Central Ring System Research Articles

Spectrophotometric Methods for the Determination of Fluoroquinolones: A Review

The majority of quinolones of clinical use belong to the subset of fluoroquinolones, which have a fluoro group attached the central ring system, typically at the 6-position. Fluoroquinolones are widely used in human and veterinary medicine. In recent times there has been significant development in the field of fluoroquinolones and many new analogues have been synthesized. The clinical and pharmaceutical analysis of these drugs requires effective analytical procedures for quality control and pharmacodynamic and pharmacokinetic studies. In this review article, various spectrophotometric methods used for determination of fluoroquinolones have been covered. The methods include visible spectrophotometry, which is based on formation of ion-pair or charge transfer complexes, UV spectrophotometry and derivative spectrophotometry. The application of these methods for the determination of fluoroquinolones in pharmaceutical and real samples has also been discussed.

3-(4-Chlorophenyl)-2-(2,4-dichlorophenoxy)-5-methyl-8,9,10,11-tetrahydro-2-benzothieno[2′,3′:2,3]pyrido[4,5-d]pyrimidin-4(3H)-one dichloromethane solvate

In the structure of the title compound, C26H18Cl3N3O2S·CH2Cl2, the C—S bond lengths in the thio­phene ring [1.733 (5) and 1.735 (5) A] are equivalent and long compared with the values observed in both free thio­phene, measured using electron diffraction, and thieno[2,3-c]pyridine. The central thienopyridine ring system is planar. The pyrimidinone ring forms a dihedral angle of 3.1 (2)° with the pyridine ring. The chloro- and dichloro­phenyl rings form dihedral angles of 75.2 (2) and 85.5 (2)°, respectively, with the pyrimidinone ring. The dihedral angle between the chloro­phenyl rings is 69.7 (2)°. The cyclo­hexene ring adopts a half-chair conformation. There is a C—H—O hydrogen bond between the main mol­ecule and the dichoromethane mol­ecule. The dichloro­methane mol­ecule is disordered over two positions, with refined occupancies of 0.775 (6) and 0.225 (6).

3-Butyl-2-(piperidin-1-yl)-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-one

In the title compound, C19H27N3OS, the central thienopyrimidine ring system is essentially planar. The cyclohexene ring adopts a half-chair conformation, while the piperidine ring is in a standard chair conformation. There is an intramolecular C—H...O hydrogen bond, which stabilizes the molecular structure. The crystal packing is stabilized by C—H...π interactions.

Total synthesis of heliannuol B, an allelochemical from Helianthus annuus

A total synthesis of the allelochemical heliannuol B 1 is described employing ring closing metathesis to generate the central benzoxepane ring system.

Biologically Active Natural Products from Mongolian Medicinal Plants Scorzonera divaricata and Scorzonera pseudodivaricata

Chromatographic separation of a crude extract obtained from the aerial parts of the Mongolian medicinal plant Scorzonera divaricata yielded the two new quinic acid derivatives feruloylpodospermic acids A and B. Both compounds feature a feruloyl group and two dihydrocaffeoyl substituents. For feruloylpodospermic acid A, the dihydrocaffeic acid substituents were found esterified at positions 1 and 5 of the quinic acid moiety, while the feruloyl group was attached at position 3. For feruloylpodospermic acid B, the substituents were linked at positions 1, 3, and 4. The aerial parts of S. pseudodivaricata that are likewise used in Mongolian traditional medicine yielded two further new natural products, for which the names scorzoneric acid and scorzonerin are proposed. Scorzoneric acid is an unusual phenolic compound featuring a central tetrasubstituted phenyl ring to which a glucose unit is bound, which in turn is substituted by an esterified acyl side chain. Further substituents of the central phenyl ring system include a butan-2-one group, which is linked to a second para-substituted phenyl ring system. Scorzonerin is a matricarin-based sesquiterpene lactone that carries an esterified dihydrocoumaric acid moiety, which in turn is glycosidically bound to glucose. The structures of all new compounds were unambiguously established from NMR (1H, 13C, COSY, HMBC) spectroscopic and mass spectrometric data. The new quinic acid derivatives feruloylpodospermic acids A and B exhibited strong antioxidative activity when analyzed in the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay.

Ethyl (4-oxo-1-phenyl-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-yl)acetate

Geometric parameters of the title compound, C14H12N4O3, a pyrazolopyrimidine derivative, are in the usual ranges. The dihedral angle between the pyrazolopyrimidine system and the phenyl ring is 4.64 (5)°. The non-H atoms of the ester side chain lie in a common plane (r.m.s. deviation = 0.028 Å) and this plane is almost perpendicular [77.69 (4)°] to the central ring system.

Methyl (4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-5-yl)acetate

The title compound, C14H12N4O3, a pyrazolopyrimidine derivative, displays normal geometrical parameters. The dihedral angle between the mean planes of the pyrazolopyrimidine unit and the phenyl ring is 26.14 (4)°. The non-H atoms of the ester side chain are coplanar (r.m.s. deviation = 0.009 Å) and this plane is almost perpendicular [dihedral angle = 84.31 (4)°] to the central ring system.

Ethyl 3-amino-6-phenyl-4-tolylfuro[2,3-b]pyridine-2-carboxylate

In the title compound, C23H20N2O3, the central furopyridine ring system is planar with an r.m.s deviation of 0.026 A. The terminal ethyl carboxyl­ate group is coplanar with the fused ring system. There is a short intra­molecular N—H⋯O hydrogen bond. C—H⋯π and π–π stacking inter­actions contribute strongly to the stability of the structure.

2,3-Bis[(1-phenyl-1H-tetrazol-5-ylsulfanyl)methyl]quinoxaline

The title compound, C24H18N10S2, crystallizes with two independent molecules in the asymmetric unit. The two terminal (1-phenyltetrazol-5-yl)sulfanyl groups adopt a trans configuration with respect to the central quinoxaline ring system in both independent molecules.

N-Allyl-4,6-bis(diphenylphosphino)phenoxazine-10-carboxamide

In the title compound, C40H32N2O2P2, used as a nixantphos-type ligand in homogeneous catalysis, the central phenoxazine ring system deviates markedly from planarity, the dihedral angle between the two halves being 38.14 (3)°. The intramolecular P...P distance is 4.2400 (7) Å.

Methyl 3-[4,6-bis(diphenylphosphino)phenoxazin-10-yl]propionate

In the title compound, C40H33NO3P2, used as a nixantphos-type ligand in homogeneous catalysis, the central phenoxazine ring system is nearly planar. The most important feature of the molecule is the intramolecular P...P distance of 4.2346 (13) Å. The angles involving the P atoms are in the range 100.90 (13)–103.40 (16)°.

Structure–Function Relation of Efomycines, a Family of Small-Molecule Inhibitors of Selectin Functions

Selectin-mediated leukocyte adhesion to endothelia, the crucial first step initiating the pathogenic cascade of inflammation, is an attractive target for specific therapies. The small-molecule macrolide, efomycine M, inhibits selectin-mediated leukocyte adhesion in vitro and in vivo, and effectively alleviates inflammatory disorders in vivo. To define the molecular basis of the therapeutically relevant antiadhesive properties of efomycines, several new species of this family were purified and/or synthesized. Efomycines E and G were isolated from Steptomyces BS1261. Efomycine O was synthesized by Lewis acid-catalyzed acetalization and efomycine M was generated by base-catalyzed deglycosylation. Efomycine S resulted from ester cleavage of the macrolide ring system, and efomycine T represents the peracetylated form of efomycine M. When the functional activity of efomycines on adhesion of leukocytes to vascular endothelium was studied, some remarkable differences between the compounds became apparent, inasmuch as efomycines E, G, M, and O significantly inhibited adhesion of both human and porcine leukocytes to the vascular endothelium, whereas efomycines S and T did not show any biological activity. A novel docking engine (ProPose), generating an improved, fully configurable protein-ligand interaction model, demonstrated that biological activities of efomycines can be predicted in silico, thus highlighting the utility of such combinatorial approaches.

1,6-Bis(4-chlorophenyl)-8-(4-pyridyl)-3,4-dihydropyrrolo[1,2-a]pyrazine

In the crystal struture of the title compound, C24H17Cl2N3, the two benzene rings and the pyridyl group lie in a propeller arrangement around the central ring system, thereby minimizing steric effects among these rings.

Synthesis of Alkyne-Bridged Cyclic Tripeptides toward Constrained Mimics of Vancomycin

The synthesis of a range of highly constrained cyclic tripeptides has been performed using either an intramolecular Sonogashira coupling or a macrolactamization as the final ring-closing reaction. Our approach gives access to rigidified 15-membered peptidic macrocycles based on the central ring system of vancomycin. Tripeptides 3a-c and dipeptide 11 were cyclized via an intramolecular Sonogashira reaction, and the cyclic peptides 4a-c and 15a were obtained in 6-23% yield. In contrast, macrolactamization of 12 and 17 resulted in the desired peptidic macrocycles 15b and 18 with 54-61% yield. Modeling studies hint at a distorted triple bond, which explains the low yield of the Sonogashira-based cyclization. Moreover, modeling data also showed that this class of peptidic macrocycles formed a cavity-like structure in which guest molecules may bind.

2,3-Bis(1-methyl-1H-imidazol-2-ylsulfanylmethyl)quinoxaline

The two terminal 1-methyl­imidazol-2-ylsulfanyl groups adopt a syn conformation with respect to the central quinoxaline ring system in the title compound, C18H18N6S2.

1,4-Bis(imidazol-1-ylmethyl)naphthalene

In the title compound, C18H16N4, the two imidazole rings are twisted away from the central naphthalene ring system by 81.4 (1) and 88.4 (1)°. The crystal packing is stabilized by C—H⋯N hydrogen bonds

The Asymmetric Total Synthesis of Nakadomarin A, a Marine Manzamine Alkaloid

AbstractFor Abstract see ChemInform Abstract in Full Text.

海洋産マンザミンアルカロイドナカドマリンＡの不斉全合成

Manzamine alkaloid, (-) -nakadomarin A (1) was first isolated from the Okinawan marine sponge in 1997. Its structure consists of an unprecedented hexacyclic ring system (8/5/5/5/15/6) that includes a furan ring. We report here the first total synthesis of both enantiomers of nakadomarin A.The spiro-lactam 29, obtained from methyl 4-oxopiperidine carboxylate, was coupled with a furan ring by Suzuki-Miyaura reaction to give intermediate 30. Intramolecular cyclization of the furan ring to acyliminium cation afforded the central core of nakadomarin A, 32. Both 8- and 15-membered rings were constructed by ring closing metathesis (RCM) to give dioxonakadomarin A, 14 which was reduced to (±) -1. Using chiral 23, obtained by optical resolution, the asymmetric synthesis of unnatural enantiomer, (+) -1 has been accomplished and the synthesis confirmed the absolute stereochemistry of (-) -1.A central ABD ring system 52, which has all stereocenters of (-) -1, was synthesized from chiral hydroisoquinolinone 49, derived from Diels-Alder reaction of chiral piperidinone 47 and siloxydiene 48. The intermediate 52 was converted to natural (-) -nakadomarin A by furan formation via endoperoxides followed by RCM.

Synthesis and biological activity of 22-oxa CD-ring modified analogues of 1α,25-dihydroxyvitamin D 3: spiro[5.5]undecane CF-ring analogues

The synthesis and biological activity of novel CD-ring modified analogues of 22-oxa-1α,25-dihydroxyvitamin D 3, lacking the D-ring and featuring a connection between C-18 and C-21 (spiro[5.5]undecane CF-ring analogues), is described. The central ring system is conveniently synthesised from an achiral intermediate. The analogues have marginal binding affinity for the nVDR and possess low to moderate genomic activity.

Chiral banana liquid crystals derived from sugars

This paper describes the synthesis and physical properties of a chiral bent-core liquid crystal containing the chiral non-aromatic central ring system 1,5-anhydro-2-desoxy-D-arabino-hexitol. The preparation involved a stepwise construction of the mesogenic side chains via a selective diesterification of glucal at positions three and six with 4-O-acetylbenzoyl chloride followed by selective deacetylation. Repeated esterification of the aromatic hydroxy group with a substituted benzoic acid and hydrogenation of the double bond resulted in the desired product. To our knowledge, this is the first banana shaped liquid crystal synthesized containing a sugar derivative as a chiral core. Investigation of the mesogenic properties and electro-optic experiments showed traditional calamitic phases along with banana phases.