‐(N‐methylanilino)‐5‐nitropyrimidin‐4(3H)‐one, C₁₁H₁₁N₅O₃, (II), are consistent with considerable polarization of the molecular–electronic structures. The molecules of (I) are linked into a three‐dimensional framework by a combination of one N—H...N hydrogen bond, two independent N—H...O hydrogen bonds and one C—H...π(arene) hydrogen bond. The molecules of (II) are linked into ribbons containing three types of edge‐fused ring by the combination of two independent three‐centre N—H...(O)₂ hydrogen bonds.     

Three styryl‐substituted tetrahydro‐1,4‐epoxy‐1‐benzazepines: configurations,conformations and hydrogen‐bonded chains

(2SR,4RS)‐7‐Chloro‐2‐exo‐[(E)‐styryl]‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, C₁₈H₁₆ClNO, (I), crystallizes as a racemic twin in the space group P2₁ and the molecules are linked into a chain of edge‐fused R₃³(9) rings by a combination of C—H...O and C—H...N hydrogen bonds. The diastereoisomer (2RS,4RS)‐7‐chloro‐2‐endo‐[(E)‐styryl]‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, (II), also crystallizes as a racemic twin, but in the space group P2₁2₁2₁, and a two‐centre C—H...N hydrogen bond and a three‐centre C—H...(O,N) hydrogen bond combine to link the molecules into a complex chain of rings. In (2R,4R)‐7‐fluoro‐2‐endo‐[(E)‐styryl]‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, C₁₈H₁₆FNO, (III), which is not isomorphous with (II), the molecules are linked by a single C—H...O hydrogen bond into simple chains, but the molecular arrangements in (II) and (III) are nonetheless very similar. The significance of this study lies in its observation of the variations in molecular configuration and conformation, and in the variation in the supramolecular aggregation, consequent upon modest changes in the peripheral substituents.     

7‐Amino‐1‐(2‐deoxy‐β‐erythro‐pentofuranosyl)‐1H‐1,2,3‐triazolo[4,5‐d]pyrimidine: an 8‐azaadenine nucleoside with the nucleobase in a syn conformation

The title compound, C₉H₁₂N₆O₃, shows a syn‐glycosylic bond orientation [χ = 64.17 (16)°]. The 2′‐deoxyfuranosyl moiety exhibits an unusual C1′‐exo–O4′‐endo (₁T⁰; S‐type) sugar pucker, with P = 111.5 (1)° and τ_m = 40.3 (1)°. The conformation at the exocyclic C4′—C5′ bond is +sc (gauche), with γ = 64.4 (1)°. The two‐dimensional hydrogen‐bonded network is built from intermolecular N—H...O and O—H...N hydrogen bonds. An intramolecular bifurcated hydrogen bond, with an amino N—H group as hydrogen‐bond donor and the ring and hydroxymethyl O atoms of the sugar moiety as acceptors, constrains the overall conformation of the nucleoside.     

Conformational flexibility in amidophosphoesters: a CSD analysis completed with two new crystal structures of (C6H5O)2P(O)X [X = NHC7H13 and N(CH2C6H5)2]

The crystal structures of diphenyl (cycloheptylamido)phosphate, C₁₉H₂₄NO₃P or (C₆H₅O)₂P(O)(NHC₇H₁₃), ( I ), and diphenyl (dibenzylamido)phosphate, C₂₆H₂₄NO₃P or (C₆H₅O)₂P(O)[N(CH₂C₆H₅)₂], ( II ), are reported. The NHC₇H₁₃ group in ( I ) provides two significant hydrogen‐donor sites in N—H…O and C—H…O hydrogen bonds, needed for a one‐dimensional hydrogen‐bond pattern along [100] in the crystal, while ( II ), with a (C₆H₅CH₂)₂N moiety, lacks these hydrogen bonds, but its three‐dimensional supramolecular structure is mediated by C—H…π interactions. The conformational behaviour of the phenyl rings in ( I ), ( II ) and analogous structures from the Cambridge Structural Database (CSD) were studied in terms of flexibility, volume of the other group attached to phosphorus and packing forces. From this study, synclinal (±sc), anticlinal (±ac) and antiperiplanar (±ap) conformations were found to occur. In the structure of ( II ), there is an intramolecular C_ortho—H…O interaction that imposes a +sc conformation for the phenyl ring involved. For the structures from the CSD, the +sc and ±ap conformations appear to be mainly imposed by similar C_ortho—H…O intramolecular interactions. The large contribution of the C…H/H…C contacts (32.3%) in the two‐dimensional fingerprint plots of ( II ) is a result of the C—H…π interactions. The differential scanning calorimetry (DSC) analyses exhibit peak temperatures (T_m) at 109 and 81 °C for ( I ) and ( II ), respectively, which agree with the strengths of the intermolecular contacts and the melting points.     

Hirshfeld surface analysis of two new phosphorothioic triamide structures

Hirshfeld surfaces and two‐dimensional fingerprint plots are used to analyse the intermolecular interactions in two new phosphorothioic triamide structures, namely N,N′,N′′‐tris(3,4‐dimethylphenyl)phosphorothioic triamide acetonitrile hemisolvate, P(S)[NHC₆H₃‐3,4‐(CH₃)₂]₃·0.5CH₃CN or C₂₄H₃₀N₃PS·0.5CH₃CN, (I), and N,N′,N′′‐tris(4‐methylphenyl)phosphorothioic triamide–3‐methylpiperidinium chloride (1/1), P(S)[NHC₆H₄(4‐CH₃)]₃·[3‐CH₃‐C₅H₉NH₂]⁺·Cl⁻ or C₂₁H₂₄N₃PS·C₆H₁₄N⁺·Cl⁻, (II). The asymmetric unit of (I) consists of two independent phosphorothioic triamide molecules and one acetonitrile solvent molecule, whereas for (II), the asymmetric unit is composed of three components (molecule, cation and anion). In the structure of (I), the different components are organized into a six‐molecule aggregate through N—H...S and N—H...N hydrogen bonds. The components of (II) are aggregated into a two‐dimensional array through N—H...S and N—H...Cl hydrogen bonds. Moreover, interesting features of packing arise in this structure due to the presence of a double hydrogen‐bond acceptor (the S atom of the phosphorothioic triamide molecule) and of a double hydrogen‐bond donor (the N—H unit of the cation). For both (I) and (II), the full fingerprint plot of each component is asymmetric as a consequence of the presence of three fragments. These analyses reveal that H...H interactions [67.7 and 64.3% for the two symmetry‐independent phosphorothioic triamide molecules of (I), 30.7% for the acetonitrile solvent of (I), 63.8% in the phosphorothioic triamide molecule of (II) and 62.9% in the 3‐methylpiperidinium cation of (II)] outnumber the other contacts for all the components in both structures, except for the chloride anion of (II), which only receives the Cl...H contact. The phosphorothioic triamide molecules of both structures include unsaturated C atoms, thus presenting C...H/H...C interactions: 17.6 and 21% for the two symmetry‐independent phosphorothioic triamide molecules in (I), and 22.7% for the phosphorothioic triamide molecule of (II). Furthermore, the N—H...S hydrogen bonds in both (I) and (II), and the N—H...Cl hydrogen bonds in (II), are the most prominent interactions, appearing as large red spots on the Hirshfeld surface maps. The N...H/H...N contacts in structure (I) are considerable, whereas for (II), they give a negligible contribution to the total interactions in the system.     

Hexakis(prop‐2‐enamide)copper(II) bis(perchlorate) and hexakis(prop‐2‐enamide)manganese(II) bis(perchlorate)

The structures of [Cu(AA)₆](ClO₄)₂, (I), and [Mn(AA)₆](ClO₄)₂, (II) (AA is acrylamide, also known as prop‐2‐enamide; C₃H₅NO), display both intra‐ and intermolecular N—H...O hydrogen bonding. A three‐dimensional network is propagated via the perchlorate counter‐ions. There are two crystallographically independent molecules in the copper complex, with the most significant difference between them being the conformation of one symmetry‐related pair of AA ligands which are in the unusual syn conformation. The copper complex exhibits syn/anti disorder of the =CH₂ group in one pair of symmetry‐related AA ligands. The Cu^II and Mn^II centres are both situated on centres of inversion. The copper complex cation has octahedral coordination geometry with typical Jahn–Teller distortions.     

An X‐ray crystallographic and density functional theory study of (3Z)‐4‐(5‐ethylsulfonyl‐2‐hydroxyanilino)pent‐3‐en‐2‐one and (3Z)‐4‐(5‐tert‐butyl‐2‐hydroxyanilino)pent‐3‐en‐2‐one

The Schiff base enaminones (3Z)‐4‐(5‐ethylsulfonyl‐2‐hydroxyanilino)pent‐3‐en‐2‐one, C₁₃H₁₇NO₄S, (I), and (3Z)‐4‐(5‐tert‐butyl‐2‐hydroxyanilino)pent‐3‐en‐2‐one, C₁₅H₂₁NO₂, (II), were studied by X‐ray crystallography and density functional theory (DFT). Although the keto tautomer of these compounds is dominant, the O=C—C=C—N bond lengths are consistent with some electron delocalization and partial enol character. Both (I) and (II) are nonplanar, with the amino–phenol group canted relative to the rest of the molecule; the twist about the N(enamine)—C(aryl) bond leads to dihedral angles of 40.5 (2) and −116.7 (1)° for (I) and (II), respectively. Compound (I) has a bifurcated intramolecular hydrogen bond between the N—H group and the flanking carbonyl and hydroxy O atoms, as well as an intermolecular hydrogen bond, leading to an infinite one‐dimensional hydrogen‐bonded chain. Compound (II) has one intramolecular hydrogen bond and one intermolecular C=O...H—O hydrogen bond, and consequently also forms a one‐dimensional hydrogen‐bonded chain. The DFT‐calculated structures [in vacuo, B3LYP/6‐311G(d,p) level] for the keto tautomers compare favourably with the X‐ray crystal structures of (I) and (II), confirming the dominance of the keto tautomer. The simulations indicate that the keto tautomers are 20.55 and 18.86 kJ mol⁻¹ lower in energy than the enol tautomers for (I) and (II), respectively.     

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 28

The protected hydrazide‐linked uracil‐ and adenine‐derived tetranucleoside analogues 17, 19 , and 21 were synthesized in solution by coupling the dimeric hydrazines 6 and 10 with the carboxylic acids 7, 11 , and 16 . These hydrazines and acids were obtained by partially deprotecting the hydrazines 5, 9 , and 15 , and these were prepared by coupling the hydrazines 3 and 14 with the carboxylic acids 4 and 8 . The crystal structure analysis of the fully protected UU dimer 5 showed the formation of an antiparallel cyclic duplex with the uracil units H‐bonded via H? N(3) and O?C(2). Stacking interactions were observed between the uracil units with a buckle twist of 30.9°, and between the uracil unit II and the fluoren‐9‐yl group of Fmoc (=9H‐fluoren‐9‐yl)methoxycarbonyl). The hydrazide H? N(3′) and the C?O group of Fmoc form an intramolecular H‐bond. The uracil‐ and adenine‐derived, water‐soluble hydrazide‐linked self‐complementary octamers 23 – 32 and the non‐self‐complementary uracil derived decamer 33 were obtained by coupling the carboxylic acids 4 and 8 on a solid support. ¹H‐NMR Analysis in CDCl₃, mixtures of CDCl₃ and (D₆)DMSO, and (D₈)THF showed that the partially deprotected dimers 5, 6, 12 , and 13 form weakly associated linear duplexes. The partially deprotected tetramers 17 and 18 do not associate. The hydrazide‐linked octamers 23 – 32 do not stack in aqueous solution, and the non‐self‐complementary decamer 33 does not stack with the complementary strands of DNA 43 and RNA 42 . The Cbz‐protected amide‐linked octamers 51 – 56 derived from uracil, adenine, cytosine, and guanine were obtained as the main products by solid‐phase synthesis from the carboxylic acids 46 – 49 . The fully deprotected amide‐linked octamers proved insoluble, and could neither be purified nor analysed.     

1‐(β‐d‐Erythrofuranos­yl)cytidine (β‐erythrocytidine)

1‐(β‐d ‐Erythrofuranosyl)cytidine, C₈H₁₁N₃O₄, (I), a derivative of β‐cytidine, (II), lacks an exocyclic hydroxy­methyl (–CH₂OH) substituent at C4′ and crystallizes in a global conformation different from that observed for (II). In (I), the β‐d ‐erythrofuranosyl ring assumes an E₃ conformation (C3′‐exo; S, i.e. south), and the N‐glycoside bond conformation is syn. In contrast, (II) contains a β‐d ‐ribofuranosyl ring in a ³T₂ conformation (N, i.e. north) and an anti‐N‐glycoside linkage. These crystallographic properties mimic those found in aqueous solution by NMR with respect to furan­ose conformation. Removal of the –CH₂OH group thus affects the global conformation of the aldofuranosyl ring. These results provide further support for S/syn–anti and N/anti correlations in pyrimidine nucleosides. The crystal structure of (I) was determined at 200 K.