A common approach to the total synthesis of l-arabino-, l-ribo-C18-phytosphingosines, ent-2-epi-jaspine B and 3-epi-jaspine B from d-mannose

A common strategy for the total syntheses of the protected l-arabino- and l-ribo-C₁₈-phytosphingosine (8 and 9, respectively), HCl salts of ent-2-epi-jaspine B (ent-6) and 3-epi-jaspine B (7) with efficient use of both flexible building blocks 26 and 27 was achieved. The key step of this approach was [3,3]-sigmatropic rearrangement of allylic trichloroacetimidate 21 and thiocyanate 22, which were derived from the known 2,3:5,6-di-O-isopropylidene-d-mannofuranose 18 as the source of chirality. The side chain functionality was installed utilizing a Wittig reaction.     

Synthesis of the FG ring fragment of pectenotoxins 1-9

The synthesis of the FG ring fragment common to pectenotoxins 1-9 is reported. The successful, convergent synthesis relied on high yielding routes to access two key intermediates; aldehyde 1 and phosphonium salt 2. A Z-selective Wittig reaction gave access to advanced linear precursor 3, which was converted to FG ring fragment 4 using two sequential cyclization reactions.     

Disparate orientation of [1]rotaxanes

A novel [1]rotaxane 2 has been synthesized employing a 4-methyl-benzenesulfonyl and an azobenzene modified β-cyclodextrin (β-CyD) at the 2 position, through self-inclusion complexation and Suzuki-coupling capping in aqueous solution. Disparate absorption, induced circular dichroism (ICD) properties from its isomer [1]rotaxane 1, prepared from the isomeric β-CyD modifier at the 6 position, and the photoisomerization of [1]rotaxane 2 were thoroughly investigated.     

Tonkinensines A and B, two novel alkaloids from Sophora tonkinensis

Tonkinensines A (1) and B (2), two novel cytisine-type alkaloids that feature the skeleton with a linkage to pterocarpan, were isolated from the roots of Sophora tonkinensis. Their structures and absolute configurations were elucidated by spectroscopic methods, especially X-ray crystal diffraction and CD spectral analysis. The proposed biosynthetic pathway was also discussed. Both 1 and 2 were tested in HeLa and MDA-MB-231 tumor cell lines, and compound 2 showed moderate cytotoxic activity.     

Synthesis,structure and properties of [ML(NO3)2]: M = Co,Ni, Cu; L = N-(2-pyridylethyl)pyridine-2-carbaldimine

Syntheses of complexes of the type [ML(NO₃)₂], where M = Co(II), Ni(II), and Cu(II), L = N-(2-pyridylethyl)pyridine-2-carbaldimine, a tridentate ligand, are described. They were characterized by elemental analysis, spectral, magnetic, thermal studies, and X-ray crystallography. In the cobalt (1), nickel (2), and copper (3) complexes, the bivalent metal ion is coordinated by the three nitrogen atoms of the tridentate L with two pyridine-N groups occupying trans positions. Amongst the two nitrates one coordinates in a bidentate fashion while the other adopts a monodentate fashion. The X-band EPR spectra of 1, 2, and 3 in the polycrystalline state and in acetonitrile solution at 77 K are reported. Room temperature vibrating sample magnetometer data of 1, 2, and 3 afforded μ_eff values respectively of 3.928, 3.897, and 1.952 BM. The thermal stability order is 1 > 2 > 3, showing a reverse Irving-Williams trend.     

Palladium complexes of 8-(di-tert-butylphosphinooxy) quinoline

The preparation of the new ligand 8-(di-tert-butylphosphinooxy)quinoline (1) and the palladium derivatives [PdCl₂(1)] (2), [Pd(η³-all)(1)]⁺ [all = C₃H₅ (3a), 1-PhC₃H₄ (3b) and 1,3-Ph₂C₃H₃ (3c)] and [Pd(η²-ol)(1)] [ol = dimethyl fumarate (4a) and fumaronitrile (4b)] is reported. The cationic species 3a-3c have been isolated as salts. The complex 3a(BF₄) is obtained either from the reaction of 1 with [Pd(μ-Cl)(η³-C₃H₅)]₂ or from the reaction of ClP(CMe₃)₂ with [Pd(η³-C₃H₅)(8-oxyquinoline)], followed in both cases by chloride abstraction with NaBF₄. In the complexes, the ligand 1 is P,N chelated to the central metal, as shown by the X-ray structural analysis of 3a(BF₄). At 25 °C in solution, 3a(BF₄) and 3b(BF₄) undergo a fast η³−η¹−η³ dynamic process which brings about a syn-anti exchange only for the allylic protons cis to phosphorus, while for 4a and 4b a slow rotation of the olefin around its bond axis to palladium takes place. The complexes 2 and 3a(BF₄) are efficient catalyst precursors in the coupling of the phenylboronic acid with aryl bromides and chlorides.     

Synthesis of d-gluco-, l-ido-, d-galacto-, and l-altro-configured glycaro-1,5-lactams from tartaric acid

The d-gluco-, l-ido-, d-galacto-, and l-altro-configured glycaro-1,5-lactams 1-4 were prepared from the known tartaric anhydride 5 via the aldehyde 6. These lactams are known (1) or potential (2-4) inhibitors of β-d-glucuronidases and α-l-iduronidases. Olefination of 6 to the (E)- and (Z)-alkenes 7 or 8, followed by reagent or substrate controlled dihydroxylation, lactonization, azidation, reduction, and deprotection led in 10 steps and in overall yields of 11-20% to the title lactams.     

Stereochemistry and reactivity of F- and H-vinyldiazocarbonyl compounds and their phosphazines: synthesis of pyrazoles and pyridazines

3-(Trifluoromethyl)-substituted (F) 2-vinyl-2-diazocarbonyl compounds, having cis-relationship of functional groups (AlkO₂C, CN₂), do not undergo 1,5-electrocyclization, but readily take part in the tandem Staudinger-diaza-Wittig reactions to produce trifluoromethyl-substituted pyridazines, whereas their non-fluorinated analogs (H), with trans-configuration, easily cyclize to pyrazoles, but remain intact under Staudinger-diaza-Wittig reaction conditions. The difference in the reactivity of H- and F-vinyldiazoketones, vinyldiazoacetates, and derived phosphazines is apparently caused by the different stereochemical arrangements of the AlkO₂C and CN₂ groups.     

Synthesis and characterization of alkali-metal aryloxo compounds and their catalytic activity for l-lactide polymerization

Three new alkali-metal compounds stabilized by aryloxo groups were synthesized and fully characterized. The reactions of carbon-bridged bis(phenol)s MBMPH₂ (MBMPH₂ = 2,2′-methylene-bis(6-tert-butyl-4-methylphenol)) with sodium and potassium metals in tetrahydrofuran (THF) gave the desired alkali-metal complexes [MBMPNa₂(THF)₃]₂ (1) and [(MBMPK₂)₂(THF)₅]₂ (2), respectively, in high isolated yields. A similar reaction of aminophenol [HNOH] ([HNOH] = N-p-methyl-phenyl(2-hydroxy-3,5-di-tert-butyl)benzylamine) with sodium gave the monosodium salt [HNONa(THF)]₂ (3). Compounds 1-3 were well characterized, including X-ray structure determination. Compound 1 has a dimeric structure, and each sodium atom is four-coordinated with four oxygen atoms to form a distorted tetrahedron. Compound 2 has a centrosymmetric tetrameric structure. The coordination environments around the four potassium atoms are different. K1 is four-coordinated, K2 is three-coordinated, K3 is five-coordinated, whereas the coordination sphere of K4 is completed by one aryloxo oxygen atom and two oxygen atoms from two THF molecules and six carbon atoms from one arene ring of the bis(phenolate) ligand. Compound 3 has a dimeric structure, and each of the sodium atoms is four-coordinated to form a distorted tetrahedron. It was found that compounds 1-3 can efficiently initiate the ring opening polymerization of l-lactide in the absence of alcohol, yielding polymers with high molecular weights for a wide range of monomer-to-initiator ratios.     

Study on fluorescent switching of naphthopyran with carbazole and pyrene dyad immobilized on SBA-15

A naphthopyran-bridge-carbazole dyad (CzNP), which exhibits both fluorescence and photochromism was synthesized. Then the CzNP was grafted into SBA-15-NH₂, with particular focus on how the SBA-15-NH₂ affects the photoswitching fluorescence change properties. A double fluorescence photochromic material, which was prepared by reacting 1-Pyrenecardboxaldehyde(PY-CHO):naphthopyran-carbazole(CzNP)=1:1 (molar ratio) with SBA-15-NH₂ was also synthesized. Naphthopyran in this two systems displayed excellent photochromic performance. The fluorescent emission was modulated between ‘on’ and ‘off’ via the photoisomerization of naphthopyran in high-degree, especially in PY-CzNP-SBA-15-NH₂ (>90%) due to the photoinduced energy transfer from pyrene excimers to the opened-form naphthopyran and the photoinduced electron transfer between carbazoles and the opened-form naphthopyran moiety. Both the fluorescence photoswitching CzNP-SBA-15-NH₂ and PY-CzNP-SBA-15-NH₂ in CH₃CN/H₂O (v/v, 1:1) solution displayed excellent fatigue resistance. The structural characteristics of CzNP-SBA-15-NH₂ and PY-CzNP-SBA-15-NH₂ were measured by FTIR spectra, X-ray diffraction (XRD), and Elemental analysis.     

Characterization of two linear chain compounds: Ferromagnet NiCl2(CH3OH)2(1,4-dioxane)0.5 (1) and paramagnet [NiCl2(H2O)2(1,4-dioxane)](1,4-dioxane) (2)

The solvent-mediated crystal-to-crystal transformation was observed from yellow crystal of NiCl₂(CH₃OH)₂(1,4-dioxane)_0.5 (1) to green crystal of [NiCl₂(H₂O)₂(1,4-dioxane)](1,4-dioxane) (2) under high humidity or adding of H₂O in CH₃OH/1,4-dioxane solution. The μ-Cl₂ bridge in 1 replaced by 1,4-dioxane bridge in 2. In 1, the chlorine-bridged linear chains of NiCl₂(CH₃OH)₂ and 1,4-dioxane molecules stack along the b- and c-axis alternatively with hydrogen bonds intrachain, interchain, between chain and solvent. These hydrogen bonds and dipolar interaction between ferromagnetic coupling chlorine-bridged chains result in long-range ferromagnetic ordering at 3.1 K and a strong frequency dependence of the ac-susceptibilities associated to domain structures with very large shape anisotropy was observed below 3.1 K. In 2, layers of 1,4-dioxane-bridged linear chains of NiCl₂(H₂O)₂(1,4-dioxane) are intercalated by layer of 1,4-dioxane molecules with hydrogen bonds between chain and solvent. Compound 2 is paramagnet to 2 K.     

An efficient and novel synthesis of chromonyl chalcones using recyclable Zn(l-proline)2 catalyst in water

A novel approach was adopted for the synthesis of a series of chromonyl chalcones (3a-o) from 3-formylchromones (1a-c) and different cyclic active methyl compounds (2a-e), employing Zn(l-proline)₂ as a recyclable Lewis acid catalyst in water. In each conversion, the catalyst was successfully recovered and reused several times without significant loss in yield and selectivity. All the newly synthesized compounds were characterized using elemental analysis and spectral data (IR, ¹H NMR, ¹³C NMR and mass spectrometry).     

Synthesis and properties of novel 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-triones: methodology for synthesizing cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates

Novel condensation reaction of tropone with N-substituted and N,N′-disubstitued barbituric acids in Ac₂O afforded 5-(cyclohepta-2′,4′,6′-trienylidene)pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (8a-f) in moderate to good yields. The ¹³C NMR spectral study of 8a-f revealed that the contribution of zwitterionic resonance structures is less important as compared with that of 8,8-dicyanoheptafulvene. The rotational barriers (ΔG^‡) around the exocyclic double bond of mono-substituted derivatives 8a-c were obtained to be 14.51-15.03 kcal mol⁻¹ by the variable temperature ¹H NMR measurements. The electrochemical properties of 8a-f were also studied by CV measurement. Upon treatment with DDQ, 8a-c underwent oxidative cyclization to give two products, 7 and 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborates (11a-c·BF₄⁻ and 12a-c·BF₄⁻) in various ratios, while that of disubstituted derivatives 8d-f afforded 7,9-disubstituted cyclohepta[b]pyrimido[5,4-d]furan-8(7H),10(9H)-dionylium tetrafluoroborate (11d-f·BF₄⁻) in good yields. Similarly, preparation of known 5-(1′-oxocycloheptatrien-2′-yl)-pyrimidine-2(1H),4(3H),6(5H)-trione derivatives (14a-d) and novel derivatives 14e,f was carried out. Treatment of 14a-c with aq. HBF₄/Ac₂O afforded two kinds of novel products 11a-c·BF₄⁻ and 12a,c·BF₄⁻ in various ratios, respectively, while that of 14d-f afforded 11d-f. The product ratios of 11a-c·BF₄⁻ and 12a-c·BF₄⁻ observed in two kinds of cyclization reactions were rationalized on the basis of MO calculations of model compounds 20a and 21a. The spectroscopic and electrochemical properties of 11a-f·BF₄⁻ and 12a-c·BF₄⁻ were studied, and structural characterization of 11c·BF₄⁻ based on the X-ray crystal analysis and MO calculation was also performed.     

Synthesis,spectral, and structural investigation of [ML(NO3)2]: M = Co,Ni, Cu; L = N-(2-pyridylethyl)pyridine-2-methylketimine

Synthesis and structural characterization of distorted pentagonal bipyramidal Co(II), pseudo-octahedral Ni(II) and Cu(II) complexes of the type [ML(NO₃)₂], {L = N-(2-pyridylethyl)pyridine-2-methylketimine} are reported. Characterization includes elemental analysis, spectral, magnetism, and X-ray crystallographic studies. In case of cobalt (1) both the nitrates coordinate in bidentate fashion resulting overall distorted pentagonal bipyramidal geometry. In nickel (2) and copper (3) complexes, bivalent metal ion is coordinated by the three nitrogen atoms of the tridentate L with two pyridine-N occupying trans positions and amongst the two nitrates one coordinates in a bidentate fashion while other adopts a monodentate fashion. All the complexes exhibit d–d transitions in the visible region. Complex 1 is high-spin in nature and the X-band EPR spectra of 1, and 3 at room temperature and 77 K are reported.     

Efficient synthesis of new N-alkyl-d-ribono-1,5-lactams from d-ribono-1,4-lactone

d-Ribono-1,4-lactone was treated with ethylamine in DMF to afford N-ethyl-d-ribonamide 9a in quantitative yield. Bromination of amide 9a by the system SOBr₂ in DMF or PPh₃/CBr₄ in pyridine led, after acetylation, to epoxide 7. However, treatment of amide 9a with acetyl bromide in dioxane followed by acetylation gave 2,3,4-tri-O-acetyl-5-bromo-5-deoxyl-N-ethyl-d-ribonamide 10a. Methanolysis of 10a, with sodium methoxide, afforded the N-ethyl-d-ribonolactam 11a in 51% overall yields. Using this method, N-butyl, N-hexyl, N-dodecyl, and N-benzyl-d-ribonolactams 11b-e were obtained in good yields (48-53%).     

Synthesis of l-cyclopentenyl nucleosides using ring-closing metathesis and palladium-mediated allylic alkylation methodologies

The enantiomeric synthesis of l-cyclopentenyl nucleosides is described. The key intermediate (+)-cyclopentenyl alcohol (8) was prepared from methyl-α-d-galactopyranoside 1 using a ring closing metathesis reaction. Transformation of the allylic alcohol 8 into the allylic acetate (9) or carbonate (10), allows their coupling with purine and pyrimidine bases under Pd(0)-catalyzed Tsuji-Trost allylic alkylation's to yield 12a-c. The Pd catalyzed reaction was found to require the use of AlEt₃.     

Asymmetric syntheses of 6-deoxyfagomin, d-deoxyrhamnojirimycin, and d-rhamnono-1,5-lactam

N-Allyl protected 3-O-benzyloxglutarimide 11 was synthesized as a useful variant of the chiral building block 10. This modification allowed a high-yielding deprotection of the allyl group from the lactam intermediate 14. Starting from this building block, the asymmetric syntheses of aza-sugars 6-deoxyfagomine (2), d-rhamnono-1,5-lactam (6), as well as d-deoxyrhamnojirimycin (5) have been achieved in high regio- and/or diastereo-controlled manner.     

Convenient synthesis of antisepsis agent TAK-242 by novel optical resolution through diastereomeric N-acylated sulfonamide derivative

A convenient synthesis method of antisepsis agent TAK-242 ((R)-1) through diastereomeric resolution was developed. By condensation of racemate rac-1 with chiral acid (S)-O-acetylmanderic acid (6a), the desired diastereomer 5a was isolated with 98% de in 39% yield by simple crystallization. Deacylation of 5a with aq NaOH followed by recrystallization provided (R)-1 with 99% ee in 20% yield from rac-1.     

Synthesis, properties, and oxidizing function of 6-substituted 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]pyrrole-8(7H),10(9H)-dionylium tetrafluoroborates

Uracil-annulated heteroazulenes, 6-substituted 7,9-dimethylcyclohepta[b]pyrimido[5,4-d]pyrrole-8(7H),10(9H)-dionylium tetrafluoroborates 7a,b·BF₄⁻, which are the isoelectronic compounds of 5-dezazaflavin, were synthesized. X-Ray crystal analysis and MO calculations were carried out to clarify the structural characteristics of 7a,b·BF₄⁻. The stability of cations 7a,b is expressed by the pK_R+ values which were determined spectrophotometrically to be 10.9 and 11.2, respectively. The electrochemical reduction of 7a,b exhibited high reduction potentials at −0.84 and −0.87 (V vs Ag/AgNO₃) upon cyclic voltammetry (CV). A good linear correlation between the pK_R+ values and reduction potentials (E1_red) of 7a,b·BF₄⁻ and reference compounds 4·BF₄⁻ and 5·BF₄⁻ was obtained. In a search of the reactivity, reactions of 7a,b·BF₄⁻ with some nucleophiles, hydride and diethylamine, were carried out to clarify that the introduction of nucleophiles to give regio-isomers is dependent on the nucleophile. The photo-induced oxidation reactions of 7a,b·BF₄⁻ toward some alcohols under aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield [based on compounds 7a,b·BF₄⁻], suggesting the oxidizing function of 7a,b·BF₄⁻ toward alcohols in the autorecycling process.     

Density functional theory calculations and experimental parameters for mutarotation of 6-deoxy-l-mannopyranosyl hydrazine

The geometry and energy profiles of the mutarotation pathway present in the equilibrium of 6-deoxy-β-l-mannopyranosyl 2,4-dinitrophenylhydrazine (1a), 6-deoxy-l-mannose 2,4-dinitrophenylhydrazone (1b), and 6-deoxy-α-l-mannopyranosyl 2,4-dinitrophenylhydrazine (1c) were modeled by DFT calculations at B3LYP/6-31G(d) level affording ΔG_DFT=0.000 kcal/mol, ΔG_DFT=0.174 kcal/mol, and ΔG_DFT=3.411 kcal/mol, respectively. Experimentally, the β-l-pyranose 1a occurs in 50% followed by the acyclic structure 1b in 44% as well as by the α-l-anomer 1c in 6%. The conformations of 1a-c and their corresponding 2,3,4-triacetyl derivatives 2a-c were studied by molecular modeling and NMR spectroscopy. IR frequencies, NMR chemical shifts, and X-ray diffraction analysis were employed to compare theoretical with experimental structural parameters.