The influence of sulfur substituents on the molecular geometry and packing of thio derivatives of N‐methylphenobarbital

The room‐temperature crystal structures of four new thio derivatives of N‐methylphenobarbital [systematic name: 5‐ethyl‐1‐methyl‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trione], C₁₃H₁₄N₂O₃, are compared with the structure of the parent compound. The sulfur substituents in N‐methyl‐2‐thiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐2‐thioxo‐1,2‐dihydropyrimidine‐4,6(3H,5H)‐dione], C₁₃H₁₄N₂O₂S, N‐methyl‐4‐thiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐4‐thioxo‐3,4‐dihydropyrimidine‐2,6(1H,5H)‐dione], C₁₃H₁₄N₂O₂S, and N‐methyl‐2,4,6‐trithiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trithione], C₁₃H₁₄N₂S₃, preserve the heterocyclic ring puckering observed for N‐methylphenobarbital (a half‐chair conformation), whereas in N‐methyl‐2,4‐dithiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidine‐6(5H)‐one], C₁₃H₁₄N₂OS₂, significant flattening of the ring was detected. The number and positions of the sulfur substituents influence the packing and hydrogen‐bonding patterns of the derivatives. In the cases of the 2‐thio, 4‐thio and 2,4,6‐trithio derivatives, there is a preference for the formation of a ring motif of the R₂²(8) type, which is also a characteristic of N‐methylphenobarbital, whereas a C(6) chain forms in the 2,4‐dithio derivative. The preferences for hydrogen‐bond formation, which follow the sequence of acceptor position 4 > 2 > 6, confirm the differences in the nucleophilic properties of the C atoms of the heterocyclic ring and are consistent with the course of N‐methylphenobarbital thionation reactions.     

Semisynthesis of 3′(2′)‐O‐(Aminoacyl)‐tRNA Derivatives as Ribosomal Substrate

An efficient synthesis of (3′‐terminally) 3′(2′)‐O‐aminoacylated pCpA derivatives is described, which could lead to the production of (aminoacyl)‐tRNAs following T4 RNA ligase mediated ligation. The tetrahydrofuranyl (thf) group was used as a permanent protective group for the 2′‐OH of the cytidine moiety which can be removed during the purification of the 3′(2′)‐O‐aminoacylated‐pCpA. This approach allowed for a general synthesis of (3′‐terminally) 3′(2′)‐O‐aminoacylated oligonucleotides. The fully protected pCpA 14 was synthesized by phosphoramidite chemistry and treated with NH₃ solution to remove the 2‐cyanoethyl and benzoyl groups (→ 15 ; Schemes 1 and 2). The 2′‐O‐thf‐protected‐pCpA 15 was coupled with α‐amino acid cyanomethyl esters, and the products 20a – c were deprotected and purified with AcOH buffer to afford 3′(2′)‐O‐aminoacylated pCpA 21a – c in high yields. The 3′(2′)‐O‐aminoacylated pCpA were efficiently ligated with tRNA(? CA) to yield (aminoacyl)‐tRNA which was an active substrate for the ribosome.     

Nonglycoside analogs of nucleotides

N¹-(2′,3′-Dihydroxypropyl)uracil, -thymine, -cytosine, and N⁹-(2′,3′-dihydroxypropyl)adenine were synthesized by alkylation of nucleic bases with 2,3-O-isopropylideneglycerol chlorohydrin, subsequent separation of the resulting mixtures, and removal of the protective groupings. Phosphorylation of these compounds or of their selectively substituted derivatives gave 2′(3′)-monophosphates, which were converted to 2′,3′-cyclophosphates by reaction with N,N′-dicyclohexylcarbodiimide. Thionation of the corresponding cytosine derivatives gave N¹-(2′,3′-dihydroxypropyl)-4-thiouracil and its 2′(3′) phosphate.     

Synthesis and reduction of thieno[2′,3′(3′,2′ or 3′,4′):5,6]-azocino[2,1-a]isoindole-7, 13-diones

A synthesis of the thieno[2′,3′(3′,2′ or 3′,4′):5,6]azocino[2,1-a]isoindole-7,13-diones 6a-c was developed from N-thienylethylphthalimides 3a-c using a Wittig reaction followed by a Friedel-Crafts cyclization of acetic acid derivatives 5a-c . Reduction of ketones 6a-c into alcohols 7a-c was stereo specific.     

Dual substituent parameter analysis of the ethyl and ipso 13C n.m.r. chemical shifts of some ring-substituted ethylbenzenes and ethylnaphthalenes

The natural abundance ¹³C n.m.r. spectra of a series of para-substituted ethylbenzenes, 4-substituted-1-ethylnaphthalenes and a limited series of 6-substituted-2-ethylnaphthalenes have been examined at low dilution in deuterochloroform solvent. The ethyl carbons and C_ipso in the phenyl series (i.e. have been assigned, and substituent chemical shifts for these carbons calculated and analysed by the Dual Substituent Parameter treatment. (Chemical shifts of all ring carbons have been obtained, but not assigned). Generally speaking, electron-withdrawing substituents lead to positive (i.e. downfield) substituent chemical shifts for CH ₂ and negative substituent chemical shifts for C H₃, i.e. ‘normal’ and ‘inverse’ behaviour respectively. C_ipso in the phenyl series exhibits a ‘normal’ dependence. The dependences of the various substituent chemical shifts on inductive and resonance parameters are discussed, and compared with the behaviour of side chain carbons in other substituted benzene systems.     

Carbon-13 nuclear magnetic resonance study of a new ring-chain tautomerism of some pyridazine derivatives

The ¹³C NMR spectra of a number of pyridazine derivatives have been recorded in DMSO-d₆ solution and analysed. Examination of the most diagnostic resonances, with particular emphasis on those arising from the pyridazine ring system, enabled the ready establishment of the presence of a ring-chain tautomerism in 5-(o-aminophenylcarbamoyl)pyridazine-4-carboxylic acid, methyl 5-(o-aminophenylcarbamoyl)pyridazine-4-carboxylate, 5-(o-aminophenylcarbamoyl)-3,6,-dimethylpyridazine-4-carboxylic acid and 5-(2-amino-1,2-dicyanovinylenecarbamoyl)pyridazine-4-carboxylic acid. This gave rise to 3′,4′-dihydro-3′-oxospiro[pyridazine-5(2H),2′(1H)-quinoxaline]-4-carboxylic acid, methyl 3′,4′-dihydro-3′oxospiro[pyridazine-5(2H),2′(1′H)-quinoxaline]-4-carboxylate, 3′,4′-dihydro-3′-oxo-3,6-dimethylspiro[pyridazine-5(2H), 2′(1′H)-quinoxaline]-4-carboxylic acid and 5-oxo-2,3-dicyano-1,4,8,9-tetraazaspiro[5.5]undeca-2,7,10-triene-11-carboxylic acid, respectively.     

Group IV organometal derivatives of pyridine. I—A 1H and 13C NMR investigation of trialkylmetal derivatives of pyridine

The proton and carbon-13 NMR spectra of thirteen trialkylmetal derivatives of pyridine, several of which were previously unknown, have been recorded and analysed. The proton NMR spectra show variations in proton chemical shifts but not in proton-proton coupling constants when the metal substituent is changed; the ring proton-metal coupling constants ⁿJ(M? H) in the tin and lead derivatives correspond closely with the corresponding proton-proton couplings ⁿJ(H? H) in pyridine. The carbon-13 chemical shifts of the carbons bound to the metal can apparently be correlated with the electron-donating ability of the trialkylmetal group. In the trimethylstannylpyridines the value of ¹J(Sn? C_ring) varies greatly with the position of the Me₃Sn group.     

Novel Fluoride‐Labile Nucleobase‐Protecting Groups for the Synthesis of 3′(2′)‐O‐Aminoacylated RNA Sequences

With the aim to develop a general approach to a total synthesis of aminoacylated t‐RNAs and analogues, we describe the synthesis of stabilized, aminoacylated RNA fragments, which, upon ligation, could lead to aminoacylated t‐RNA structures. Novel RNA phosphoramidites with fluoride‐labile 2′‐O‐[(triisopropylsilyl)oxy]methyl (=tom) sugar‐protecting and N‐{{2‐[(triisopropylsilyl)oxy]benzyl}oxy}carbonyl (=tboc) base‐protecting groups were prepared (Schemes 4 and 5), as well as a solid support containing an immobilized N⁶‐tboc‐protected adenosine with an orthogonal (photolabile) 2′‐O‐[(S)‐1‐(2‐nitrophenyl)ethoxy]methyl (=(S)‐npeom) group (Scheme 6). From these building blocks, a hexameric oligoribonucleotide was prepared by automated synthesis under standard conditions (Scheme 7). After the detachment from the solid support, the resulting fully protected sequence 34 was aminoacylated with L ‐phenylalanine derivatives carrying photolabile N‐protecting groups (→ 42 and 43 ; Scheme 9). Upon removal of the fluoride‐labile sugar‐ and nucleobase‐protecting groups, the still stabilized, partially with the photolabile group protected precursors 44 and 45 , respectively, of an aminoacylated RNA sequence were obtained (Scheme 9 and Fig. 3). Photolysis of 45 under mild conditions resulted in the efficient formation of the 3′(2′)‐O‐aminoacylated RNA sequence 46 (Fig. 4). Additionally, we carried out model investigations concerning the stability of ester bonds of aminoacylated ribonucleotide derivatives under acidic conditions (Table) and established conditions for the purification and handling of 3′(2′)‐O‐aminoacylated RNA sequences and their stabilized precursors.     

Pteridine studies: III—13C n.m.r. data of pteridine,some of its derivatives and their covalent σ-adducts with ammonia and water

¹³C n.m.r. spectral data of pteridine and nineteen of its derivatives (containing one or more chloro, methylthio, methyl, t-butyl or phenyl substituents) are reported. The ¹³C n.m.r. spectrum of the title compound has been assigned conclusively. ¹³C n.m.r. substituent effects are shown to be very useful in discerning between 6- and 7-substituted pteridines. Additionally, the ¹³C n.m.r. spectra of several covalent amination products, i.e. the 3,4-dihydro-4- amino- and the 5,6,7,8-tetrahydro-6,7-diaminopteridine derivatives, formed by dissolving the appropriate pteridine in liquid ammonia, have been recorded. The ¹³C n.m.r. spectra of the corresponding covalent hydrates are also reported.     

Cyclometallated compounds of manganese(I) with 1-methylphenylimidazoles

Cyclometallated complexes of magnanese(I) with 1-methylphenylimidazoles have been prepared. IR and ¹H NMR spectroscopic studies show they are octahedral complexes in which the imidazole ligand is bound to the metal through the nitrogen and phenyl C(6) atoms. When the imidazole ligand with two phenyl groups at the C(2′) and C(4′) atoms is used, both possible cyclometallated compounds are obtained.     

Carotenoids of Rhizobia. I. New Carotenoids from Rhizobium lupini

The main pigments of Rhizobium lupini were 2,3,2′,3′-di-trans-tetrahydroxy-β,β-caroten-4-one and 2,3,2′,3′-di-trans-tetrahydroxy-β,β-carotene. As minor components 7,8,7′,8′-tetrahydro-ψ, ψ-carotene (ζ-carotene), β, β-carotene (β-carotene), and tentatively, a 2,3,2′(or 3′)-trihydroxy-β, β-caroten-4-one and a 2,3,2′(or 3′)-trihydroxy-β, β-carotene were identified.     

Palladium(II) and Platinum(II) Complexes of N-Phenyl- and N-Ethyl-N′-pyrimidin-2-ylthiourea

Palladium(II) and platinum(II) complexes of N-ethyl-N′-pyrimidin-2-ylthiourea(HL¹) and N-phenyl-N′-pyrimidin-2-ylthiourea (HL²) have been prepared, and the complexes [M(HL)Cl₂], [Pt(L)₂], [Pd(HL¹)₂]Cl₂, and [Pd(L²)₂] (where M = Pd^II or Pt^II) were characterized. The spectroscopic data are consistent with coordination of thioureas as neutral or monoanionic ligands to Pd^II and Pt^II through S and a pyrimidine-N. The IR spectra show shifts of CS and pyrimidine ring stretch bands to lower and higher frequencies, respectively. The ¹H NMR spectra differentiate between H(4′) and H(6′) resonances and indicate downfield shifts for all protons of pyrimidine [H(4′), H(5′), and H(6′)], two resonances for two N?H protons for complexes containing the neutral ligand (HL), and only one N?H proton chemical shift for complexes containing the monoanion (L). ¹³C NMR chemical shifts of pyrimidine carbons are correlated with the type of bonding between Pd^II or Pt^II and pyrimidine-N. The magnetic susceptibilities suggest a diamagnetic planar structure for all complexes.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

13C NMR spectra of non-labelled and 15N-mono-labelled azo dyes

¹³C NMR spectra of four types of azo coupling products from benzenediazonium chloride have been measured and interpreted, viz. hydrazo compounds with an intramolecular hydrogen bond (3-methyl-1-phenylpyrazole-4,5-dione 4-phenylhydrazone), azo compounds without an intramolecular hydrogen bond (4-hydroxyazobenzene), azo compounds with an intramolecular hydrogen bond (2-hydroxy-5-tert-butylazobenzene) and an equilibrium mixture of both the tautomers of 1-phenylazo-2-naphthol. The absolute values of the J(¹⁵N¹³C) coupling constants have been determined by recording the spectra of the ¹⁵N isotopomers, and have been used, in some cases, for ¹³C signal assignment. A relationship has been found between the chemical shifts of the C-1′ to C-4′ carbons of the phenyl group (from the benzenediazonium ion) or the ¹J(¹⁵N¹³C) coupling constant, and the composition of the tautomeric mixture.     

Synthesis of 4-(5-Nitrophenylfur-2-yl)-1,2,3-thia- and Selenadiazoles

Arylation of 2-acetylfuran with o-, m-, and p-nitrophenyldiazonium salts under the conditions of the Gomberg-Bachmann reaction has afforded the corresponding 5-(nitrophenyl)-2-acetylfurans. Their carbo-ethoxyhydrazones have undergone the cyclization into stable 4-(5-nitrophenylfur-2-yl)-1,2,3-thiadiazoles under the conditions of the Hurd-Mori reaction. Analogous semicarbazones have afforded the corresponding selenadiazoles upon oxidation with selenium dioxide. The analysis of electronic absorption spectra of the obtained hybrid heterocycles has shown that the conjugation of the phenyl and the furan ring in o-nitrophenyl derivatives is distorted due to steric hindrance, whereas the effect of direct polar conjugation leading to strong bathochromic shift of the absorption band has been observed in the case of the p-nitro derivatives. The position and intensity of the bands in the electronic absorption spectra of the studied compounds are determined by electronic as well as steric factors. The difference in the length of conjugation chain determined by the position of the nitro group in the phenyl fragment also contributes to the observed trend. The introduction of selenadiazole fragment instead of thiadiazole one has caused slight bathochromic shift of the band in the electron absorption spectra.

     

Synthesis and structural study of novel 5-aryl substituted 2-amino-4,7-dioxopyrido[2,3-d]pyrimidines

The tide compounds 4a-c have been prepared in a one-step procedure from 2,4-diamino-6-hydroxy-pyrimidine (1) and the corresponding arylidene substituted Meldrum's acids 2a-e in very good yields. Semiempirical theoretical calculations (AMI) reveal two favoured conformations ( A and B ) for compounds 4a-e. The ¹H-nmr determinations, by using Karplus and Altona equations, clearly indicate that conformation A, with the aryl group on C5 in a pseudoaxial position, is that predominant in solution. The calculated charge density values for the olefinic carbons are in agreement with the experimental push-pull effect observed in the ¹³C-nmr spectra.     

Hydroacridines: Part 23. 1H and 13C NMR spectra of sym‐octahydroacridine,its 9‐(3‐pyridyl) and 9‐(4‐pyridyl) derivatives and the corresponding N(10)‐oxides. An experimental approach to the diamagnetic anisotropy of the pyridine nucleus

The complete ¹H NMR chemical shift assignments of 1,2,3,4,5,6,7,8‐octahydroacridine ( 1 ), 1,2,3,4,5,6,7,8‐octahydro‐9‐(3‐pyridyl)acridine ( 2 ), 1,2,3,4,5,6,7,8‐octahydro‐9‐(4‐pyridyl)acridine ( 3 ) and the corresponding N(10)‐oxides 1a , 2a and 3a , respectively, were achieved on the basis of 400 MHz ¹H NMR spectra and proton–proton decoupling, HMQC and NOEDIFF experiments. The spectral data for the above compounds provided the first experimental evidence of the difference in the anisotropy effect of the two non‐symmetrical moieties of the pyridine nucleus, and allowed us to ascertain that the shielding effect of the moiety defined by the C(2′)—N—C(6′) atoms is weaker than that of the C(3′)—C(4′)—C(5′) moiety. The ¹³C NMR spectra of 1 – 3 and 1a – 3a and the effect of N(10)‐oxidation on the ¹³C NMR chemical shifts are also discussed. The N‐oxidation of 2 and 3 with m‐chloroperbenzoic acid occurred regiospecifically, affording the N(10)‐oxides 2a and 3a free of N(1′)‐oxide isomers. Copyright © 2002 John Wiley & Sons, Ltd.     

Die identifizierung und untersuchung von isomeren O-acylribonucleosiden mit hilfe des circulardichroismus

The CD spectra of benzoyl, p-nitrobenzoyl and anisoyl derivatives of adenosine, uridine, 1-methylriboside and 1-D-ribofuranosylbenzimidazole are registrated. The possibility of identification of 2′-, 3′-O-acylribonucleosides and observation of acyl groups isomerisation kinetics is shown. The kinetics of 2′?3′ migration of a number of 2′(3′)-O-derivatives, the dependence of kinetic constants on the pH are studied. The features of acyl derivated ribonucleosides CD spectra are discussed.     

A Simple Procedure for Selective Acylation of the Less Reactive Hydroxyl Functionality in Some Dihydroxylated Compounds

Abstract

Phenolic (3′) esters (acetate, N-t-Boc glycinate) of the (+) 3S, 4S 5′(1′,1′-dimethylheptyl)-7-hydroxy-δ⁶?tetrahydrocannabinol (dexanabinol) were synthesized via the 7′-trifluoroacetate followed by acylation and subsequent deprotection.     

Carbon-13 nuclear magnetic resonance spectra of some methyl and phenyl substituted 2H-azirines

Carbon-13 n.m.r. spectra have been obtained for some methyl and phenyl substituted 2H-azirines. The higher field resonance of C-2 than that of the corresponding aziridine carbon is interpreted in terms of ring strain. Substituent effects on the chemical shifts of the azirine ring carbons are discussed. A set of additivity parameters for the methyl and phenyl groups are obtained which can be used for the calculation of the chemical shifts of the azirine ring carbons. The substituent effect of an azirine ring on the chemical shift of benzene is also discussed in comparison with those of some other substituents. A high degree of s character (48.5%) in the exocyclic orbital of C-3 is indicated by a large J(¹³C-3,H) value (242.5 Hz).