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.     

7‐Halogenated 7‐Deaza‐2′‐deoxyxanthine 2′‐Deoxyribonucleosides

The synthesis of the 7‐halogenated derivatives 1b (7‐bromo) and 1c (7‐iodo) of 7‐deaza‐2′‐deoxyxanthosine ( 1a ) is described. A partial Br→I exchange was observed when the demethylation of 6‐methoxy precursor compound 4b was performed with Me₃SiCl/NaI. This reaction is circumvented by the nucleophilic displacement of the MeO group under strong alkaline conditions. The halogenated 7‐deaza‐2′‐deoxyxanthosine derivatives 1b , c show a decreased S‐conformer population of the sugar moiety compared to the nonhalogenated 1a . They are expected to form stronger triplexes when they replace 1a in the 1 ?dA?dT base triplet.     

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.     

Crystallographic characterization of a stable 7‐phosphanorbornadiene‐7‐oxide: 2,3‐benzo‐1,4,5,6,7‐pentaphenyl‐7‐phosphabicyclo[2.2.1] hepta‐2,5‐diene‐7‐oxide

The stable 7‐phosphanorbornadiene derivative, 2,3‐benzo‐1,4,5,6,7‐pentaphenyl‐7‐phosphabicyclo[2.2.1]hepta‐2,5‐diene‐7‐oxide ( 1 ) was synthesized in 45% yield via the Diels‐Alder reaction of pentaphenylphosphole oxide and benzyne. The reaction occurs specifically to give a single isomer, which was characterized by use of X‐ray crystallography and ³¹P NMR spectroscopy. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:182–186, 2000     

7‐De­aza‐2′‐deoxy‐7‐propynyl­guanosine

The title compound, C₁₄H₁₆N₄O₄, adopts the anti conformation at the gly­cosylic bond [χ−117.1 (5)°]. The sugar pucker of the 2′‐deoxy­ribo­furan­osyl moiety is C2′‐endo–C3′‐exo, ²T₃ (S‐type). The orientation of the exocyclic C4′—C5′ bond is +sc (gauche). The propynyl group is linear and coplanar with the nucleobase moiety. The structure of the compound is stabilized by several hydrogen bonds (N—H⋯O and O—H⋯O), leading to the formation of a multi‐layered network. The nucleobases, as well as the propynyl groups, are stacked. This stacking might cause the extraordinary stability of DNA duplexes containing this compound.     

Synthesis of 7‐chloro‐9‐trifluoromethyl‐/7‐fluorophenothiazines

Synthesis of 7‐chloro‐9‐trifluoromethyl‐/7‐fluorophenothiazines is reported by Smiles rearrangement of 5‐chloro‐3‐trifluoromethyl‐/5‐fluoro‐2‐formamido‐2′‐nitrodiphenyl sulfides. The later were obtained by the formylation of 2‐amino‐5‐chloro‐7‐trifluoromethyl‐/5‐fluoro‐2′‐nitrodiphenyl sulfides, which were prepared by the condensation of 2‐amino‐5‐fluoro‐/5‐chloro‐3‐trifluoromethyl benzenethiols with o‐halonitrobenzenes. 1‐Nitrophenothiazines have also been synthesized by the condensation of 2‐aminobenzenethiols with o‐halonitrobenzenes, involving Smiles rearrangement in situ. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:81–86, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20235     

7‐Substituted 7‐Deaza‐2′‐deoxyadenosines and 8‐Aza‐7‐deaza‐2′‐deoxyadenosines: Fluorescence of DNA‐Base Analogues Induced by the 7‐Alkynyl Side Chain

7‐Alkynylated 7‐deazaadenine (pyrrolo[2,3‐d]pyrimidin‐4‐amine) 2′‐deoxyribonucleosides show strong fluorescence which is induced by the 7‐alkynyl side chain (Table 3). A large Stokes shift with an emission around 400 nm is observed when the compound is irradiated at 280 nm. The solvent dependence indicates the formation of a charged transition state. The fluorescence appears when the triple bond is in conjugation with the heterocyclic base. Electron‐donating substituents at the triple bond increase the fluorescence, while electron‐withdrawing residues reduce it. In comparison, the 7‐alkynylated 8‐aza‐7‐deazaadenine (pyrazolo[3,4‐d]pyrimidin‐4‐amine) 2′‐deoxyribonucleosides are rather weakly fluorescent (Table 4). Quantum yields and fluorescence decay times are measured. The synthesis of the 7‐alkynylated 7‐deaza‐2′‐deoxyadenosines and 8‐aza‐7‐deaza‐2′‐deoxyadenosines was performed with 7‐deaza‐2′‐deoxy‐7‐iodoadenosine ( 6 ) or 8‐aza‐7‐deaza‐2′‐deoxy‐7‐iodoadenosine ( 22 ) as starting materials and employing the Pd⁰‐catalyzed cross‐coupling reaction with the corresponding alkynes (Schemes 1, 4, and 5). Catalytic hydrogenation of the side chain of the unsaturated nucleosides 5 and 17 afforded the 7‐alkyl derivatives 18 and 19 , respectively, which do not show significant fluorescence (Scheme 2).     

7‐Vinyl‐8‐aza‐7‐de­aza‐2′‐deoxy­adenosine monohydrate

In the title compound, 4‐amino‐1‐(2‐deoxy‐β‐d ‐eythro‐pento­furan­osyl)‐3‐vinyl‐1H‐pyrazolo­[3,4‐d]­pyrimidine monohydrate, C₁₂H₁₅N₅O₃·H₂O, the conformation of the gly­cosyl bond is anti. The furan­ose moiety is in an S conformation with an unsymmetrical twist, and the conformation at the exocyclic C—C(OH) bond is +sc (gauche, gauche). The vinyl side chain is bent out of the heterocyclic ring plane by 147.5 (5)°. The three‐dimensional packing is stabilized by O—H·O, O—H·N and N—H·O hydrogen bonds.     

Asymmetric anionic polymerizations of 7‐cyano‐7‐alkoxycarbonyl‐1,4‐benzoquinone methides

Asymmetric anionic polymerizations of 7‐cyano‐7‐alkoxycarbonyl‐1,4‐benzoquinone methides ( 1 ) with various alkoxy groups were performed using chiral initiators such as lithium isopropylphenoxide (ⁱPrPhOLi)/(S)‐(–)‐2,2′‐isopropylidene‐bis(4‐phenyl‐2‐oxazoline) ((–)‐PhBox) and lithium isopropylphenoxide (ⁱPrPhOLi)/(–)‐sparteine ((–)‐Sp) to investigate the effect of the alkoxy groups of alkoxycarbonyl substituent in the monomers 1 and chiral ligands of chiral initiators on the control of chiral center in the formation of polymers. Molar optical rotation values of the polymers were significantly dependent upon alkoxy groups, and the polymers with higher molar optical rotation were obtained in monomers with primary alkoxy groups. The asymmetric anionic oligomerizations of the quinone methides having methoxy( 1a ), ethoxy( 1b ), and n‐propoxy( 1c ) groups with chiral initiators were carried out. Both 1‐mers and 2‐mers were isolated and their optical resolutions were performed to determine the extent of stereocontrol. High stereoselectivity was observed at the propagation reaction, but not at the initiation reaction. The effect of the counterion on the control of chiral center in the formation of the polymer was investigated in the asymmetric anionic polymerizations of 1b with ⁱPrPhOM(M = Li, Na, K)/(–)‐Sp and ⁱPrPhOM(M = Li, Na, K)/(–)‐PhBox initiators and discussed. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

7‐Phenyl‐1‐oxa‐4‐thiaspiro[4.5]decan‐7‐ol stereoisomers

The stereoisomers of 7‐phenyl‐1‐oxa‐4‐thia­spiro­[4.5]­decan‐7‐ol, C₁₄H₁₈O₂S, have the same stereochemistry at the C atom bearing an OH group, i.e. axial OH and equatorial phenyl groups. However, the acetal S and O atoms are axial and equatorial, respectively, in one isomer and reversed in the second. Furthermore, the crystals of one isomer are composed of hydrogen‐bonded mol­ecules involving the hydroxyl H atom and the O atom of the five‐membered heterocyclic ring, with an O?O distance of 2.962 (3) Å, forming a polymeric chain along the b axis. The asymmetric unit of the other isomer is composed of two mol­ecules, wherein hydroxyl H atoms and the O atoms of the five‐membered heterocyclic rings display intramolecular O—H?O hydrogen bonds with O?O separations of 2.820 (2) and 2.834 (2) Å.     

Preparation of 5‐methyl‐2‐sulfanyl‐7h‐1,3,4‐thiadiazolo[3,2‐a]‐pyrimidin‐7‐ones

7H‐1,3,4‐Thiadiazolo[3,2‐a]pyrimidin‐7‐ones can be prepared by the acylation of 5‐amino‐1,3,4‐thiadiazoles with diketene and subsequent ring closure (dehydration). Whereas arylthio substituents (SC₆H₅) can be introduced in 2‐position by the replacement of Br, alkylthio groups (SC₂H₅) have to be already presentin the starting 5‐amino‐1,3,4‐thiadiazole. The ambident nucleophile 2‐thiazolidinethione reacts in the Br substitution reaction on the N atom.     

7‐Cyclopropyl‐2′‐deoxytubercidin: a carbocyclic side‐chain derivative of 7‐deaza‐2′‐deoxyadenosine

The title compound {systematic name: 4‐amino‐5‐cyclopropyl‐7‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐7H‐pyrrolo[2,3‐d]pyrimidine}, C₁₄H₁₈N₄O₃, exhibits an anti glycosylic bond conformation, with the torsion angle χ = −108.7 (2)°. The furanose group shows a twisted C1′‐exo sugar pucker (S‐type), with P = 120.0 (2)° and τ_m = 40.4 (1)°. The orientation of the exocyclic C4′—C5′ bond is ‐ap (trans), with the torsion angle γ = −167.1 (2)°. The cyclopropyl substituent points away from the nucleobase (anti orientation). Within the three‐dimensional extended crystal structure, the individual molecules are stacked and arranged into layers, which are highly ordered and stabilized by hydrogen bonding. The O atom of the exocyclic 5′‐hydroxy group of the sugar residue acts as an acceptor, forming a bifurcated hydrogen bond to the amino groups of two different neighbouring molecules. By this means, four neighbouring molecules form a rhomboidal arrangement of two bifurcated hydrogen bonds involving two amino groups and two O5′ atoms of the sugar residues.     

2′‐Deoxy‐7‐propynyl‐7‐deaza­adenosine: a DNA duplex‐stabilizing nucleoside

In the title compound, 2′‐deoxy‐7‐propynyl‐7‐deaza­adenosine, C₁₄H₁₆N₄O₃, the torsion angle of the N‐glycosylic bond is anti [χ = −130.7 (2)°]. The sugar pucker of the 2′‐deoxy­ribo­furanosyl moiety is C2′‐endo–C3′‐exo, ²T₃ (S‐type), with P = 185.9 (2)° and τ_m = 39.1 (1)°, and the orientation of the exocyclic C4′—C5′ bond is −ap (trans). The 7‐substituted propynyl group is nearly coplanar with the heterocyclic base moiety. Mol­ecules of the nucleoside form a layered network in which the heterocyclic bases are stacked head‐to‐tail with a closest distance of 3.197 (1) Å. The crystal structure of the nucleoside is stabilized by three inter­molecular hydrogen bonds of types N—H⋯ O, O—H⋯ N and O—H⋯ O.     

7‐Deaza‐2,8‐diaza­adenosine

In the title compound [systematic name: 4‐amino‐7‐(β‐d ‐ribofuranos­yl)‐7H‐pyrazolo[3,4‐d][1,2,3]triazine], C₉H₁₂N₆O₄, the torsion angle of the N‐glycosylic bond is high anti [χ = −83.2 (3)°]. The ribofuran­ose moiety adopts the C2′‐endo–C1′‐exo (²T₁) sugar conformation (S‐type sugar pucker), with P = 152.4° and τ_m = 35.0°. The conformation at the C4′—C5′ bond is +sc (gauche,gauche), with the torsion angle γ = 52.0 (3)°. The compound forms a three‐dimensional network that is stabilized by several hydrogen bonds (N—H⋯O, O—H⋯N and O—H⋯O).     

Synthesis of 2,4‐disubstituted 6‐phenyl‐7H‐pyrrolo[3,2‐d]‐pyrimidin‐7‐one 5‐oxides

A relatively short and efficient method for the utilization of 4,6‐dichloro‐2‐methylthio‐5‐nitropyrimidine ( 1 ) in the synthesis of the poly substituted pyrrolo[3,2‐d]pyrimidin‐7‐one 5‐oxides ( 6a ‐g) is reported. Some new 4‐substituted 6‐chloro‐2‐methylthio‐5‐nitropyrimidines ( 2a‐e ) were prepared by reaction of 4,6‐dichloro‐2‐methylthio‐5‐nitropyrimidine ( 1 ) with amines. 4‐Substituted 2‐methylthio‐5‐nitro‐6‐phenylethynylpyrimidines ( 3a‐e ), obtained from 4‐substituted 6‐chloro‐2‐methylthio‐5‐nitropyrimidines ( 2a‐e ) via palladium‐catalyzed Sonagashira coupling reaction with 1‐phenylacetylene, underwent smooth cyclization reaction in boiling 2‐propanol in the presence of catalytic amount of pyridine to give 4‐substituted 2‐methylthio‐6‐phenyl‐7H‐pyrrolo[3,2‐d]pyrimidin‐7‐one 5‐oxides ( 4a‐e ). The methylthio group of the latter compounds can be easily and selectively oxidized by m‐chloroperbenzoic acid and replaced with different amines.     

7‐Bromo­quinolin‐8‐ol

Structure analysis of the title compound, C₉H₆BrNO, has established that bromination of an 8‐hydroxyquinoline derivative occurred in the 7‐position. Intermolecular and weak intramolecular O—H⃛N hydrogen bonds are present, the former causing the mol­ecules to pack as hydrogen‐bonded dimers in the solid state.     

7‐Deaza‐2′‐deoxy­guanosine

In the title compound, 2‐amino‐7‐(2‐deoxy‐β‐d ‐erythro‐pentofuran­osyl)‐3,7‐dihydro­pyrrolo[2,3‐d]pyrimidin‐4‐one, C₁₁H₁₄N₄O₄, the N‐glycosylic bond torsion angle, χ, is anti [−106.5 (3)°]. The 2′‐deoxy­ribofuran­osyl moiety adopts the ³T₄ (N‐type) conformation, with P = 39.1° and τ_m = 40.3°. The conformation around the exocyclic C—C bond is ap (trans), with a torsion angle, γ, of −173.8 (3)°. The nucleoside forms a hydrogen‐bonded network, leading to a close‐packed multiple‐layer structure with a head‐to‐head arrangement of the bases. The nucleobase interplanar O=C—C⋯NH₂ distance is 3.441 (1) Å.     

Preparation of 2‐amino‐5‐methyl‐7H‐1,3,4‐thiadiazolo[3,2‐α]pyrimidin‐7‐ones

2‐Amino substituted 7H‐1,3,4‐thiadiazolo[3,2‐α]pyrimidin‐7‐ones 11a‐e were prepared by the reaction of 2‐bromo‐5‐amino‐1,3,4‐thiadiazole ( 1b ) and diketene ( 8 ), subsequent cyclocondensation ( 9b → 3b ) and displacement of the bromo substituents by the reaction with primary or secondary amines ( 3b → 11a‐e ). The hydrogen atom 6‐H in the heterobicycle 3b is replaced by a Cl or Br atom in the transformation of 3b → 14a,b. The 2‐bromo‐6‐chloro compound 14a reacts chemoselectively in the 2‐position with dimethylamine ( 14a → 15 ). The structure elucidations are based on one‐ and two‐dimensional NMR techniques including a heteronuclear NOE measurement.     

2‐Amino‐7‐chloro‐2′‐deoxy­tubercidin

In 4‐chloro‐7‐(2‐de­oxy‐β‐d ‐erythro‐pento­furanos­yl)‐7H‐pyr­rolo­[2,3‐d]­pyrimidine‐2,4‐diamine, C₁₁H₁₄ClN₅O₃, the conformation of the N‐glycosylic bond is between anti and high‐anti [χ = −102.5 (6)°]. The 2′‐deoxy­ribofuranosyl unit adopts the C3′‐endo‐C4′‐exo (³T₄) sugar pucker (N‐type) with P = 19.6° and τ_m = 32.9° [terminology: Saenger (1989). Landolt‐Börnstein New Series, Vol. 1, Nucleic Acids, Subvol. a, edited by O. Madelung, pp. 1–21. Berlin: Springer‐Verlag]. The orientation of the exocyclic C4′—C5′ bond is +ap (trans) with a torsion angle γ = 171.5 (4)°. The compound forms a three‐dimensional network that is stabilized by four inter­molecular hydrogen bonds (N—H⋯O and O—H⋯N) and one intra­molecular hydrogen bond (N—H⋯Cl).     

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).