5'-Substituted 2,2'-anhydrouridines

3',5'-Di-O-acetyl-2'-halogenouridines (1a, 1c and 1d) can be partially deacetylated at C-5' by transesterification with methanol-HCl, providing the 3'-O-acetyl derivatives 2a–2c. These can be converted into the 5'-O-mesyl derivatives 3a–3c, and latter into the 5'-chloro compounds 3d-3f. All 5'-substituted 2'-halogeno compounds give the corresponding 2,2'-anhydrouridine derivatives 4a–4c on treatment with NaOMe. Structures were proved by IR and ¹H-NMR.     

Photochemical cyclisation of 2',3'-0-isopropylidene-8-phenylthioadenosine to the 8,5'(R)- and 8,5'(S)-cycloadenosines (nucleosides and nucleoti

Photo-irradiation of 2',3-0-isopropylidene-8-phenylthioadenosine in the presence of the peroxides afforded the 8,5'-cyclonucleosides, which, after deacetonation, gave 8,5'(S)- and 8,5'(R)-cycloadenosine, the anti-type fixed model of adenosine. The absolute configurations of the 5'-carbon in these nucleosides were determined by NMR measurements.     

Synthesis of licoflavone-a and 6',6'-dimethylpyrano(2',3':7,8)flavone

Licoflavone-A assigned structure of 6-C-prenyl-7,4'-dihydroxyflavone 5 has been synthesized by condensing 5-C-prenyl-2-hydroxy-4-prenyloxyacetophenone 2 with p-prenyloxybenzaldehyde in the presence of alkali. The resulting chalcone 3 on cyclodehydrogenation with DDQ gave 6-C-prenyl-7,4'-diprenyloxyflavone 4 which on boiling with aqueous morpholine afforded the natural product. This synthesis uses, for the first time, protection of phenolic hydroxyls by O-prenylation and DDQ for conversion of chalcone to flavone. 6',6'-Dimethylpyrano (2',3':7,8)navone 8 has been synthesized by the Hlubucek reaction of 7-hydroxyflavone 6 with 2-chloro-2-methyl-3-butyne.     

A novel synthesis of 2'-hydroxy-1',3'-xylyl crown ethers

Six novel 2' - hydroxy - 1',3' - xylyl crown ethers (8a–e and 13)¹ have been synthesized utilizing the allyl group to protect the OH function during the cyclization reaction. The macrocycles 6a-e were formed in yields of 26 to 52%, by intermolecular reaction of 4 - chloro - 2,6 - bis(bromomethyl) - 1 - (2 - propenyloxy)benzene (5) with polyethylene glycols; 6a was also obtained by an intramolecular cyclization reaction of monotosylate 14.A 30-membered ring with a 2' - hydroxy - 1',3' - xylyl sub-unit was obtained in 87% yield by reaction of ditosylate 9 with bis [2 - (o - hydroxyphenoxy)ethyl]ether (11) in the presence of cesium fluoride. The synthesis of crown ethers with a 2' - hydroxy - 1',3' - xylyl sub-unit (1c–e, H for CH₃) by demethylation of the corresponding 2'-methoxy crown ethers 1c–e with lithium iodide were unsuccessful; it would appear that the demethylation reaction is restricted to 15- and 18-membered rings. One of the 2' - hydroxy - 1',3' - xylyl crown ethers 8d forms a crystalline 1:1-complex with water.     

2'-Desoxytubercidin: synthese des o-3'-phosphoramidites und kondensation zu 2'-desoxytubercidylyl(3' → 5')-2'-desoxytubercidin

The phosphoramidite of 2'-deoxytubercidin (2) has been prepared by phosphitylation of compound 3b with chlorodiisopropylaminomethoxyphosphane. The intermediate 3b was obtained from 2'-deoxytubercidin (1) by N⁴-benzoylation and subsequent O-5'-dimethoxytritylation. Condensation of compound 2 with O-3'-silylated 3e gave the fully protected dimer 4b, which was converted into 2'-deoxytubercidylyl (3' → 5')-2'-deoxytubercidin(4a). Compound 4a isoster with 2'-deoxyadenosylyl(3' → 5')-2'-deoxyadenosine (d(ApA)) exhibits a hypochromicity of 11% (270 nm) due to strong stacking interactions. Cleavage of the dinucleoside monophosphate 4a with nuclease S₁ occurs five times faster than that of d(ApA). This shows that the single strand specific enzyme recognises the geometry of the stacked nucleobases.     

The synthesis and crystal structure of 5-acetyl-2'-deoxyuridine

5- Acetyl - 2' - deoxyuridine (1) has been synthesised by treating 2' - deoxy - 5 - ethynyluridine with dilute sulphuric acid. Condensation of the trimethylsilyl derivative of 5-acetyluracil with 2-deox-3, 5-di-O-p-toluoyl-α-d-erythropen chloride gave a mixture of α- and β-anomeric blocked nucleosides from which the α-anomer was isolated and the p-toluoyl groups removed to give 5 - acetyl -1 - (α - d - 2- deoxyerythropentofuranosyl) uracil. Only a poor yield of the β-anomer (1) was obtained by this procedure. The UV spectra and m.p. obtained for 1 differed from the values quoted in the literature. The crystals of 1 are monoclinic, space group P2₁, with a = 9.525, b = 12.16, c = 5.22 Å, β = 92.03° and two molecules in the unit cell. The structure was refined by least-squares calculations to R 3.4% for 1426 observed counter amplitudes. The pyrimidine ring is essentially planar with the acetyl group inclined at 6° to it. The sugar ring has the highly unusual C(4')-exo conformation and the arrangement about C(4')-C(5') is such that O(5') is oriented gauche with respect to both O(1') and C(3'). The glycosidic torsion angle O(1')-C(1')-N(1)-C(6) is 56° (anti conformation).     

Aminophosphordichloridite: A new phosphorylating reagent for one-pot synthesis of 3'-5'- or 2'-5'-linked diribonucleotide having defined sequence

3'-5'- or 2'-5'-linked diribonucleotides having definite sequences have been synthesized by an one-flask procedure utilizing the cyclic phosphorylation of the cis-glycol in the ribonucleosides with aminophosphordichloridites.     

Synthesis of carbon-bridged 8,5'-cyclopurine nucleosides: Nucleosides and nucleotides—XXIV1

Treatment of 2',3'-O-isopropylidene-5'-deoxy-8,5'-cycloadenosine with selenium oxide afforded the 5'-oxo-compound. Reduction of the product with sodium borohydride proceeded stereoselectively to give the 8,5'(S)-cycloadenosine. The 5'-R-isomer was obtained by the inversion of the 5'-OH group of the S-epimer via the mesyloxy derivative. Hydrolytic deamination of 8,5'-cycloadenosines gave the inosine counterparts. Photo-irradiation of 2',3'-O-isopropylidene-5'-deoxy-5'-phenylthio-N²-benzoylguanosine afforded the 8,5'-cyclo-5'-deoxyguanosine, which was also converted to the 5'-oxo-derivative. Reduction of the product also afforded to give the 8,5'-(S)-cycloguanosine. The CD spectra of these cyclonucleosides reflect the chiralities at the 5'-position.     

Approche de la synthese d'anthracyclines oligosaccharidiques. Hemisynthese de la 4'-o-(2-desoxy l-fucosyl) daunorubicine

The preparation of the disaccharide 4 - O - (3,4 - di - O - acetyl - 2,6 - dideoxy - α - l - lyxo - hexopyranosyl) - 2, 3,6 - trideoxy - 3 - trifluoroacetamido - l - lyxo - hexopyranose, 11c, the N,N' - dimethyl derivative of which occurs naturally in numerous anthracyclines, is described. Glycosidation with daunomycinone followed by removal of the protecting groups led to 4' - O - (2 - deoxy - l - fucosyl) daunorubicine.     

Structural study of tropane-3-spiro-4'-imidazol-5'-one

Tropane-3-spiro-4'-imidazol-5'-one has been synthesized and its crystal and molecular structures determined by X-ray diffraction, IR, Raman, ¹H-NMR and ¹³C-NMR methods. The tautomeric equilibrium between this structure and the corresponding conjugated form in different solvents is also studied from IR and UV data. The imidazoline ring, the spiranic C(3, 4'), the N(8) and the methyl C(9) atoms are situated in a plane. The piperidine ring adopts a distorted chair conformation in the crystalline form and in solution. The flattening of the C(1), C(2), C(3, 4'), C(4), C(5) part of the chair and the opposite puckering are noticeably large. In order to complete the results, some spectroscopic measurements have also been made for the tropane-3-spiro-4'-imidazol-5'-one hydrochloride.     

Lithiation of 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)-2'-deoxyuridine: synthesis of 6-substituted 2'-deoxyuridines

Synthesis of 6-substituted 2'-deoxyuridines can be effected by lithiation of 3',5'-$\text{O}$-(tetraisopropyldisiloxane-1,3-diyl)-2'-deoxyuridine with LDA followed by the reaction of its lithio derivative with electrophiles. This method provides a general, regiospecific and simple route to various types of 6-substituted 2'-deoxyuridines which have, so far, been known to be difficult to prepare.     

Conformational analysis of 2', 3' and 4'-azachalcones by molecular orbital calculations

The semi-empirical quantum chemical PCILO method is used to perform a detailed conformational analysis of 2'-, 3'-and 4'-azachalcones. Several energy minima are obtained for each compound. Global energy minima (most stable conformations) are found for antiperiplanar-s-cis 2'-azachalcone, synperiplanar-s-cis 3'-azachalcone and s-cis 4'-azachalcone. The calculated results are compared with available experimental data.     

Preparation of oligoadenylates with 2'-5' linkage using Pb2+ ion catalyst

2'-5' Linked oligoadenylates up to a pentamer were formed selectively by Pb²⁺ ion-catalyzed polymerization of adenosine-5'-phosphorimidazolide in aqueous solution. Small amounts of oligoadenylate isomers containing both 2'-5' and 3'-5' internucleotide linkage were obtained simultaneously. The structure of the linkage isomers was established by sequential enzyme and alkaline digestion.     

11H-Pyrido[3',2':4,5]pyrrolo[2,3-g]isoquinoléines (aza-7 ellipticines) substituées sur leur position 6

6-Dialkylaminoalkylamino substituted 11H-pyrido[3',2':4,5]pyrrolo[2,3-g]isoquinolines (7-aza ellipti-cines) were obtained by a six step synthesis starting from 2-chloro-3-nitro pyridine and 6-amino-5-methyl (and 5,8-dimethyl) isoquinoline-1-2H-ones already described. A brief survey of biological results shows that derivatives of this new heterocyclic ring system are less interesting than their 5H-pyrido(3',4':4,5]pyrrolo[2,3-g]isoquinolines (9-aza ellipticines) and pyrido[4,3-b]carbazoles (ellipticines) analogues.     

Microbiological transformations—XII: Microbiological reduction of racemic 1-(2',2',3'-trimethyl-cyclopent-3'-en-1'-yl)propan-2-one and 1-(2',2',3'-trimethyl-cyclopent-3'-en-1'-yl)butan-2-one by rhodotorula mucilaginosa

The microbiological reduction of (±)-l-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-one (4) and (±)-1-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-butan-2-one (5) by Rhodotorula mucilaginosa was investigated. Both enantiomers of 4 are reduced stereospecifically to corresponding alcohols; (+)-(2S, l'R)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-ol (6) and (-)-(2S,l'S)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-ol (7). p ]The substrate selectivity in the reduction of 5 was observed: R enantiomer of 5 yields stereospecifically (+)-(2S,1'R)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-butan-2-ol (8) while S(-)5 remains unchanged.     

Practical synthesis of adenosine 3′,5′-cyclic monophosphorodithioate

Adenosine 3′,5′-cyclic monophosphorodithioate (cAMPS₂), which has two exocyclic sulfurs directly attached to phosphorus, was synthesized from adenosine phosphoramidite by intramolecular cyclization employing the phosphotriester method as a key step.     

Synthesis of some analogues of nucleoside 5′-triphosphates

Reaction of propane -1,3- disulphonyl chloride with the appropriate 5' - amino - 5'.- deoxyribonucleoside gave 5' - deoxy -5′-(3- sulphopropanesulpho5' - Deoxy - 5' - p- sulphaminobenzenesulphonylaminothymidine (8) was obtained by treatment of 5' - p- aminobenzenesulphonylamino - 5' -deoxythymidine (10) with SO₃,-triethylamine. This reaction gave also some 5'-p- aminobenzenesulphonylamino - 5' - deoxy - 3' - O - sulphothymidine (12). Compounds 2 and 3 were inactive when tested for inhibitory activity against E.coli RNA polymerase holoenzyme. Compounds 1 and 8 inhibited E.coli DNA polymerase I non-competitively at relatively high concentrations. Compound 4 was without significant inhibitory activity against HSV-1 DNA polymerase.     

Novel adsorptive materials by adenosine 5ʹ‐triphosphate imprinted‐polymer over the surface of polystyrene nanospheres for selective separation of adenosine 5ʹ‐triphosphate biomarker from urine

In this study, we have developed a method to assess adenosine 5?‐triphosphate by adsorptive extraction using surface adenosine 5′‐triphosphate‐imprinted polymer over polystyrene nanoparticles (412 ± 16 nm) for selective recognition/separation from urine. Molecularly imprinted polymer was synthesized by emulsion copolymerization reaction using adenosine 5′‐triphosphate as a template, functional monomers (methacrylic acid, N‐isopropyl acrylamide, and dimethylamino ethylmethacrylate) and a crosslinker, methylenebisacrylamide. The binding capacities of imprinted and non‐imprinted polymers were measured using high‐performance liquid chromatography with UV detection with a detection limit of 1.6 ± 0.02 µM of adenosine 5′‐triphosphate in the urine. High binding affinity (Q_MIP, 42.65 µmol/g), and high selectivity and specificity to adenosine 5′‐triphosphate compared to other competitive nucleotides including adenosine 5?‐diphosphate, adenosine 5?‐monophosphate, and analogs such as adenosine, adenine, uridine, uric acid, and creatinine were observed. The imprinting efficiency of imprinted polymer is 2.11 for urine (Q_MIP, 100.3 µmol/g) and 2.51 for synthetic urine (Q_MIP, 48.5 µmol/g). The extraction protocol was successfully applied to the direct extraction of adenosine 5′‐triphosphate from spiked human urine indicating that this synthesized molecularly imprinted polymer allowed adenosine 5′‐triphosphate to be preconcentrated while simultaneously interfering compounds were removed from the matrix. These submicron imprinted polymers over nano polystyrene spheres have a potential in the pharmaceutical industries and clinical analysis applications.     

Enthalpies de complexation de quelques phosphoramides avec le chlorure d'antimoine(V). Influence de la structure sur le nombre donneur selon Gutmann

Complexation enthalpies for various compounds with SbCl₅ have been calorimetrically determined in dilute dichloro-1,2 ethane solution at 25°C. In the case of 22 organo-phosphorylated compounds OPX_x,Y_3-x, (X, Y = NMe₂, Net₂, NHEt,

, OEt; x = 0, 1, 2, 3), our calorimetric results allow a characterization of Lewis basicity variations (as Gutmann's donor number DN) against the nature of substituents at the phosphorus atom. Within this scale, many compounds are more basic than HMPA OP(Nme₂)₃ whose DN is, according to our results, greater than currently admitted; if no systematic effects are noted, the influence of conformation may, however, explain the DN variations in each series (for X and Y given, x varying from 0 to 3). Moreover, thanks to conductometric measurements, an instantaneous reaction of triethylamine with the solvent is evidenced.     

Preferential formation of (2'–5')-linked internucleotide bonds in non-enzymatic reactions

The reactions of ImpU with MepU, MepC, MepA and MepG in aqueous solution yield mixtures of isomeric dinucleotides in which the (2'–5') linked compound is 6–9 times more abundant than the (3'–5')-linked compound. The ratio of isomers obtained from ImpA and MepA under these conditions is similar, but increases to 18 when a poly(U) template is included in the reaction mixture.