Synthesis Of 1b Research Articles

A C 54 B 2 Polycyclic π-System with Bilayer Assembly and Multi-Redox Activity

A C ₅₄ B ₂ Polycyclic π-System with Bilayer Assembly and Multi-Redox Activity

Application of Relay C−H Oxidation Logic to Polyhydroxylated Oleanane Triterpenoids

Summary Although clinical applications of abundant feedstock triterpenoids such as oleanolic acid are limited because of poor solubility and bioavailability, synthetic access to higher hydroxylated oleanane terpenoids is challenging. We now report the use of relay C−H oxidation logic to mimic the processes carried out in nature by P450 monooxygenase enzymes. To this end, we used the C-23-OH as natural handle for a hydrogen-atom transfer to access C-6, enabling the first syntheses of highly oxidized natural products uncargenin C and protobassic acid as well as uncovering the anti-leukemic activity of a synthetic intermediate.

Synthesis of 3β-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene and Reductive Nucleophilic Attack on a Branched Aliphatic Aldehyde.

3β-tert-Butyldimethylsiloxy-22-phenylthio-23,24-bisnorchola-5,9(11)-diene, which has a double bond between C-9 and C-11 and a phenylsulfenyl group on the terminus of the side chain, is a potential synthetic intermediate for steroids with 9,11-unsaturation or 9,11-seco skeletons. We describe here the synthesis of the title compound from 17-ethylenedioxy-3-acetoxyandrosta-3,5-dien-11-one. The introduction of an ethylene unit to 3β-tert-butyldimethylsiloxyandrosta-5,9(11)-dien-17-one by the action of ethyltriphenylphosphonium bromide under basic conditions resulted in an inseparable mixture of two stereoisomeric products (5 : 1). However, in the subsequent step, only the (Z)-isomer was susceptible to the Lewis acid-catalyzed ene reaction with formaldehyde, giving a stereochemically pure product with the desired configuration. Within three steps, the ene-product was derivatized to the title compound, with a total yield of 53% over seven steps. Reductive terminal anion formation by treatment with lithium di-tert-butylbiphenyl (LiDBB) and subsequent nucleophilic attack on a branched aliphatic aldehyde was demonstrated, with an eye toward the introduction of side chains, especially for steroids with oxygen functionality at C-23.

Synthetic Studies for the 1,3‐Iterative Organoiron Approach to the Synthesis of Siculinine: Efficient Arylation Using a Diarylcuprate Reagent

AbstractDisubstituted (cyclohexadienyl)iron(1+) complex 2b is prepared by an improved route that starts from 1,2‐dimethoxycyclohexa‐1,4‐diene 3. In five steps, the synthesis of 2b is achieved by complexation with Fe(CO)5, hydride abstraction, hydrolysis, addition of EtO2CCH2ZrBr, and reaction with HBF4. In the presence of dimethyl sulfide, the reaction of 2b with 2‐[CH2N(CH2CH=CH2)2]‐functionalized diarylcuprate reagent 7 gave the 5α‐arylcyclohexadiene complex 1b in 88 % yield. A DFT study compared diarylzinc and diarylcuprate reagents containing chelating CH2NMe2 substituents.

Synthesis, characterization, reactivity and computational studies of new rhenium(I) complexes with thiosemicarbazone ligands derived from 4-(methylthio)benzaldehyde

N-thioamide thiosemicarbazone derived from 4-(methylthio)benzaldehyde (R = H, HL 1; R = Me, HL 2 and R = Ph, HL 3 ) have been prepared and their reaction with fac-[ReX(CO) 3(CH 3CN) 2] (X = Br, Cl) in methanol gave the adducts [ReX(CO) 3(HL n)] ( 1a X = Cl, n = 1; 1a′ X = Br, n = 1; 1b X = Cl, n = 2; 1b′ X = Br, n = 2; 1c X = Cl, n = 3; 1c′ X = Br, n = 3) in good yield. All the compounds have been characterized by elemental analysis, mass spectrometry (ESI), IR and 1H NMR spectroscopic methods. Moreover, the structures of HL 2 , HL 3 , HL 3 ·( CH 3) 2SO and 1b′·H 2O were also elucidated by X-ray diffraction. In 1b′, the rhenium atom is coordinated by the sulphur and the azomethine nitrogen atoms (κ S,N 3 ) forming a five-membered chelate ring, as well as three carbonyl and bromide ligands. The resulting coordination polyhedron can be described as a distorted octahedron. The structure of the dimers is based on rhenium(I) thiosemicarbazonates [Re 2(L 1) 2(CO) 6] ( 2a), [Re 2(L 2) 2(CO) 6] ( 2b) and [Re 2(L 3) 2(CO) 6] ( 2c) as determined by X-ray studies. Methods of synthesis were optimized to obtain amounts of these thiosemicarbazonate complexes. In these compounds the dimer structures are achieved by Re–S–Re bridges, where S is the thiolate sulphur from a κ S,N 3 -bidentate thiosemicarbazonate ligand. Some single crystals isolated in the synthesis of 2b contain [Re(L 4)(L 2)(CO) 3] ( 3b) where L 4 (=2-methylamine-5-(para-methylsulfanephenyl)-1,3,4-thiadiazole) is originated in a cyclization process of the thiosemicarbazone. Furthermore, the rhenium atom is coordinate by the sulphur and the thioamidic nitrogen of the thiosemicarbazonate (κ S,N 2 ) affording a four-membered chelate ring.

Cationic organozinc complexes of a bis(phosphinimine) pincer ligand: synthesis, structural and polymerization studies

Cationic organozinc complexes of a neutral bis(phosphinimine) pincer ligand (L) have been prepared and structurally characterized. This recently introduced ligand was constructed from a dibenzofuran (dbf) framework with symmetric attachment of phosphinimine groups at the 4 and 6 positions. Starting from protonated derivatives [LH][B(C(6)F(5))(4)] (1a), [LH][BPh(4)] (1b), or [LH(2)][BPh(4)](2) (1c), the complexes [LZnCH(3)][B(C(6)F(5))(4)] (2a), [LZnCH(3)][BPh(4)] (2b), and [LZnOAc][BPh(4)] (3), were prepared via protonolysis of an appropriate alkylzinc precursor. The complex [LZnPh][BPh(4)] (4) is generated as a side-product in the synthesis of 2b. Solid-state structural studies have revealed the compounds to be charge separated cationic zinc species with 3-coordinate trigonal planar geometry. Preliminary studies have shown these complexes to be inactive for the polymerization of lactide. Upon modification of the initiating group to a methyl-(S)-lactate, however, complex [LZnOCH(Me)CO(2)Me][B(C(6)F(5))(4)] (5) demonstrated significant polymerization activity at 60 degrees C. Additionally, NMR and mass spectrometry data confirmed a coordination-insertion mechanism was operative for this catalyst.

Synthesis of 3β, 7α, 11α-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives and their cytotoxic activities

A series of novel 3β, 7α, 11α-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives were synthesized and characterized by NMR, HRMS. The pregnenolone ( 1) was first biotransformed by Mucor circinelloides var lusitanicus to 3β, 7α, 11α-trihydroxy-pregn-5-en-20-one ( 3), then 3 was treated with various benzaldehydes to produce 3β, 7α, 11α-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives. These derivatives showed remarkable activity against EC109 cells. The absolute configuration of 3 was also confirmed by signal-crystal X-ray analysis.

Synthesis, Structure and Magnetic Behavior of Five-Coordinate Bis(iminopyrrolyl) Complexes of Cobalt(II) containing PMe3 and THF Ligands

The new bis-iminopyrrolyl five-coordinate Co(II) complexes [Co(kappa (2) N, N'-NC 4H 3C(R)N-2,6- (i)Pr 2C 6H 3) 2(PMe 3)] (R = H 3a; Me 3b) were synthesized in high yields (ca. 80-90%), using THF and diethyl ether as solvents, respectively, by (a) treatment of CoCl 2(PMe 3) 2 with the corresponding iminopyrrolyl Na salts ( Ie or If) or (b) reaction of anhydrous CoCl 2 and PMe 3 with Ie or If. A third route was tested, involving the addition of excesses of PMe 3 to the complexes [Co(kappa (2) N, N'-NC 4H 3C(R)N-2,6- (i)Pr 2C 6H 3) 2] (R = H 1e; Me 1f), which was only successful for the synthesis of 3a, in lower yields (ca. 30%). The synthesis of 3b in THF was unfruitful because of the kinetic competition of the solvent, giving rise to mixtures of 1f and its coordinated THF adduct 4b. The synthesis of the new bis-iminopyrrolyl five-coordinate Co(II) complexes [Co(kappa (2) N, N'-NC 4H 3C(R)N-2,6- (i)Pr 2C 6H 3) 2(THF)] (R = H 4a; Me 4b) were carried out in high yields (ca. 80-90%) by the reaction of CoCl 2(THF) 1.5 with the corresponding iminopyrrolyl Na salt. All the compounds have been characterized by X-ray diffraction, with 3a and 3b showing axially compressed trigonal bipyramidal geometry (with the PMe 3 ligand lying on the equatorial plane), whereas complexes 4a and 4b exhibit distorted square pyramidal geometries with the THF molecule occupying the axial position. Complex 4a shows clearly a compressed geometry, but for complex 4b, two polymorphs were characterized, exhibiting molecules with different Co-O (THF) bond lengths, one of them being compatible with an elongated form. Magnetic measurements either in the solid or in the liquid phases indicate that complexes 3a and 3b have low-spin ground states ( S = 1/2). In toluene solution, the geometry is fully confirmed by EPR data, which further indicates a d x (2) - y (2) /d xy ground state. However, compounds 4a and 4b behave unusually because they show magnetic moments that are compatible with high-spin ground states ( S = 3/2) in the solid state, but conform to low-spin ground states ( S = 1/2) when both complexes are dissolved in toluene solutions. The low-spin ground states in toluene solution are confirmed by EPR spectroscopy, which further supports, for complexes 4a and 4b, an axially elongated square pyramidal geometry and a d z (2) ground state. Thus the change in the ground-state and, consequently, in the geometry of complexes 4a and 4b from solid state to toluene solution might be a consequence of the elongation of the Co-O(THF) bond length. DFT studies performed on complexes 3 and 4 corroborate their different structure and magnetic behaviors and verify, for the latter complexes, the structural differences observed in the solid state and in toluene solution.

Redox reactivity and comprehensive synthetic chemistry of the perchloroditungstate [W 2(μ-Cl) 3Cl 6] n− ( n = 3, 2, 1) anions in organic media

The catalytic reactivity of the perchloroditungstate anions [W 2(μ-Cl) 3Cl 6] n − ( n = 3, 2, 1) [ n = 3, 2 ( W 2 6 + , a ′ 2 e ′ 4 ); n = 2, 3 ( W 2 7 + , a ′ 2 e ′ 3 ); n = 1, 4 ( W 2 8 + , a ′ 2 e ′ 2 )] in organic media remains unexplored, despite the facile redox activity of the W 2 n + core ( n = 4, 6–8), due to, among other reasons, the lack of simple and efficient methods for their synthesis. The preparation of salts of 2 with the bulky organic cations [ n Bu 4N + (TBA +, a); Ph 4P + (TPP +, b)] can be achieved in high yield from the room temperature reduction of WCl 4 with Na/Hg in toluene (∼90%), or from the reaction of W(CO) 6 with Me 3SiCl in boiling chlorobenzene (74%). Their oxidized counterparts 3a, b can be isolated in high yield directly from the oxidative decarbonylation of W(CO) 6 with 1,2-dichloroethane in the presence of TBACl or TPPCl in boiling chlorobenzene, or indirectly from the facile one-electron oxidation of 2a, b induced by (a) HCl (g) in organic aprotic solvents (CH 2Cl 2, THF, MeCN) or in biphasic media (aqueous HCl 6–12 M/CH 2Cl 2); (b) Lewis acids (SnCl 2, AlCl 3) in CH 2Cl 2; (c) various metal halide oxidants (FeCl 3, CuCl 2, HgCl 2) in organic media (CH 2Cl 2, THF, MeCN); and (d) carbon tetrachloride in solution (CH 2Cl 2, CCl 4) or in the solid state ( 2a, b/CCl 4). The redox chemistry (chemical or electrochemical) of the complexes in organic media, as well as their UV–Vis, ESI–MS, CV and EPR spectra are also reported. Examination of 2b by cyclic voltammetry in CH 2Cl 2 gives two reversible waves at −0.741 and −0.021 V versus Fc + / Fc, which are related spectroelectrochemically to the following successive one-electron processes: W 2 6 + → W 2 7 + → W 2 8 + . Thus, the synthesis of 3b can be accomplished by bulk electrolysis of 2b at 0.750 V. Whereas 2a, b do not react anaerobically with PhCH 2OH at ambient temperature, complexes 3a, b are reduced to 2a, b producing a mixture of PhCHO and PhCH 2Cl. The facile 2/ 3 redox chemistry and the capability of 3 in oxidizing PhCH 2OH makes this redox couple functional and of potential utility in catalytic oxidations of organic substrates.

Synthesis of 3β [L-Lysinamide-carbamoyl] Cholesterol Derivatives by Solid-Phase Method and Characteristics of Complexes with Antisense Oligodeoxynucleotides

In this report, we describe the synthesis of mono- and di-valent cationic [L-Lysinamide-carbamoyl] cholesterol (K-Chol) derivatives by solid-phase peptide synthesis method and the characteristics of K-Chol/antisense oligodeoxynucleotide (ODN) complexes. K-Chol was able to interact with antisense ODNs electrostatically and constructed nanometer-sized complexes of 50-100 nm in diameter. The formation of K-Chol/antisense ODN complexes was demonstrated by non-denaturing polyacrylamide gel electrophoresis assay and atomic force microscopy. The cell-associated radioactivity was measured to monitor the cellular uptake of the complexes containing radioactive antisense ODNs using HL 60 cells.

Synthesis of 3β,3β,5‐Tribromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one by Bromination of Dehydroacetic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis, Crystal Structure Analysis, and Pharmacological Characterization of Disila-bexarotene, a Disila-Analogue of the RXR-Selective Retinoid Agonist Bexarotene

Twofold sila-substitution (C/Si exchange) in the saturated ring of the tetrahydronaphthalene skeleton of the RXR-selective retinoid agonist bexarotene (1a) leads to disila-bexarotene (1b). Compound 1b was synthesized in a multistep synthesis, starting from 1,2-bis(chlorodimethylsilyl)ethane. The identity of 1b was established by elemental analyses and multinuclear NMR studies, and the C/Si analogues 1a and 1b (and an intermediate in the synthesis of 1b) were structurally characterized by single-crystal X-ray diffraction. Furthermore, 1a and 1b were studied for their interaction with retinoid X receptors. Although the twofold sila-substitution of 1a resulted in significant differences in the molecular structures of 1a and 1b, disila-bexarotene (1b) was shown to be a highly potent RXR agonist.

Synthesis of phthalates of betulinic acid and betulin with cytotoxic activity

Synthesis of 3β- O-phthalic esters from betulinic acid and its esters and synthesis of phthalic esters from betulin and its monoacetates using classical acylation procedure with phthalic anhydride. The evaluation of cytotoxicity of the prepared compounds was using numbers of tumor cell lines in MTT test. It was discovered that hemiphthalic esters had better cytotoxicity than starting compounds as betulinic acid or quite inactive betulin.

Synthesis of 4b,5,10a,11‐Tetrahydroindeno[1,2‐b]quinolin‐10‐ones from Baylis—Hillman Adducts.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reaction cascades initiated by nucleophilic attack of heteropentalene mesomeric betaine and nitrogen-rich mesoionic tetrazolium-5-amides on electron-deficient unsaturated compounds. Synthesis of novel heterocyclic systems.

The reactions of heteropentalene mesomeric betaine 1 and nitrogen-rich mesoionic tetrazolium-5-amides 4, 11 and 16-18 with electron-deficient unsaturated compounds have been studied. Novel heterocyclic systems, tetrazolo[4,5-a][1,7]benzodiazonine inner salt 2 and 3-oxo-3,7-dihydro-2H-pyrazolo[3,4-b]pyridine 5, have been synthesized by the reactions of dimethyl acetylenedicarboxylate with 1 and tetrazolium-5-anilide 4, respectively, and fully characterized by X-ray crystallography. It has been found that the reactions of other tetrazolium-5-amides are also initiated by the nucleophilic addition of the electron-rich amide nitrogen to the electron-deficient unsaturated compounds.

Synthesis and characterization of three-coordinate and related beta-diketiminate derivatives of manganese, iron, and cobalt.

Treatment of M[N(SiMe(3))(2)](2) (M = Mn, Fe, Co) with various bulky beta-diketimines afforded a variety of new three-coordinate complexes which were characterized by UV-vis, (1)H NMR and IR spectroscopy, magnetic measurements, and X-ray crystallography. Reaction of the beta-diketimine H(Dipp)NC(Me)CHC(Me)N(Dipp) (Dipp(2)N(wedge)NH; Dipp = C(6)H(3)-2,6-Pr(i)(2)) with M[N(SiMe(3))(2)](2) (M = Mn or Co) gave Dipp(2)N(wedge)NMN(SiMe(3))(2) (M = Mn, 1; Co, 3) while the reaction of Fe[N(SiMe(3))(2)](2) with Ar(2)N(wedge)NH (Ar = Dipp, C(6)F(5), Mes, C(6)H(3)-2,6-Me(2), or C(6)H(3)-2,6-Cl(2)) afforded the series of iron complexes Ar(2)N(wedge)NFe[N(SiMe(3))(2)] (Ar = Dipp, 2a; C(6)F(5), 2b; Mes, 2c; C(6)H(3)-2,6-Me(2), 2d; C(6)H(3)-2,6-Cl(2), 2e). This represents a new synthetic route to beta-diketiminate complexes of these metals. The four-coordinate bis-beta-diketiminate complex Fe[N(wedge)N(C(6)F(5))(2)](2), 4, was also isolated as a byproduct from the synthesis of 2b. Direct reaction of the Dipp(2)N(wedge)NLi with CoCl(2) gave the "ate" salt Dipp(2)N(wedge)NCoCl(2)Li(THF)(2), 5, in which the lithium chloride has formed a complex with Dipp(2)N(wedge)NCoCl through chloride bridging. The Fe(III) species Dipp(2)N(wedge)NFeCl(2), 6, was obtained cleanly from the reaction of FeCl(3) with Dipp(2)N(wedge)NLi. Magnetic measurements showed that all the complexes have a high spin configuration. The different substituents in the series of iron complexes 2a-e allowed assignment of their paramagnetically shifted (1)H NMR spectra. The X-ray crystal structures 1-2d and 3 showed that they have a distorted three-coordinate planar configuration at the metals whereas complexes 4-6 have highly distorted four-coordinate geometries.

Synthesis of novel 1,2,5-benzothiadiazepine 1,1-dioxides

3-Methoxycarbonyl-2-N-methyl-1,2,5-benzothiadiazepine 1,1-dioxide 2b can be obtained in seven unambiguous steps starting from commercially available l-serine methyl ester. The crucial step in the synthesis of 2b is the intramolecular Michael addition of dehydroalanine derivative 17, which can be achieved using sodium tert-butoxide as a non-nucleophilic base. An initial attempt to construct the same scaffold via an alternative strategy, which was based on a nucleophilic aromatic substitution as the key ring-closing step, proofed to be unsuccessful.

Si 2Me 4-bridged zirconocene dichlorides: crystal and molecular structure of meso-Si 2Me 4(3-SiMe 3–C 9H 5) 2ZrCl 2

A series of complexes Si 2Me 4L 2ZrCl 2 (L=Ind ( 1b), 2-Me–Ind ( 2b), 3-SiMe 3–Ind ( 3b) and Ind–H 4 ( 4)) was prepared. The syntheses of 1b, 3b and 4 gave predominantly the meso-isomers, whereas a 1:1 meso: rac mixture was obtained for 2b. X-ray analysis of meso- 3b revealed large steric hindrance on the metal center (Cp°–Zr–Cp° is 134.6°). The 1:1 mixture of meso- 2b and rac- 2b (activated with MAO) produced a 2.2:1 mixture of elastic atactic and isotactic polypropylene with low activity.

Synthesis of 3β-(4-[ 18F]fluoromethylphenyl)- and 3β-(2-[ 18F] fluoromethylphenyl)tropane-2β-carboxylic acid methyl esters: new ligands for mapping brain dopamine transporter with positron emission tomography

The synthesis of two new dopamine transporter ligands, 3β-(4-fluoromethylphenyl)tropane-2β-carboxylic acid methyl ester and 3β-(2-fluoromethylphenyl)tropane-2β-carboxylic acid methyl ester, and their spectral characterization are described. The precursors for these ligands were prepared by TiCl 4 catalyzed chloromethylation of 3β-phenyltropane-2β-carboxylic acid methyl ester followed by separation of the isomeric product mixture of 2- and 4-chloromethylphenyltropane derivatives. Reaction of the chloromethyl analogs with no-carrier-added [ 18F]fluoride ion followed by high performance liquid chromatography purification provided the corresponding [ 18F]fluoromethyltropanes, in good radiochemical yields, useful for imaging the brain dopamine transporter system in vivo with positron emission tomography.

Determination of 3-chloro- N-chloro- N-(3,4-dimethyl-5-isoxazolyl)-4-amine-1,2-naphthoquinone in presence of its degradation products using second derivative spectrophotometry

A rapid, selective and accurate method for stability determination of 3-chloro- N-chloro- N-(3,4-dimethyl-5-isoxazolyl)-4-amine-1,2-naphthoquinone ( 1b) in the presence of its degradation products by using second derivative UV spectrophotometry was developed. The validity of this method was proved using synthetic mixtures of the intact drug with its decomposition products and by statistical analysis of the calibration data. Lack of interference between the signals was observed in an interaction study. The synthesis of 1b and its degradation product 3-chloro-2-hydroxy- N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinon-4-imine ( 2b) are also described.