Synthesis of C-5 benzoyl and azido functionalized 2,2′-dithiobis-and 2,2′-diselenobis(1H-indoles)

Novel methods for the synthesis of C-5 benzoyl and azido analogues of 2,2′-dithiobis(1H-indole), 1, and 2,2′-diselenobis(1H-indole), 2, are described to further explore the structure activity relationships in this region of the molecule. Analogues 3-i displayed inhibitory activity (IC₅₀ = 0.45-2.03 μ) toward the catalytic domain of the epidermal growth factor receptor tyrosine kinase that was equivalent to or better than that of unsubstituted compounds 1 and 2. The regiochemistry of Friedel-Crafts benzoylation onto 1 was determined by X-ray crystallography. To test the potential for compounds of this class to interact with the epidermal growth factor receptor tyrosine kinase via a sulfhydryl exchange mechanism, reaction of a 2,2′-dithiobis(1H-indole) with glutathione was carried out and the product characterized.     

Reactions of 2,2′,5′,2′-terfuran

Formylation of 2,2′,5′,2′-terfuran ( 1 ) with N-methylformanilide and phosphorus oxychloride gave 5-formyl-2,2′,5′,2′-terfuran ( 2 ) and 5,5′-diformyl-2,2′5′,2′-terfuran ( 3 ). Reduction of 2 and 3 afforded 5-hydroxymethyl-2,2′,5′,2′-terfuran ( 4 ) and 5,5′ dihydroxymethyl-2,2′,5′,2′-terfuran ( 5 ), respectively. Terfuran 1 reacted with phenylmagnesium bromide to give 5-(phenylhydroxymethyl)-2,2′,5′,2′-terfuran ( 6 ), and was carbonated to 5-carboxy 2,2′,5′,2′-terfuran ( 7 ) and 5,5′-dicarboxy-2,2′,5′,2′-terfuran ( 8 ). Bromination of 1 with N-bromosuccinimide gave 5,5′-dibromo 2,2′,5′,2′-terfuran ( 9 ).     

Synthesis of 2,2′-bipyrimidine derivatives

A new total synthesis of 2,2′ -bipyrimidine derivatives by the direct condensation of 2-amidinopyrimidinebenzenesulfonate with dicarbonyl compounds is described. The following 2,2′-bipyrimidines have been prepared: 5-ethyl-4,6-dihydroxy-2,2′-bipyrimidine; 5-ethyl-4,6-dichloro-2,2 -bipyrimidine; 4,6-dihydroxy-2,2′ -bipyrimidine; 5-ethyl-4,6-dimethoxy-2,2′ -bipyrimidine.     

Mass spectral fragmentation pattern of 2,2′-bipyridyls. Part VIII. 2,2′-Bipyridyl-5-carboxylic Acid and 2,2′-bipyridyl-5-sulphonic acid

The mass spectra of 2,2′-bipyridyl-5-carboxylic acid and 2,2′-bipyridyl-5-sulphonic acid obtained by electron impact are described. The principal initial fragmentation routes from the molecular ion of the carboxylic acid involve loss of CO, CN^˙, HCN, CO₂, OH^˙ and H₂O. From the molecular ion of the sulphonic acid the principal fragmentations are accompanied by loss of HCN, O₃, SO₂ and SO₃.     

4′‐Iodo‐2,2′:6′,2′′‐terpyridine

In the nearly planar title compound, C₁₅H₁₀IN₃, the three pyridine rings exhibit transoid conformations about the interannular C—C bonds. Very weak C—H...N and C—H...I interactions link the molecules into ribbons. Significant π–π stacking between molecules from different ribbons completes a three‐dimensional framework of intermolecular interactions. Four different packing motifs are observed among the known structures of simple 4′‐substituted terpyridines.     

Synthesis and NMR characterization of 3,4′-dibutoxy-2,2′-bithiophene

3,4′-Dibromo-2,2′-bithiophene was converted, in high yield, into the corresponding dibutoxy derivative. The ¹H ¹³C and nmr data are discussed in comparison with those of 3,3′- and 4,4′-dibutoxy-2,2′-bithiophene in relation to regiochemistry.     

Synthesis of 2′-Deoxyisoguanosine 5′-Triphosphate and 2′-Deoxy-5-methylisocytidine 5′-Triphosphate

The syntheses of the 5′-triphosphates of 2′-deoxyisoguanosine (=p₃isoG_d) and 2′-deoxy-5-methylisocytidine (=p₃me⁵isoC_d), two new bases for the genetic alphabet, are described. The triphosphates were synthesized from the corresponding nucleosides using a transient-protection procedure. The introduction of a methyl group at the 5-position of 2′-deoxyisocytidine remarkably improved the stability of the triphosphate. Characterization of the triphosphates included enzymatic incorporation opposite the complementary base in a template oligonucleotide.     

4′‐Vinyl‐2,2′:6′,2′′‐ter­pyridine

The title compound, C₁₇H₁₃N₃, is a versatile precursor for polymeric ter­pyridine derivatives and their metal complexes. The mol­ecule has transoid and near‐coplanar pyridine rings. However, the vinyl group is forced out of the plane of the terpyridyl moiety by a close H?H contact.     

Synthesis of some 5-aryl-2,2′-dipyrromethenes as analogs of prodigiosin

Three new dipyrromethenes have been synthesized as analogs of prodigiosin: 3-methoxy-5-phenyl-2,2′-dipyrromethene (10a) , 3-methoxy-4 -pentyl-5-phenyl-5′-methyl-2,2′-dipyrromethene (10b) , and 3-methoxy-4′-pentyl-5′-methyl-5-(2″-thienyl)-2,2′-dipyrromethene (10c). The Michael addition of ethyl glycinate to an appropriate arylidenemalonate, quenched with ethyl chloroformate and followed by a Dieckmann cyclization gave diethyl 1-ethoxycarbonyl-3-oxo-5-phenyl and thienylpyrrolidine-2,4-dicarboxylate, 2a and 2b. Methylation of the highly enolic keto-esters, followed by oxidation to N-ethoxycarbonylpyrroles led, after appropriate elaboration of the pyrrole nucleus, to 2-phenyl- and 2-thienyl-4-methoxypyrroles. The acid catalyzed condensation of these arylmethoxypyrroles with either pyrrole-2-carboxaldehyde or 5-methyl-4-pentylpyrrole-2-carboxaldehyde led to 10a, 10b and 10c.     

2,2′-Disubstituted 5,5′-bipyrimidines

Syntheses of 2,2′-bis(methylthio)-, 2,2′-diamino-, 2,2′-dihydroxy-, 2,2′ -dichloro-, and 2,2′ -diethoxy-5,5;′-bipyrimidines are described.     

2,2′:6′,2″‐Terpyridines Functionalized with Thienyl Substituents: Synthesis and Applications

This review deals with the synthesis and applications of 2,2′:6′,2″‐terpyridines which are functionalized with thiophene ring, directly linked to the terpyridine core or via a spacer. Two main methodologies were used, ring closure of diketo‐derivatives and cross coupling reactions. The obtained compounds find applications in various fields especially in material sciences such as solar cells or macromolecular sciences.     

Colchicine models: Synthesis and Antitubulin Activity of 2′-Monosubstituted and 2′, 5-Disubstituted 2,3,4,4′-Tetramethoxy-1,1′-biphenyls. Synthesis of 4,4′, 5′, 6′-tetramethoxy-1,1′-biphenyl-2,3′-dicarboxylic acid

Reductive amination of 2,3,4,4′-tetramethoxtybiphenyl-2-carbaldehyde ( 4 ) with MeNH₂ afforded methylamine 5 (Scheme 1), Hydroxymethylation of amine 8 , prepared similarly from 4 by reductive amination with benzylamine followed by N-methylation, afforded alcohol 12 which was converted the 5-methyl-substituted methylamine 14 by conventional chemical reactions (Scheme 2), Methylamine 14 was also obtained from ester 16 after hydroxymethylation to alcohol 17 and conventional manipulation of alcohol and ester functions (Scheme 2). Both amines 5 and 14 as well as the 2′, 5-dimethyl-substituted biphenyl 26 prepared from the dialdehyde 25 by a Wolff-Kishner reduction, did not show noteworthy activity in the tubulin binding assay or as inhibitors of tubulin polymerization (Table). However, the 2′ethyl-substituted biphebyl 11 prepared from 4 by reaction with MeLi followed by dehyderation and catalytic reduction of styrene 10 (Scheme 1) showed appreciable activity in both assays, coming close to that of known phenyltropolone models. The X-ray analysis of 14 ·HCl and 11 showed significant difference in the orientation of the rings with respect to one another (Fig.).     

Mass spectral fragmentation pattern of 2,2′-Bipyridyls. Part IX. 6-Alkoxy-2,2′-bipyridyls

The mass spectral fragmentation patterns of 6-methoxy-, 6-ethoxy- and 6-propoxy-2,2 ′-bipyridyls are reported. The base peaks in the spectra of both the 6-methoxy and 6-ethoxy compounds are due to the M-lion of 6-methoxy-2,2′-bipyridyl, while the base peak with 6-propoxy-2,2- bipyridyl is due to a species formed by loss of C₃H₆ from the molecular ion.     

Mass spectral fragmentation pattern of 2,2′-bipyridyls. Part XIII. 6-Chloro- and 6-bromo-2,2′-bipyridyls

The mass spectra of 6-chloro- and 6-bromo-2,2′-bipyridyls are reported. The principal fragmentation route from the molecular ions involves loss of the halogen group to give the M-1 ion of 2,2′-bipyridyl which gives rise to the base peak in the spectra. Loss of HCN before loss of Cl occurs to a small extent with 6-chloro-2,2′-bipyridyl.     

Synthesis of various 5-substituted 2′-deoxy-3′-5′-di-O-acetyluridines

The Pd(0)-catalyzed coupling reaction of β-5-iodo-2′-deoxy-3′,5′-di-O-acetyluridine with various heteroaryltrimethylstannyl compounds gave the corresponding β-5-heteroaryl-2′-deoxy-3′,5′-di-O-acetyluridines in moderate yields. This direct coupling approach for nucleosides represented an interesting alternative to the 5-heteroaryl functionalization of pyrimidines followed by the Hilbert-Johnson glycosylation reaction which often yields mixtures of the α and β anomers.     

Mass spectral fragmentation pattern of 2,2′-bipyridyls. Part II. 5-Hydroxy- and 5-alkoxy-2,2′-bipyridyls

The mass spectra of 5-hydroxy-, 5-methoxy-, 5-ethoxy- and 5-propoxy-2,2′-bipyridyls are reported. The fragmentation proposals are supported by high resolution mass measurements and metastable transitions.