Rapid syntheses of (±)-pterocarpans and isoflavones via the gold-catalyzed annulation of aldehydes and alkynes

(±)-Pterocarpan and analogues (4a-c) have been synthesized efficiently via the annulation of salicylaldehydes (1a, 1b and 1c) and o-methoxymethoxylphenylacetylene (2a), followed by a one-pot reduction and acidic cyclization of the ketones (3a-c). In addition, isoflavone derivatives (5a-c) have been synthesized rapidly, in two steps, via the annulation of salicylaldehyde (1a) and arylacetylenes (2b, 2c and 2d), followed by IBX/DMSO oxidation of the isoflavanones (3d, 3e and 3f).     

Synthesis, conformation and PKC isozyme surrogate binding of indolinelactam-Vs, new conformationally restricted analogues of (−)-indolactam-V

New conformationally restricted analogues of tumor promoter (−)-indolactam-V (1), indolinelactam-Vs (8, 11) and their hexyl derivatives at position 1 or 7 (9, 10, 12, 13), were synthesized from 1. (3R)-Indolinelactam-V (8) adopted a conformation similar to the twist form of 1 with a cis amide, while the conformation of (3S)-indolinelactam-V (11) was close to that of the sofa form of 1 with a trans amide. 7-Hexyl derivatives of 8 and 11 (10, 13) showed binding affinities for C1 domains of protein kinase C (PKC) isozymes compared to 1, but exhibited little selectivity among these PKC isozymes. However, introduction of the hexyl group at position 1 of 8 and 11 significantly enhanced their binding selectivity for novel PKC isozymes. The best selectivity for novel PKC isozymes was observed in (3S)-1-hexylindolinelactam-V (12) with a sofa-like conformation. These results suggest that a sofa-restricted analogue of 1 with a hydrophobic chain at an appropriate position would be a promising lead for designing agents with a high selectivity for novel PKC isozymes.     

Highly efficient, multigram and enantiopure synthesis of (S)-2-(2,4′-bithiazol-2-yl)pyrrolidine

(S)-2-(4-Bromo-2,4′-bithiazole)-1-(tert-butoxycarbonyl)pyrrolidine ((S)-1) was obtained as a single enantiomer and in high yield by means of a two-step modified Hantzsch thiazole synthesis reaction when bromoketone 3 and thioamide (S)-4 were used. Further conversion of (S)-1 into trimethyltin derivative (S)-2 broadens the scope for further cross-coupling reactions.     

An efficient microwave assisted synthesis of novel class of Rhodanine derivatives as potential HIV-1 and JSP-1 inhibitors

(Z)-5-(2-(1H-Indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one (7a-q) derivatives have been synthesized by the condensation reaction of 3-phenyl-2-thioxothiazolidin-4-ones (3a-h) with suitably substituted 2-(1H-indol-3-yl)-2-oxoacetaldehyde (6a-d) under microwave condition. The thioxothiazolidine-4-ones were prepared from the corresponding aromatic amines (1a-e) and di-(carboxymethyl)-trithiocarbonyl (2). The aldehydes (6a-h) were synthesized from the corresponding acid chlorides (5a-d) using HSnBu₃.     

[4+2] Cycloaddition of 1-phosphono-1,3-butadiene with azo- and nitroso-heterodienophiles

Under microwave activation, diethyl 1-phosphono-1,3-butadiene (1) reacted with t-butyl azodicarboxylate (2) and o-nitrosotoluene (5) to furnish quantitatively [4+2] cycloadducts, 3-phosphono-3,6-dihydro-1,2-pyridazine (3) and 6-phosphono-3,6-dihydro-1,2-oxazine (6), respectively. Selective oxidation and/or reduction of 6 led to functionalized δ-aminophosphonic derivatives in cyclic (7, 8) and aliphatic series (9, 10). Intermediate 10 may be cyclized into 2-phosphono-2,5-dihydro-1-pyrrole (12).     

Solid-state and solution photocycloadditions of 4-acyloxy-2-pyrones with maleimide

Solid-state photosensitized reactions of 4-acyloxy-2-pyrones (1b,c) with maleimide (2) afforded endo-endo double-[4+2] cycloadducts (3b,c) with high stereoselectivity. Sensitized photoreactions of 1a-d with 2 in solution gave exo-endo double-[4+2] cycloadducts (4a-d). 2-Pyrones 1a-d were photolyzed to give carboxylic acids (5a-d) via their valence isomerization in the solid state and in solution. Such kinds of photoreaction of the 4-acyloxy-2-pyrones were dramatically different from regio- and stereoselective [2+2] cycloadditions of 4-alkyloxy-2-pyrones. The photoreaction mechanisms of 1 with 2 and 1 itself were analyzed by powder X-ray diffraction analysis and MO calculations.     

New phlegmarane-type, cernuane-type, and quinolizidine alkaloids from two species of Lycopodium

Two new phlegmarane-type alkaloids, cermizines A (1) and B (2), three new quinolizidine alkaloids, cermizine C (3) and senepodines G (4) and H (5), and a new C₁₆N₂ type alkaloid consisting of a quinolizidine and a piperidine ring, cermizine D (6), as well as two new cernuane-type alkaloids, cernuine N-oxide (7) and lycocernuine N-oxide (8), have been isolated together with cernuine (9) and lycocernuine (10) from the club moss Lycopodium cernuum and L. chinense. The relative stereochemistry of 1-4 and 6, and the absolute stereochemistry of 5, 7, and 8 were elucidated by combination of NOESY correlations, modified Mosher's method, chemical transformations, and computational methods. Cermizine D (6) might be a biosynthetic intermediate of cernuane-type alkaloids such as 7-10.     

Anti-Pseudomonas aeruginosa xanthones from the resin and green fruits of Cratoxylum cochinchinense

Cochinchinones I-L (1-3 and 13) along with 11 known xanthones (4-12, 14, and 15) were isolated from the resin and green fruits of Cratoxylum cochinchinense. In addition, four new acetylated compounds (16-19) were derivatized from 7-geranyloxy-1,3-dihydroxyxanthone (14) and 3-geranyloxy-1,7-dihydroxyxanthone (15). All compounds were characterized on the basis of spectroscopic analyses. The structures of cochinchinone I (1), a monoacetate (18) and a dibrosylate (20), were also confirmed by X-ray diffraction analysis. The antibacterial and antifungal activities of selected compounds were evaluated as well.     

Vinyl-addition polymerization of norbornene catalyzed by (pyrazol-1-ylmethyl)pyridine divalent iron, cobalt and nickel complexes

Complexes of 2-((3,5-dimethyl)-1H-pyrazol-1-ylmethyl)pyridine (L1), 2-((3,5-ditert-butyl-1H-pyrazol-1-yl)methyl)pyridine (L2), 2-((3,5-diphenyl)-1H-pyrazol-1-yl)methyl)pyridine (L3), 2-((3,5-bis(trifluoromethyl)-1H-pyrazol-1-ylmethyl)pyridine (L4) and 2,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)methyl)pyridine (L5) with cobalt(II), iron(II) and nickel(II), Ni(L1)Cl₂ (1), Co(L1)Cl₂ (2), Fe(L1)Cl₂ (3), Ni(L2)Cl₂ (4), Ni(L3)Cl₂ (5), Co(L3)Cl₂ (6), Fe(L3)Cl₂ (7), Ni(L4)Cl₂ (8) and Ni(L5)Cl₂ (9), were used as catalyst precursors to produce vinyl-addition type norbornene polymers. Both the identity of the metal center and nature of ligand affected the polymerization behaviour of the resultant catalysts. Nickel catalysts were generally more active than the corresponding iron and cobalt analogues. The polynorbornene produced have high molecular weights (0.5-2.1 × 10⁶ g/mol) and narrow molecular weight distributions. Analyses of polymer microstructure using NMR and IR spectroscopy confirmed the polymers produced to be vinyl-addition polynorbornene.     

Metal-organic coordination architectures of azole heterocycle ligands bearing acetic acid groups: Synthesis, structure and magnetic properties

Four new coordination complexes with azole heterocycle ligands bearing acetic acid groups, [Co(L¹)₂]_n (1), [CuL¹N₃]_n (2), [Cu(L²)₂·0.5C₂H₅OH·H₂O]_n (3) and [Co(L²)₂]_n (4) (here, HL¹=1H-imidazole-1-yl-acetic acid, HL²=1H-benzimidazole-1-yl-acetic acid) have been synthesized and structurally characterized. Single-crystal structure analysis shows that 3 and 4 are 2D complexes with 4⁴-sql topologies, while another 2D complex 1 has a (4³)₂(4⁶)-kgd topology. And 2 is a 3D complex composed dinuclear μ_1,1-bridging azido Cu^II entities with distorted rutile topology. The magnetic properties of 1 and 2 have been studied.     

Reactions of azulenes with 1,2-diaryl-1,2-ethanediols in methanol in the presence of hydrochloric acid: comparative studies on products, crystal structures, and spectroscopic and electrochemical properties

Although reaction of guaiazulene (1a) with 1,2-diphenyl-1,2-ethanediol (2a) in methanol in the presence of hydrochloric acid at 60 °C for 3 h under aerobic conditions gives no product, reaction of 1a with 1,2-bis(4-methoxyphenyl)-1,2-ethanediol (2b) under the same reaction conditions as 2a gives a new ethylene derivative, 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (3), in 97% yield. Similarly, reaction of methyl azulene-1-carboxylate (1b) with 2b under the same reaction conditions as 1a gives no product; however, reactions of 1-chloroazulene (1c) and the parent azulene (1d) with 2b under the same reaction conditions as 1a give 2-[3-(1-chloroazulenyl)]-1,1-bis(4-methoxyphenyl)ethylene (4) (81% yield) and 2-azulenyl-1,1-bis(4-methoxyphenyl)ethylene (5) (15% yield), respectively. Along with the above reactions, reactions of 1a with 1,2-bis(4-hydroxyphenyl)-1,2-ethanediol (2c) and 1-[4-(dimethylamino)phenyl]-2-phenyl-1,2-ethanediol (2d) under the same reaction conditions as 2b give 2-(3-guaiazulenyl)-1,1-bis(4-hydroxyphenyl)ethylene (6) (73% yield) and (Z)-2-[4-(dimethylamino)phenyl]-1-(3-guaiazulenyl)-1-phenylethylene (7) (17% yield), respectively. Comparative studies of the above reaction products and their yields, crystal structures, spectroscopic and electrochemical properties are reported and, further, a plausible reaction pathway for the formation of the products 3-7 is described.     

The high-temperature alicyclic ring contraction of 1,1-dichloroperfluorotetralin and the alicyclic ring opening of 1,1-dichloroperfluorobenzocyclobutene

The pyrolysis of 1,1-dichloroperfluorotetralin (4) in a stream of argon gives a mixture contained perfluoro-1-methyleneindan (1), perfluoro-3-methylindene (6), 1,1-dichloroperfluoroindan (2) and perfluoroindene (7), while copyrolysis of tetralin 4 with CHClF₂ gives a mixture of compounds 1, 6 in the absence of compounds 2 and 7. 1-Chloro-2-(1-chloro-2,2-difluorovinyl)-3,4,5,6-tetrafluorobenzene (12) is formed in the pyrolysis of 1,1-dichloroperfluorobenzocyclobutene (5) in a stream of argon as well as in a stream of CHClF₂.     

A convenient enantioselective synthesis of 3-asymmetrically substituted oxindoles as progesterone receptor antagonists

A convenient enantioselective synthesis of 3-asymmetrically substituted oxindoles is reported. Compound (2) prepared by radical cyclisation of (1) was used for the synthesis of racemic and enantiomerically pure 3-asymmetrically substituted oxindoles. Desulfurisation of (2) using Raney Ni yielded the racemate (5). Addition of (S)-1-phenylethanol to compound (2) yielded the diastereoisomer (21) the structure of which was determined using X-ray crystallography. Using a sequence of steps (21) was converted to the enantiomer (8). The enantiomer (9) was similarly prepared from (2) using (R)-1-phenylethanol.     

Preparation of new pyrido[3,4-b]thienopyrroles and pyrido[4,3-e]thienopyridazines

Two new types of pyrido-fused tris-heterocycles (1a,b and 2a,b) have been prepared from 3-aminopyridine in five/six steps. A synthetic strategy for the preparation of the novel pyrido[3,4-b]thieno[2,3- and 3,2-d]pyrroles (1a,b) and pyrido[4,3-e]thieno[2,3- and 3,2-c]pyridazines (2a,b) has been studied. The Suzuki cross coupling of the appropriate 2- and 3-thienoboronic acids (3,4) and 4-bromo-3-pyridylpivaloylamide (9) afforded the biaryl coupling products (10,11) in high yields (85%). Diazotization of the hydrolysed (2-thienyl)-coupling product (12) and azide substitution gave the 3-azido-4-(2-thienyl)pyridine intermediate (72%, 14). 3-Azido-4-(3-thienyl)pyridine (15) was prepared by exchanging the previous order of reactions. The desired β-carboline thiophene analogues (1a,b) were obtained via the nitrene by thermal decomposition of the azido precursors (14,15). By optimising conditions for intramolecular diazocoupling, the corresponding pyridazine products (72-83%, 2a,b) were afforded.     

Total synthesis of (+)-epiepoformin, (+)-epiepoxydon and (+)-bromoxone employing a useful chiral building block, ethyl (1R,2S)-5,5-ethylenedioxy-2-hydroxycyclohexanecarboxylate

Enantioselective total synthesis of (+)-epiepoformin 1, (+)-epiepoxydon 2 and (+)-bromoxone 3 using a chiral building block, ethyl (1R,2S)-5,5-ethylenedioxy-2-hydroxycyclo- hexanecarboxylate 6, is described. Since the synthesis afforded intermediates 18, 2 and 25, it accomplished a formal synthesis of (−)-theobroxide 19, (−)-phyllostine 22, (+)-herveynone 27 and (−)-asperpentyn 28. The usefulness of 6 for the synthesis of natural epoxycyclohexene derivatives was demonstrated.     

Agelasines O-U, new diterpene alkaloids with a 9-N-methyladenine unit from a marine sponge Agelas sp.

New diterpene alkaloids, agelasines O-U (1-7), have been isolated from an Okinawan marine sponge Agelas sp. The gloss structures and relative stereochemistries of 1-7 were elucidated from the spectroscopic data. Agelasines O-R (1-4) were the third examples of diterpene alkaloid with a 9-N-methyladenine and a pyrrole units. Agelasine O (1) has a halimane skeleton, while agelasines P-R (2-4) have a clerodane skeleton. Agelasines S-U (5-7) were new diterpene alkaloids with a 9-N-methyladenine unit consisting of a halimane skeleton, a labdane skeleton, and a clerodane skeleton, respectively. Agelasines O-R (1-4) and T (6) showed antimicrobial activities against several bacteria and fungi.     

Synthesis, photophysical and photochemical properties of highly soluble phthalocyanines substituted with four 3,5-dimethylpyrazole-1-methoxy groups

The synthesis and characterization of new peripherally tetra-3,5-dimethylpyrazole-1-methoxy substituted metal-free (4), zinc (5), nickel (6), cobalt (7), copper (8) and lead (9) phthalocyanines are described for the first time in this study. The photophysical (fluorescence quantum yields and fluorescence lifetimes) and photochemical (photodegradation and singlet oxygen quantum yields) properties of metal-free (4), zinc (5) and lead (9) phthalocyanines are studied in dimethylsulfoxide (DMSO). Nickel (6), cobalt (7) and copper (8) phthalocyanines (6-8) did not evaluate for this purpose due to transition metal and paramagnetic behavior of central metals in the phthalocyanine cavity. The fluorescence quenching behavior of metal-free (4), zinc (5) and lead (9) phthalocyanines are also investigated. The fluorescence emissions of these phthalocyanines are effectively quenched by 1,4-benzoquinone in DMSO.     

Sodium dithionite initiated reactions of 1-bromo-1-chloro-2,2,2-trifluoroethane with enol ethers of cyclic ketones

Sodium dithionite initiated reactions of 1-bromo-1-chloro-2,2,2-trifluoroethane (1) with methyl and trimethylsilyl ethers of cyclopentanone and cyclohexanone enols (2a-d) in a MeCN/H₂O system were investigated. 2-(2,2,2-Trifluoroethylidene)cyclopentanone (4a) and 2-(2,2,2-trifluoroethylidene)-cyclohexanone (4b), respectively, were obtained as the main products and isolated in reasonable yields. The reaction with a 1:1 mixture of 5- and 3-methyl substituted 1-methoxycyclohexenes, 2e and 2f, revealed strong influence of steric hindrance on the reaction rate; a mixture of 2-(2,2,2-trifluoroethylidene)-5-methylcyclohexanone (6) and 2-(2,2,2-trifluoroethylidene)-3-methylcyclohexanone (7) in a 9:1 ratio was formed. Ketones 4a and 4b were reduced to the corresponding alcohols 8 and 9 and the reaction of 4b with hydrazine gave an indazole derivative 10.     

Ferrocenylpyrazole—A versatile building block for hydrogen-bonded organometallic supramolecular assemblies

The crystal architectures of 5-ferrocenylpyrazole (1) and its metal complexes were investigated. Compound 1 can form non-solvated and chloroform-solvated crystals. In both cases, 1 forms a zigzag one-dimensional architecture via NH?N hydrogen bonds. The hydrogen bond exhibits a twofold disorder, which was shown to be static by solid-state ¹³C NMR. In the solvated crystal, the chloroform is released at 415 K, associated with melting of the crystal. The reaction of 1 with metal salts provided metal-centered ferrocenyl clusters [Zn(NO₃)₂(1)₄] (4), [Co(NO₃)₂(1)₄] (5), [CoCl₂(1)₄] (6), [Zn(NCS)₂(1)₂] (7), cis-[Pt(NH₃)₂(1)₂](PF₆)₂ (8), and trans-[Pt(NH₃)₂(1)₄](PF₆)₂ (9). In all of these complexes, 1 acts as a monodentate ligand. In 4, 5, and 7, the multinuclear units are joined via hydrogen bonds to form supramolecular chains. Two polymorphs were found for the crystals of 4. Both are composed of the same hydrogen-bonded chains, but their arrangements are different. 5-Ferrocenyl-1-tritylpyrazole (2) and 4-ferrocenyl-1-methylpyrazole (3) were also crystallographically characterized.     

Catalyst- and steric-controlled alkenylation via chemoselective C-H activation and C-Br activation in Heck reaction of methyl 1-(2-bromoaryl)-3-(2-furyl/thienyl)-5-oxopyrrolidine-2-carboxylates and diethyl 1-(2-bromoaryl)-3-(2-furyl/thienyl)-5-oxopyrrolidine-2,2-dicarboxylate derivatives

Pd(II)-catalyzed alkenylation of methyl 1-(2-bromoaryl)-3-(2-furyl/thienyl)-5-oxopyrrolidine-2-carboxylate derivatives 1(a-d) resulted in the formation of 3(a-d) exclusively via C-H activation in the heteroaryl moiety. Similar observations were observed for the corresponding diester analogues 4(a-d) to form 5(a-d). Normal Heck reaction, however, was observed in the case of 1(a-f) to furnish 2(a-f) when the reaction was carried out with Pd(0) catalyst generated in situ. Pd(0)-catalyzed vinylation of 4(a-f) via C-Br oxidation, however, failed due to steric reason.