Determination of the absolute configuration of nodulisporacid A by the concise synthesis of four stereoisomers via three-component reaction and one-pot construction of the framework

Four stereoisomers of nodulisporacid A (1) were synthesized by the concise approach which includes three-component reaction and subsequent one-pot construction of the whole framework. The ¹H NMR comparison of the derivatives (10-12) revealed the absolute configuration of natural 1 to be 4R,4′R,6′R.     

5,10:13,14-Disecosteroids: novel modified steroids containing 10- and 9-membered rings

In this paper a synthetic pathway to the modified 5,10:13,14-bisfragmentation cholestane derivatives 8-14 is described. The synthesis involves introduction of the 5α- and 14α-hydroxyl groups in the cholestane molecule and subsequent cleavage of the C(5)-C(10) bond in 5α,14α-dihydroxycholestan-3β-yl acetate (4) with the HgO/I₂ reagent and the C(13)-C(14) bond in the stereoisomeric 14α-hydroxy-5,10-secosteroids 5 and 6 with the Pb(OAc)₄/I₂ reagent. Complete and unambiguous ¹H and ¹³C NMR resonance assignments of the obtained secosteroids, as well as the solution conformations of their 10- and 9-membered rings were determined by extensive analysis of 1D and 2D NMR spectral data. The structures and the solid-state conformations of 5,10-secosteroids 5-7 were confirmed by X-ray analysis. All diseco-compounds have a novel 5,10:13,14-disecocholestane skeleton.     

Synthesis of 1-fluoroindan-1-carboxylic acid (FICA) and its properties as a chiral derivatizing agent

1-Fluoroindan-1-carboxylic acid (FICA) (1) was designed and synthesized as its methyl ester (FICA Me ester) (4) in order to develop an efficient chiral derivatizing agent (CDA) which excels α-methoxy-α-(trifluoromethyl)phenylacetic acid (MTPA) in capability. FICA Me ester (4) was prepared by fluorination of methyl 1-hydroxyindan-1-carboxylate (3) with (diethylamino)sulfur trifluoride (DAST) and derived to the esters of racemic secondary alcohols by ester exchange reaction. The resulting Δδ_F value was large in the case of 2-butyl ester of FICA (5a), whereas not detectable in the case of the corresponding MTPA ester (6a). The magnitude of the Δδ_H values was similar to that of MTPA esters. The diastereomers of (R)-(−)-8-phenylmenthyl ester of FICA (5i) was separated and their ¹H NMR analyses revealed that the concept of the modified Mosher's method was successfully applied to 5i.     

Microwave-assisted synthesis and characterization of a new soluble metal-free and metallophthalocyanines peripherally fused to four 18-membered tetrathiadiaza macrocycles

Preparation of some novel symmetrically tetrasubstituted metal-free phthalocyanine (6) and metallophthalocyanines (7-10) containing four 18-membered tetrathiadiaza macrocycles moieties on peripheral positions has been achieved by cyclotetramerization reaction of phthalonitrile derivative (5) in a multi-step reaction sequence. Metal-free phthalocyanine (6) was synthesized by microwave irradiation of 13,24-bis[(4-methylphenyl)sulfonyl]-6,7,14,15,23,24-hexahydro-13H,22H-tribenzo[b,h,n][1,4,10,13,7,16]tetrathiadiazacyclo-octadecine-18,19-dicarbonitrile (5) in 2-(dimethylamino)ethanol. The metallophthalocyanines (7-10) were prepared by the reaction of the phthalonitrile compound (5) with NiCl₂, Zn(CH₃COO)₂, CoCl₂, CuCl₂ salts, respectively, by microwave irradiation in 2-(dimethylamino)ethanol for at 175 °C, 350 W. The new compounds were characterized by IR, ¹H NMR, ¹³C NMR, UV-Vis, elemental analysis and MS spectra data.     

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).     

Stereochemistry of the reaction of cis,trans,cis-2,4,6,8-tetraisocyanato-2,4,6,8-tetramethylcyclotetrasiloxane with triphenylsilanol and 1,1,3,3-tetraphenyldisiloxane-1,3-diol

All-cis-2,4,6,8-tetramethyl-2,4,6,8-tetrakis(triphenylsiloxy)cyclotetrasiloxane (4) and syn-1,3,9,11-tetramethyl-5,5,7,7,13,13,15,15-octaphenyltricyclo[9.5.1.1^3,9]octasiloxane (5) were synthesized by the reaction of cis,trans,cis-[MeSi(NCO)O]₄ (1) with Ph₃SiOH (2) and [Ph₂Si(OH)]₂O (3), respectively, in the presence of pyridine for the sake of investigating the synthesis of ladder polysilsesquioxanes with perfect siloxane frameworks. Their stereostructures were confirmed by nuclear magnetic resonance spectra and X-ray crystallography, which revealed that 4 and 5 did not retain the stereostructure of the precursor 1. This result was caused by the racemization of 1 with pyridine, and a subsequent nucleophilic substitution reaction of 1 with 2 or 3, including inversion and retention of the configuration at the silicon atoms.     

Synthesis and structures of dialkyl zirconium complexes with an [OSSO]-type bis(phenolate) ligand bearing a trans-1,2-cyclooctanediylbis(thio) unit

Dimethyl and bis[(trimethylsilyl)methyl] zirconium complexes ([OSSO]ZrR₂) [4, R = Me; 5, R = CH₂SiMe₃] having [OSSO]-type bis(phenolato) ligand 1 based on the trans-1,2-cyclooctanediylbis(thio) core have been synthesized by the reactions of the corresponding dichloro zirconium complex 3 with 2 equiv. of MeMgBr and Me₃SiCH₂MgCl, respectively, in Et₂O/toluene at −78 °C. The molecular structures of these complexes 3-5 were characterized by NMR spectroscopy, elemental analyses, and X-ray crystallography. ¹H and ¹³C NMR data of complexes 3-5 exhibited that they took the C₂-symmetry in solution in the NMR time scale. In the crystal structures of 3-5, each zirconium center lies at the center of a distorted octahedral coordination sphere with cis sulfur atoms and trans oxygen atoms, which adopts a cis-α [(Λ^∗,S^∗,S^∗)] configuration.     

Preparation, thermal properties, morphology, and microstructure of phosphorus-containing epoxy/SiO2 and polyimide/SiO2 nanocomposites

A phosphorus-containing tri-ethoxysilane (dopo-icteos) reacting from the nucleophilic addition reaction of 9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (dopo) and 3-(trieoxysilyl) isocyanate (icteos) was synthesized. The structure of dopo-icteos was confirmed by ¹H, ¹³C, ³¹P NMR and IR spectra. A triethylamine catalyzed mechanism for the dopo-icteos synthesis was proposed and verified by NMR spectra. The phosphorus-containing epoxy/SiO₂ and polyimide/SiO₂ nanocomposites were prepared from the in-situ curing of diglycidyl ether of bisphenol A (DGEBA)/4,4-diaminodiphenylmethane(DDM)/dopo-icteos, and imidization of poly(amic acid) of pyromellitic dianhydride (PMDA)/4,4′-oxydianiline (ODA)/dopo-icteos, respectively. The microstructure and morphology were investigated by ²⁹Si NMR, scanning electron microscope (SEM), EDS (Si and P mapping) analysis and atomic force microscope (AFM). The thermal properties, flame retardancy and dielectric properties of the organic-inorganic hybrids were investigated by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), limiting oxygen index (LOI), thermal gravimetric analysis (TGA) and dielectric analyzer (DEA).     

Microwave-assisted synthesis and characterization of novel metal-free and metallophthalocyanines containing four 14-membered tetraaza macrocycles

The novel tetrasubstituted metal-free phthalocyanine (6) and metallophthalocyanines (7, 8) bearing four 14-membered tetraaza macrocycles moieties on peripheral positions have been synthesized by cyclotetramerization reaction of phthalonitrile derivative (5) in a multi-step reaction sequence. The new compounds were characterized by a combination of IR, ¹H NMR, ¹³C NMR, UV-vis, elemental analysis and MS spectral data.     

Total synthesis of (−)-amathaspiramide F

The stereoselective total synthesis of the marine alkaloid, (−)-amathaspiramide F (1), was achieved from the α-hydroxy-α-ethynylsilane 2. The key steps involved in the synthesis were (1) the enolate Claisen rearrangement of the α-acyloxy-α-alkenylsilane for the stereoselective construction of the consecutive C5 and C9 chiral centers of 1 (erythro configuration), (2) the construction of aza-spirohemiaminal 28, and (3) dibromination during the final stage of the total synthesis. The reaction of the (Z)-α-acyloxy-α-alkenylsilane 22 possessing the Boc-homoallylglycine ester as the acyloxy group underwent stereoselective enolate Claisen rearrangement to give the desired erythro product 23. On the other hand, the reaction of the α-acyloxy-α-alkenylsilane (Z)-5 having Boc-proline gave the unexpected threo product 6. Oxidative cleavage of the vinylsilane group of 23 followed by treatment with heptamethyldisilazane as the methylamine equivalent gave aza-spirohemiaminal 28. The problematic regioselective dibromination to 28 was achieved using n-Bu₄NBrCl₂.     

Synthesis and characterization of novel trans-3-benzyl/(diphenyl)methyl/naphthyl seleno substituted monocyclic β-lactams: X-ray structure of trans-1-(4′-methoxyphenyl)-3-(diphenyl)methylseleno-4-(4′-methoxyphenyl)azetidin-2-one

Several novel trans-3-benzyl/(diphenyl)methyl/naphthylseleno substituted monocyclic β-lactams (5-7) have been synthesized in high yields. The reaction scheme inolves [2 + 2] cycloaddition (Staudinger) reaction between suitably substituted imines 4(a-h) and ketenes (B) accessed from 2-benzyl/(diphenyl)methyl/naphthylselenoethanoic acids (1-3) using POCl₃ and triethylamine in refluxing toluene. Characterization of these newly synthesized seleno substituted β-lactams has been performed by various spectroscopic techniques viz. NMR (¹H, ¹³C and ⁷⁷Se), FTIR, mass spectrometry and elemental analysis. The molecular structure of trans-1-(4′-methoxyphenyl)-3-(diphenyl)methylseleno-4-(4′-methoxyphenyl)azetidin-2-one (6b) has also been established with the help of single crystal X-ray analysis.     

Nucleophilic substitution approach to 4′-substituted thymidines by employing 4′-benzenesulfonyl leaving group

Synthesis of 4′-substituted thymidines was investigated based on nucleophilic substitution using organosilicon and organoaluminum reagents. Two substrates having a benzenesulfonyl leaving group at the 4′-position were prepared for this purpose: 1-[4-benzenesulfonyl-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-α-l-threo-pentofuranosyl]thymine (8α) and the 4′-(benzenesulfonyl)thymidine derivative (8β). The reaction of 8α with organosilicon reagents (Me₃SiCH₂CHCH₂ and Me₃SiN₃) in combination with SnCl₄ gave preferentially the 4′-substituted β-d-isomer: the 4′-allyl (12β) and 4′-azido (15β) derivatives, respectively. The reaction of 8α with AlMe₃, however, gave the 4′-methyl-α-l-isomer (16α) as the major product, presumably through an ion pair mechanism. By employing the substrate 8β in this reaction, the 4′-methylthymidine derivative (16β) was obtained exclusively in high yield. The 4′-ethyl (20β) and 4′-cyano (24β) derivatives were also synthesized by reacting 8β with the respective organoaluminum reagent.     

Syntheses, spectroscopic and structural characterizations and metal ion binding properties of Schiff bases derived from 4′-aminobenzo-15-crown-5

A series of benzyloxybenzaldehyde derivatives (1-4) were synthesized by the reactions of 4-(bromomethyl)benzonitrile with 4-hydroxy-3-methoxybenzaldehyde (vanillin), 2-hydroxy-3-methoxybenzaldehyde (o-vanillin), 2-hydroxy-4-methoxybenzaldehyde and 2-hydroxy-5-methoxybenzaldehyde. Condensation reactions among the new benzyloxybenzaldehyde derivatives (1-4) with 4′-aminobenzo-15-crown-5 yielded the new Schiff base compounds (5-8). Sodium complexes (5a-8a) and potassium complexes (5b-8b) were prepared with NaClO₄ and KI, respectively. All of these synthesized compounds were characterized on the basis of FT-IR, ¹H and ¹³C NMR, mass spectrometry and elemental analyses data. The solid state structures of compounds 8 and 5a were determined by X-ray crystallography. The extraction abilities of compounds 5-8 were also evaluated in CH₂Cl₂ by using several main group and transition metal picrates, such as Na⁺, K⁺, Pb²⁺, Cr³⁺, Ni²⁺, Cu²⁺ and Zn²⁺.     

Synthesis and characterization of metal-free and metallophthalocyanines containing N2S2-type macrocyclic moieties linked ferrocenyl groups

The new metal-free (4) and metallophthalocyanines (5) carrying macrocyclic moieties linked ferrocenyl groups have been synthesized by direct cyclotetramerization of the pre-cursor, 12,13-dicyano-4,7-bis(ferrocenylmethyl)-2,3,4,5,6,7,8,9-octahydrocyclobenzo[k]-4,7-diaza-1,10-dithiacyclododecine (3) which has been prepared by the macrocyclization reaction of 1,2-bis(2-iodoethylmercapto)-4,5-dicyanobenzene (1) with N,N′-ethylenebis-(ferroceneylmethyl)amine (2), in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a strong organic base. Nickel (II) phthalocyanine (5) was synthesized by the reaction of metal-free phthalocyanine with anhydrous NiCl₂ in dry quinoline. The target compound and its intermediates have been characterized by a combination of elemental analysis and ¹H, ¹³C NMR, IR, UV-Vis and MS spectral data.     

Synthesis of bulky tris[(dimethyl(alkyl/aryl)silyl)methyl]stannanes as radical based reducing agents

The synthesis of novel bulky tris[dimethyl(ethyl/benzyl/p-tolyl/α-naphthyl)silylmethyl]stannanes (1-4) is described. Alkylation of SnCl₄ with Me₂(ethyl/p-tolyl)SiCH₂MgBr (10-11) gave mainly the triorganotin chlorides [(Me₂(ethyl/p-tolyl)SiCH₂)]₃SnCl 14 and 15, which were isolated by silica gel chromatography. Reduction of 14 and 15 with LiAlH₄ in THF gave the corresponding triorganotin hydrides 1 and 2, respectively. [Me₂(benzyl/α-naphthyl)SiCH₂]₃SnCl 16 and 17, generated by the alkylation of SnCl₄ with Me₂(benzyl/α-naphthyl)SiCH₂MgBr 12 and 13, were inseparable from the minor product [Me₂(benzyl/α-naphthyl)SiCH₂]₂SnCl₂18 and 19, respectively. Treatment of the mixtures of 16/18 and 17/19 with NaOH furnished the corresponding mixtures of stannoxanes, from which the hexakisdistannoxanes [Me₂(benzyl/α-naphthyl)SiCH₂]₆Sn₂O 20 and 22 were isolated from the minor dialkyltin oxide derivatives [Me₂(benzyl/α-naphthyl)SiCH₂]₂SnO in good yields. Reduction of 20 and 22 with BH₃ in THF gave [Me₂(benzyl/α-naphthyl)SiCH₂]₃SnH (3 and 4), respectively in good yields. ¹H, ¹³C, ¹¹⁹Sn, ²⁹Si NMR characteristics of the newly synthesized compounds are included.     

Synthesis, characterization, and cyclometalation studies of benzo[1,2-h: 5,4-h′]diquinolines with palladium and platinum

Benzo[1,2-h: 5,4-h′]diquinoline(1a) represents a new family of tridentate NCN pincer ligand. We report the synthesis of the parent ligand (1a) and its derivatives (1b R = Me, 1c R = t-Butyl, 1d R = Phenyl). The ligands were characterized by ¹H and ¹³C NMR, as well as mass spectral analysis, and X-ray structural determination. They readily undergo cyclometalation with LiPdCl₄, Pd(OAc)₂, and K₂PtCl₄ to form the cyclometalated Pd(NCN)Cl (2a-c, 3a), and Pt(NCN)Cl (4a) pincer complexes. These complexes have been characterized through NMR, and mass spectrometry. PdNCNCl (2a) structure was determined by single crystal X-ray diffraction. Complex 2a has shown to catalyze the Heck coupling reaction between bromobenzene and n-butylacyrlate in NMP at 140 °C, TON of 2506 were observed.     

Structural properties of new spiro-1,3-propanediaminocyclotriphosphazene derivatives

New 1,3-propanediaminocyclotriphosphazene derivatives (7-17) were synthesized from the reactions of spiro-1,3-propanediaminocyclotriphosphazene, N₃P₃Cl₄[NH(CH₂)₃NH] (1) with the cyclopropanemethylamine (2), cyclohexylamine (3), pyrrolidine (4) cyclohexanol (5), cyclopropylmethanol (6). The structures of the novel compounds (7-17) were characterized by elemental analysis, mass spectrometry, ¹H and ³¹P NMR spectroscopy. The molecular structures of 8, 12 and 13 were determined by X-ray crystallography. The structures of all these three compounds are in the monoclinic crystal system; compounds 8 and 12 have the P21/c space group while compound 13 has the P21/n space group. The ring conformation of the cyclotriphosphazene and other external rings were investigated based on the X-ray crystal structures.     

Aqueous syntheses of [(Cp-R)M(CO)3] type complexes (Cp = cyclopentadienyl, M = Mn, Tc, Re) with bioactive functionalities

We describe reactions of [^99mTc(H₂O)₃(CO)₃)]⁺ (1) with Diels-Alder products of cyclopentadiene such as “Thiele’s acid” (HCp-COOH)₂ (2) and derivatives thereof in which the corresponding [(Cp-COOH)^99mTc(CO)₃)] (3) complex did form in water. We propose a metal mediated Diels-Alder reaction mechanism. To show that this reaction was not limited to carboxylate groups, we synthesized conjugates of 2 (HCp-CONHR)₂ (4a-c) (4a, R = benzyl amine; 4b, R = N_α-Boc-l-2,3-diaminopropionic acid and 4c, R = glycine). The corresponding ^99mTc complexes [(4a)^99mTc(CO)₃)] 6a, [(4b)^99mTc(CO)₃)] 6b and [(4c)^99mTc(CO)₃)] 6c have been prepared along the same route as for Thiele’s acid in aqueous media demonstrating the general applicability of this synthetic strategy. The authenticity of the ^99mTc complexes on the no carrier added level have been confirmed by chromatographic comparison with the structurally characterized manganese or rhenium complexes.Studies of the reaction of 1 with Thiele’s acid bound to a solid phase resin demonstrated the formation of [(Cp-COOH)^99mTc(CO)₃)] 3 in a heterogeneous reaction. This is the first evidence for the formation of no carrier added ^99mTc radiopharmaceuticals containing cyclopentadienyl ligands via solid phase syntheses. Macroscopically, the manganese analogue 5a and the rhenium complexes 5b-c have been prepared and characterized by IR, NMR, ESI-MS and X-ray crystallography for 5a (monoclinic, P2₁/c, a = 9.8696(2) Å, b = 25.8533(4) Å, c = 11.8414(2) Å, β = 98.7322(17)°) in order to unambiguously assign the authenticity of the corresponding ^99mTc complexes.     

New stibines containing acetal and formyl group: Platinum complex and unexpected oxastibol derivative

A new tertiary stibine ligand (1) containing acetal group at the ortho-position has been synthesized. This new stibine was then complexed with to obtain trans-PtCl₂L₂ (2) where stibine acts as a monodentate ligand. The acetal was hydrolyzed in a slightly acidic medium and forms a very new stibine (3) containing formyl group at the ortho-position. When (3) was reduced with NaBH₄ an unusual oxastibol (4) derivative was obtained under the experimental conditions used.All the compounds were characterized by IR, mass, ¹H, ¹³C, COSY and HETCOR NMR spectroscopy. The molecular structures of (2), (3) and (4) were determined. Compound (3) crystallizes in two different polymorphs (3a) and (3b) and both the polymorphs show hypervalent antimony with three Sb?O interactions and the molecule exists in O-cis-exo configuration. Compound (4) shows intramolecular Sb?O interactions. To the best of our knowledge this is the first report on organoantimony compounds containing carbonyl groups though their phosphorus and bismuth analogues are well known. Compound (2) shows helicoidal chirality, which is a very new concept in antimony chemistry