A facile route to the synthesis of novel 2-amino-1,4,5,6-tetrahydropyrimidines from Baylis-Hillman products of acrylonitrile

A facile route for the synthesis of novel 5-substituted-2-amino-1,4,5,6-tetrahydro pyrimidines from the Baylis-Hillman adducts obtained from reaction of aldehydes and acrylonitrile is described.

Expeditious synthesis of 5,6,7 ,8-tetrahydro-imidazo[1,2-a ] pyrimidin-2-ones and 3,4,6,7 ,8,9-hexahydro-pyrimido[,2-a ] pyrimidin-2-ones

A convenient synthesis of new 5,6,7 ,8-tetrahydro-imidazo[ 1,2-a]pyrimidin-2-ones and 3,4,6,7 ,8,9-hexahydro-pyrimido[1 ,2a]pyrimidin-2- ones from the Baylis-Hillman adducts of acrylonitrile and their derivatives is described. A common strategy employed to achieve the syntheses of title compounds involved generation of diamines from different Baylis-Hillman derivatives followed by treatment with cyanogen bromide at reflux temperature to trigger a double intramolecular cyclization.

6,6 '-bis (5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo[1,2,4]triazin-3-yl) [2,2 ']bipyridine, an effective extracting agent for the separation of americium(III) and curium(III) from the lanthanides

The extraction of americium(III), curium(III), and the lanthanides(III) from nitric acid by 6,6'- bis (5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo[1,2,4]triazin-3-yl)-[2,2'] bipyridine (CyMe4-BTBP) has been studied. Since the extraction kinetics were slow, N,N'-dimethyl-N,N'-dioctyl-2-(2-hexyloxy-ethyl)malonamide (DMDOHEMA) was added as a phase transfer reagent. With a mixture of 0.01 M CyMe4-BTBP + 0.25 M DMDOHEMA in n -octanol, extraction equilibrium was reached within 5 min of mixing. At a nitric acid concentration of 1 M, an americium(III) distribution ratio of approx. 10 was achieved. Americium(III)/lanthanide(III) separation factors between 50 (dysprosium) and 1500 (lanthanum) were obtained. Whereas americium(III) and curium(III) were extracted as disolvates, the stoichiometries of the lanthanide(III) complexes were not identified unambiguously, owing to the presence of DMDOHEMA. In the absence of DMDOHEMA, both americium(III) and europium(III) were extracted as disolvates. Back-extraction with 0.1 M nitric acid was thermodynamically possible but rather slow. Using a buffered glycolate solution of pH=4, an americium(III) distribution ratio of 0.01 was obtained within 5 min of mixing. There was no evidence of degradation of the extractant, for example, the extraction performance of CyMe4-BTBP during hydrolylsis with 1 M nitric acid did not change over a two month contact.

Interaction of 6,6′′-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2′:6′,2′′-terpyridine (CyMe4-BTTP) with some trivalent ions such as lanthanide(iii) ions and americium(iii)

The new ligand 6,6 ''-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)2,2':6 ',2 ''-terpyridine (CyMe4-BTTP) has been synthesized in 4 steps from 2,2':6',2 ''-terpyridine. Detailed NMR and mass spectrometry studies indicate that the ligand forms 1 : 2 complexes with lanthanide(III) perchlorates where the aliphatic rings are conformationally constrained whereas 1 : 1 complexes are formed with lanthanide(III) nitrates where the rings are conformationally mobile. An optimized structure of the 1 : 2 solution complex with Yb(III) was obtained from the relative magnitude of the induced paramagnetic shifts. X-Ray crystallographic structures of the ligand and of its 1 : 1 complex with Y(III) were also obtained. The NMR and mass spectra of [Pd(CyMe4-BTTP)](n)(2n+) are consistent with a dinuclear double helical structure (n = 2). In the absence of a phase-modifier, CyMe4-BTTP in n-octanol showed a maximum distribution coefficient of Am(III) of 0.039 (+/-20%) and a maximum separation factor of Am(III) over Eu(III) of 12.0 from nitric acid. The metal(III) cations are extracted as the 1 : 1 complex from nitric acid. The generally low distribution coefficients observed compared with the BTBPs arise because the 1 : 1 complex of CyMe4-BTTP is considerably less hydrophobic than the 1 : 2 complexes formed by the BTBPs. In M(BTTP)(3+) complexes, there is a competition between the nitrate ions and the ligand for the complexation of the metal.

5,7-Dihydroxy-5,6,7,8-tetrahydro-1H-azocin-2-one from a marine-derived Streptomyces sp.

In the course of a screening program, we have isolated the new natural product, 5,7-dihydroxy-5,6,7,8-tetrahydroazocin-2(IH)-one (1), from the staurosporine producing marine-derived Streptomyces sp. strain QD518. Here we report the isolation and structure elucidation of 1 and the artifacts 3 and 4 resulting from I by acid catalyzed intra- and inter-molecular reactions.

Knoevenagel condensation of 2-carbethoxycyclohexanone and malononitrile: Synthesis of 4-cyano-3-ethoxy-1-hydroxy-5,6,7,8-tetrahydroisoquinoline, an isomer of the abnormal product

The structure of the abnormal product 1a formed in the Knoevenagel condensation of 2-carbethoxycyclohexanone and malononitrile has been further confirmed. Oxidation of the tetrahydroisoquinoline 3b using Na2Cr2O-AcOH-H2SO4 gave the keto isoquinoline 3d and the isoquinoline-1-carboxylic acid 5a. The acid chloride of 5a was condensed with diethyl ethoxymagnesiomalonate to afford after decarbethoxylation the methyl ketone 5d which on Baeyer-Villiger oxidation gave a mixture of the acetate 1g and the title compound 1b. The unambiguous synthesis of 1b confirms the structure assigned earlier to the title compound also formed during the partial hydrolysis of the diethoxy compound 1c. Condensation of 2-acetylcyclohexane-1,3-dione with malononitrile gave the quinoline derivative 4c which on ethylation yielded the ketoquinoline 4d. The present studies have confirmed that the quinoline compound 4a is also formed in the condensation of 2-acetylcyclohexanone and cyanoacetamide.

Ethyl 4-(3-hydroxyphenyl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

In the molecular structure of the title compound, C21H25NO4, the dihydropyridine ring adopts a flattened boat conformation while the cyclohexenone ring is in an envelope conformation. In the crystal structure, molecules are linked into a two-dimensional network parallel to (10 (1) over bar) by N-H center dot center dot center dot O and O-H center dot center dot center dot O hydrogen bonds. The network is generated by R-4(4)(30) and R-4(4)(34) graph-set motifs.

Amide-catalysed isomerisation of 5,6-dihydroisoquinolines: a novel synthesis of 1,2-dihydroisoquinolines

Knoevenagel condensation of 2-acylcyclohexanones or 2-ethoxycarbonylcyclohexanone with either cyanoacetamide or malononitrile followed by silver salt alkylation gave the 5,6,7,8-tetrahydroisoquinolines (3a–i). Chromic acid oxidation of the 5,6,7,8-tetrahydroisoquinolines (3a–i) to the corresponding tetralones (4a–i) followed by sodium borohydride reduction and p-toluenesulphonic acid-catalysed dehydration of the resulting alcohols (5a–i) gave the 5,6-dihydroisoquinolines (6a–i). Reaction of 5,6-dihydroisoquinolines (6a–g) with potassium amide in liquid ammonia gave a mixture of the 1,3-dihydroisoquinolines (7a–g) and the isoquinolines (8a–g). The C-1 unsubstituted 1,2-dihydroisoquinoline (7c) was found to be very unstable. In the case of the 5,6-dihydroisoquinolines (6h and 6i), reaction of potassium amide in liquid ammonia resulted in a mixture of 1-aminoisoquinoline (9) and the isoquinolines (8h and 8i). All the above compounds have been characterised by spectral data. A probable pathway for the formation of the 1,2-dihydroisoquinolines (7a–g) and the isoquinolines (8a–i) is suggested.

Amide-catalysed isomerisation of 5,6-dihydroisoquinolines: a novel synthesis of 1,2-dihydroisoquinolines

Knoevenagel condensation of 2-acylcyclohexanones or 2-ethoxycarbonylcyclohexanone with either cyanoacetamide or malononitrile followed by silver salt alkylation gave the 5,6,7,8-tetrahydroisoquinolines (3a–i). Chromic acid oxidation of the 5,6,7,8-tetrahydroisoquinolines (3a–i) to the corresponding tetralones (4a–i) followed by sodium borohydride reduction and p-toluenesulphonic acid-catalysed dehydration of the resulting alcohols (5a–i) gave the 5,6-dihydroisoquinolines (6a–i). Reaction of 5,6-dihydroisoquinolines (6a–g) with potassium amide in liquid ammonia gave a mixture of the 1,3-dihydroisoquinolines (7a–g) and the isoquinolines (8a–g). The C-1 unsubstituted 1,2-dihydroisoquinoline (7c) was found to be very unstable. In the case of the 5,6-dihydroisoquinolines (6h and 6i), reaction of potassium amide in liquid ammonia resulted in a mixture of 1-aminoisoquinoline (9) and the isoquinolines (8h and 8i). All the above compounds have been characterised by spectral data. A probable pathway for the formation of the 1,2-dihydroisoquinolines (7a–g) and the isoquinolines (8a–i) is suggested.

Hyperoxia Depletes (6R)-5,6,7,8-Tetrahydrobiopterin Levels in the Neonatal Retina: Implications for Nitric Oxide Synthase Function in Retinopathy

Retinopathy of prematurity is a sight-threatening complication of premature birth caused by nitrooxidativeinsult to the developing retinal vasculature during therapeutic hyperoxia exposure and laterischemia-induced neovascularization on supplemental oxygen withdrawal. In the vasodegenerativephase, during hyperoxia, defective endothelial nitric oxide synthase (NOS) produces reactive oxygenand nitrogen free radicals rather than vasoprotective nitric oxide for unclear reasons. More important,NOS critically depends on the availability of the cofactor (6R)-5,6,7,8-tetrahydrobiopterin (BH4).Because BH4 synthesis is controlled enzymatically by GTP cyclohydrolase (GTPCH), we used GTPCHdepletedmice [hyperphenylalanaemia strain Q4 (hph1)] to investigate the impact of hyperoxia on BH4bioavailability and retinal vascular pathology in the neonate. Hyperoxia decreased BH4 in retinas,lungs, and aortas in all experimental groups, resulting in a dose-dependent decrease in NOS activityand, in the wild-type group, elevated NOS-derived superoxide. Retinal dopamine levels were similarlydiminished, consistent with the dependence of tyrosine hydroxylase on BH4. Despite greater depletionof BH4, the hphþ/ and hph1/ groups did not show exacerbated hyperoxia-induced vessel closure,but exhibited greater vascular protection and reduced progression to neovascular disease. This vasoprotectiveeffect was independent of enhanced circulating vascular endothelial growth factor (VEGF),which was reduced by hyperoxia, but Q5 to local ganglion cell layerederived VEGF. A constitutively higherlevel of VEGF expression associated with retinal development protects GTPCH-deficient neonates fromoxygen-induced vascular damage.