2‐Amino‐8‐(2‐deoxy‐2‐fluoro‐β‐d‐arabinofuranosyl)imidazo[1,2‐a][1,3,5]triazin‐4(8H)‐one monohydrate,a 2′‐deoxyguanosine analogue with an altered Watson–Crick recognition site

The title compound, C₁₀H₁₂FN₅O₄·H₂O, shows an anti glycosyl orientation [χ = −123.1 (2)°]. The 2‐deoxy‐2‐fluoroarabinofuranosyl moiety exhibits a major C2′‐endo sugar puckering (S‐type, C2′‐endo–C1′‐exo, ²T₁), with P = 156.9 (2)° and τ_m = 36.8 (1)°, while in solution a predominantly N conformation of the sugar moiety is observed. The conformation around the exocyclic C4′—C5′ bond is −sc (trans, gauche), with γ = −78.3 (2)°. Both nucleoside and solvent molecules participate in the formation of a three‐dimensional hydrogen‐bonding pattern via intermolecular N—H...O and O—H...O hydrogen bonds; the N atoms of the heterocyclic moiety and the F substituent do not take part in hydrogen bonding.     

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.     

Two (Z)‐N‐aryl‐3‐benzylideneisoindolin‐1‐ones

Two isoindolin‐1‐one derivatives, (Z)‐3‐benzyl­idene‐N‐phenyl­isoindolin‐1‐one, C₂₁H₁₅NO, (II), and (Z)‐3‐benzyl­idene‐N‐(4‐methoxy­phenyl)­isoindolin‐1‐one, C₂₂H₁₇NO₂, (III), were synthesized by the palladium‐catalysed heteroannulation. The mol­ecules of both compounds have a Z configuration. The interplanar angles between the five‐ and six‐membered rings of the isoindolinone moiety in (II) and (III) are 1.66 (11) and 2.26 (7)°, respectively. The phenyl rings at the N‐position in (II) and (III) are twisted out of the C₄N ring plane by 62.77 (11) and 67.10 (7)°, respectively. The substitutions at the N and C‐3 positions of the isoindolinone system have little influence on the molecular dimensions of the resulting compounds.     

8‐Aza‐7‐deaza‐7‐propynyladenosine methanol solvate

In the title compound, 4‐amino‐3‐propynyl‐1‐(β‐d ‐ribofur­anosyl)‐1H‐pyrazolo[3,4‐d]pyrimidine methanol solvate, C₁₃H₁₅N₅O₄·CH₃OH, the torsion angle of the N‐glycosylic bond is between anti and high‐anti [χ = −101.8 (5)°]. The ribofuranose moiety adopts the C3′‐endo (³T₂) sugar conformation (N‐type) and the conformation at the exocyclic C—C bond is +sc (gauche, gauche). The propynyl group is out of the plane of the nucleobase and is bent. The compound forms a three‐dimensional network which is stabilized by several hydrogen bonds (O—H·O and O—H·N). The nucleobases are stacked head‐to‐tail. The methanol solvent mol­ecule forms hydrogen bonds with both the nucleobase and the sugar moiety.     

N‐Benzyl‐2′‐iodo­cinnamanilide and N‐benzyl‐2′‐iodo‐4′‐methyl‐2‐phenyl­cinnamanilide

The aromatic ring of the cinnamic moiety in N‐benzyl‐2′‐iodo­cinnamanilide, C₂₂H₁₈INO, (I), and N‐benzyl‐2′‐iodo‐4′‐methyl‐2‐phenyl­cinnamanilide, C₂₉H₂₄INO, (II), makes a dihedral angle with the iodo­phenyl ring of 72.1 (2) and 81.0 (2)° in (I) and (II), respectively. In (I), mol­ecules exist as discrete components, while in (II), they form infinite chains along the b axis, through I?O non‐bonded interactions.     

7‐Deaza‐2′‐deoxyinosine: a nucleoside showing ambiguous base‐pairing properties against the four canonical DNA constituents

The title compound [systematic name: 7‐(2‐deoxy‐β‐d ‐erythro‐pentofuranosyl)‐3,7‐dihydro‐4H‐pyrrolo[2,3‐d]pyrimidin‐4‐one], C₁₁H₁₃N₃O₄, represents an acid‐stable derivative of 2′‐deoxyinosine. It exhibits an anti glycosylic bond conformation, with a χ torsion angle of 113.30 (15)°. The furanose moiety adopts an S‐type sugar pucker ⁴T₃, with P = 221.8 (1)° and τ_m = 40.4 (1)°. The conformation at the exocyclic C4′—C5′ bond of the furanose ring is ap (trans), with γ = 167.14 (10)°. The extended structure forms a three‐dimensional hydrogen‐bond network involving O—H...O, N—H...O and C—H...O hydrogen bonds. The title compound forms an uncommon hydrogen bond between a CH group of the pyrrole system and the ring O atom of the sugar moiety of a neighbouring molecule.     

Regioisomeric 4‐nitroindazole N1‐ and N2‐(β‐d‐ribonucleosides)

The structures of the isomeric nucleosides 4‐nitro‐1‐(β‐d ‐ribo­furan­osyl)‐1H‐indazole, C₁₂H₁₃N₃O₆, (I), and 4‐nitro‐2‐(β‐d ‐ribo­furan­osyl)‐2H‐indazole, C₁₂H₁₃N₃O₆, (II), have been determined. For compound (I), the conformation of the gly­cosylic bond is anti [χ = −93.6 (6)°] and the sugar puckering is C2′‐exo–C3′‐endo. Compound (II) shows two conformations in the crystalline state which differ mainly in the sugar pucker; type 1 adopts the C2′‐endo–C3′‐exo sugar puckering associated with a syn base orientation [χ = 43.7 (6)°] and type 2 shows C2′‐exo–C3′‐endo sugar puckering accompanied by a somewhat different syn base orientation [χ = 13.8 (6)°].     

7‐Iodo‐5‐aza‐7‐deazaguanine ribonucleoside: crystal structure,physical properties,base‐pair stability and functionalization

The positional change of nitrogen‐7 of the RNA constituent guanosine to the bridgehead position‐5 leads to the base‐modified nucleoside 5‐aza‐7‐deazaguanosine. Contrary to guanosine, this molecule cannot form Hoogsteen base pairs and the Watson–Crick proton donor site N3—H becomes a proton‐acceptor site. This causes changes in nucleobase recognition in nucleic acids and has been used to construct stable `all‐purine' DNA and DNA with silver‐mediated base pairs. The present work reports the single‐crystal X‐ray structure of 7‐iodo‐5‐aza‐7‐deazaguanosine, C<sub>10</sub>H<sub>12</sub>IN<sub>5</sub>O<sub>5</sub> ( 1 ). The iodinated nucleoside shows an anti conformation at the glycosylic bond and an N conformation (O4′‐endo) for the ribose moiety, with an antiperiplanar orientation of the 5′‐hydroxy group. Crystal packing is controlled by interactions between nucleobase and sugar moieties. The 7‐iodo substituent forms a contact to oxygen‐2′ of the ribose moiety. Self‐pairing of the nucleobases does not take place. A Hirshfeld surface analysis of 1 highlights the contacts of the nucleobase and sugar moiety (O—H…O and N—H…O). The concept of pK‐value differences to evaluate base‐pair stability was applied to purine–purine base pairing and stable base pairs were predicted for the construction of `all‐purine' RNA. Furthermore, the 7‐iodo substituent of 1 was functionalized with benzofuran to detect motional constraints by fluorescence spectroscopy.     

Ethyl 3‐(2′‐deoxyuridin‐5‐yl)‐3‐hydroxy‐2‐iodopropanoate,a ­nucleoside analogue

In the title compound, C₁₄H₁₉IN₂O₈, an almost planar heterocyclic base is oriented anti with respect to the puckered sugar moiety. The sugar pucker is C2′‐endo/C3′‐exo, the N‐glycosidic torsion angle is 166.4 (4)° and the conformation of O5′ is +sc. The mol­ecules are linked by hydrogen bonds of the types N—H?O and O—H?O.     

1‐(2‐Deoxy‐β‐d‐erythro‐pento­furan­osyl)‐4‐nitro‐1H‐indazole

In the title compound, C₁₂H₁₃N₃O₅, the conformation of the gly­cosyl­ic bond is anti [torsion angle = −105.3 (2)°]. The 2′‐deoxy­ribo­furan­ose moiety adopts an S‐type sugar pucker and the orientation of the exocyclic C—C bond is −sc (trans).     

Synthesis of a Fusion‐Isomeric Cellobionoimidazole and Its Evaluation against the syn‐Protonating Glycosidase Cel7A

The fusion‐isomeric cellobinoimidazole 2 , a potential inhibitor of the syn‐protonating β‐glycosidase Cel7A, was synthesised by Koenigs–Knorr glycosylation of the α‐D ‐arabinopyranoside 32 , followed by selective hydrolysis. Glycosylation of 32 with acetobromoglucose 6 proceeded with poor diastereoselectivity, giving the desired 1,3‐linked β‐d‐ disaccharide 35 as minor product, besides the major 1,3‐linked α‐d‐ disaccharide 36 . Hg²⁺‐Promoted glycosylation of 32 led predominantly to the 1,2‐ortho ester 33 . Sequential removal of the silyl, acetyl, and allyl groups of 35 led to a 45 : 55 equilibrium mixture 2 and the manno‐configured isomer 39 . Similarly, deprotection of 36 gave a mixture of the maltonoimidazole 42 and the manno‐configured isomer 43 . According to a known protocol, the glycosyl acceptor 32 was synthesised in eleven steps and an overall yield of 8–13% from D ‐lyxose. The silylated arabinopyranosyl moiety of the α‐d‐ glucosides 13 – 19, 33, 34 , and 36 adopts a ⁴C₁ conformation, while the arabinopyranosyl moiety of the β‐d‐ glucosides 17 and 35 exists as a 1 : 3 mixture of ⁴C₁ and ¹C₄ conformers, as a result of the combined preferred axial orientation of bulky vicinal substituents and the anomeric effect. MM3* Modelling evidences a preferred ⁴C₁ conformation of 35 and 36 , and stronger steric interactions between the pyranosyl moieties of 35 . The equilibrium mixture 2 / 39 proved a poor inhibitor of Cel7A with an IC₅₀ value of ca. 4 mM .     

2′‐Deoxy‐5‐methylisocytidine

In the title compound, 2‐amino‐1‐(2‐deoxy‐β‐d ‐erythro‐pento­furan­osyl)‐5‐methyl­pyrimidin‐4(1H)‐one, C₁₀H₁₅N₃O₄, the conformation of the N‐glycosidic bond is syn and the 2‐deoxy­ribo­furan­ose moiety adopts an unusual ^OT₁ sugar pucker. The orientation of the exocyclic C4′—C5′ bond is +sc (+gauche).     

6‐Aza‐2′‐deoxy­uridine and N3‐anisoyl‐6‐aza‐2′‐deoxy­uridine

In 2‐(2‐deoxy‐β‐d ‐erythro‐pentofuranosyl)‐1,2,4‐triazine‐3,5(2H,4H)‐dione (6‐aza‐2′‐deoxy­uridine), C₈H₁₁N₃O₅, (I), the conformation of the glycosylic bond is between anti and high‐anti [χ = −94.0 (3)°], whereas the derivative 2‐(2‐deoxy‐β‐d ‐erythro‐pentofuranosyl)‐N⁴‐(2‐methoxy­benzoyl)‐1,2,4‐triazine‐3,5(2H,4H)‐dione (N³‐anisoyl‐6‐aza‐2′‐deoxy­uridine), C₁₆H₁₇N₃O₇, (II), displays a high‐anti conformation [χ = −86.4 (3)°]. The furanosyl moiety in (I) adopts the S‐type sugar pucker (²T₃), with P = 188.1 (2)° and τ_m = 40.3 (2)°, while the sugar pucker in (II) is N (³T₄), with P = 36.1 (3)° and τ_m = 33.5 (2)°. The crystal structures of (I) and (II) are stabilized by inter­molecular N—H⋯O and O—H⋯O inter­actions.     

3,4‐Di­hydro‐6‐methyl‐3‐β‐d‐ribo­furan­osyl‐4,5′‐cyclo‐9H‐imidazo[1,2‐a]­purin‐9‐one hydrate

In the title compound, C₁₃H₁₃N₅O₄·H₂O (4,5′‐cyclo­wyosine·H₂O), the cyclization forces a syn arrangement of the aglycon with respect to the sugar moiety. The ribo­furan­ose part of the mol­ecule displays a β‐d configuration with an envelope C1′‐endo pucker. The mol­ecules are arranged in columns along the short a axis and are linked to water mol­ecules through O—H?O and O—H?N hydrogen bonds.     

9,10‐Di­phenyl‐9,10‐epi­dioxy­anthra­cene and 9,10‐di­hydro‐10,10‐di­methoxy‐9‐phenyl­anthracen‐9‐ol

9,10‐Di­phenyl‐9,10‐epi­dioxy­anthracene, C₂₆H₁₈O₂, (I), was accidentally used in a photo­oxy­genation reaction that produced 9,10‐di­hydro‐10,10‐di­methoxy‐9‐phenyl­anthracen‐9‐ol, C₂₂H₂₀O₃, (II). In both compounds, the phenyl rings are approximately orthogonal to the anthracene moiety. The conformation of the anthracene moiety differs as a result of substitution. Intramolecular C—H⃛O interactions in (I) form two approximately planar S(5) rings in each of the two crystallographically independent mol­ecules. The packing of (I) and (II) consists of molecular dimers stabilized by C—H⃛O interactions and of molecular chains stabilized by O—H⃛O interactions, respectively.     

The N1‐(2′‐deoxyribofuranoside) of 3‐iodo‐5‐nitroindole: a universal nucleoside forming nitro–iodo interactions

The title compound [systematic name: 1‐(2‐deoxy‐β‐d ‐erythro‐pentofuranosyl)‐3‐iodo‐5‐nitro‐1H‐indole], C₁₃H₁₃IN₂O₅, exhibits an anti glycosylic bond conformation with a χ torsion angle of −114.9 (3)°. The furanose moiety shows a twisted C2′‐endo sugar pucker (S‐type), with P = 141.3° and τ_m = 40.3°. The orientation of the exocyclic C4′—C5′ bond is +ap (gauche, trans), with a γ torsion angle of 177.4 (2)°. The extended crystal structure is stabilized by hydrogen bonding and I...O contacts, as well as by stacking interactions. The O atoms of the nitro group act as acceptors, forming bifurcated hydrogen bonds within the ac plane. Additionally, the iodo substituent forms an interplanar contact with an O atom of the nitro group, and another contact with the O atom of the 5′‐hydroxy group of the sugar moiety within the ac plane is observed. These contacts can be considered as the structure‐determining factors for the molecular packing in the crystal structure.     

7‐Iodo‐8‐aza‐7‐deaza‐2′‐deoxy­adenosine and 7‐bromo‐8‐aza‐7‐deaza‐2′‐deoxyadenosine

The isomorphous structures of the title molecules, 4‐amino‐1‐(2‐deoxy‐β‐d ‐erythro‐pento­furan­osyl)‐3‐iodo‐1H‐pyrazolo‐[3,4‐d]pyrimidine, (I), C₁₀H₁₂IN₅O₃, and 4‐amino‐3‐bromo‐1‐(2‐deoxy‐β‐d ‐erythro‐pento­furan­osyl)‐1H‐pyrazolo[3,4‐d]­pyrimidine, (II), C₁₀H₁₂BrN₅O₃, have been determined. The sugar puckering of both compounds is C1′‐endo (^1′E). The N‐­glycosidic bond torsion angle χ¹ is in the high‐anti range [?73.2 (4)° for (I) and ?74.1 (4)° for (II)] and the crystal structure is stabilized by hydrogen bonds.     

2‐(2‐Naphthyl­oxy)­acetate derivatives. II. A new class of antiamnesic agents

The title compounds, 4‐(2‐naphthyl­oxy­methyl­carbonyl)­morpholine, C₁₆H₁₇NO₃, (I), and 4‐methyl‐1‐(2‐naphthyl­oxy­methyl­carbonyl)­piper­azine, C₁₇H₂₀N₂O₂, (II), are potential antiamnesics. The morpholine ring in (I) and the piperazine ring in (II) adopt chair conformations. In (I), the mol­ecules are linked by weak intermolecular C—H⃛O interactions into chains that have a graph‐set motif of C(10), while in (II), the mol­ecules are linked by weak intermolecular C—H⃛O interactions that generate two C(7) graph‐set motifs. The dihedral angle between the naphthalene moiety and the best plane through the morpholine ring is 20.62 (4)° in (I), while the naphthalene moiety is oriented nearly perpendicular to the mean plane of the piperazine ring in (II).     

3,3′‐[o‐Phenyl­enebis­(methyl­eneoxy)]­bis(6‐chloro­flavone) and 3,3′‐propyl­ene­dioxy­bis­[6‐chloro‐2‐(2‐furyl)‐4H‐1‐benzopyran‐4‐one]

The title compound 3,3′‐[o‐phenyl­enebis­(methyl­eneoxy)]­bis(6‐chloro­flavone), C₃₈H₂₄Cl₂O₆, (I), crystallizes in the monoclinic space group C2/c, with the molecules lying across twofold rotation axes so that there is half a mol­ecule in the asymmetric unit, while the other title compound, 3,3′‐propyl­ene­dioxy­bis­[6‐chloro‐2‐(2‐furyl)‐4H‐1‐benzopyran‐4‐one], C₂₉H₁₈Cl₂O₈, (II), crystallizes in monoclinic space group P2₁/n with one mol­ecule in the asymmetric unit. In both compounds, the benzopyran moiety is nearly planar, with dihedral angles between the two fused rings of 1.43 (8)° in (I), and 2.54 (7) and 3.00 (6)° with respect to the benzopyran moieties in the two halves of (II). The furan rings are twisted by 8.3 (1) and 8.4 (1)° in the two halves of (II). In both compounds, the molecular structure is stabilized by intramolecular C—H⃛O hydrogen bonds, while the crystal packing is stabilized by C—H⃛Cl and C—H⃛O intermolecular hydrogen bonds in (I) and (II), respectively.     

2‐Bromo‐1,3‐bis[2‐(2‐naphthyl)vinyl]benzene benzene hemisolvate and 9‐bromodinaphth[1,2‐a:2′,1′‐j]anthracene

2‐Bromo‐1,3‐bis[2‐(2‐naphthyl)vinyl]benzene benzene hemisolvate, C₃₀H₂₁Br·0.5C₆H₆, (I), with two formula units in the asymmetric unit, exists in the crystal structure in a conformation in which the trans (2‐naphthyl)vinyl substituents on the central bromobenzene moiety appear as nearly fully extended `wings', while 9‐bromodinaphth[1,2‐a:2′,1′‐j]anthracene, C<sub>30</sub>H<sub>17</sub>Br, (II), adopts a highly nonplanar `manta‐ray' shape, with the H atoms in the interior of the molecule within van der Waals contact distances. The packing of the significantly twisted molecules of (I) generates large voids which are filled by benzene solvent molecules, while molecules of (II) stack compactly with all C—Br bonds parallel within the stack.