Polyfluorinated arylnitrosamines

N-Methyl-, N-n-butyl-, N-t-butylperfluoroarylamines undergo nitrosation with nitrous acid to give the corresponding N-nitroso derivatives. Perfluoroaryl groups were selected from the benzene, indane, biphenyl, naphthalene and pyridine series. According to ¹H and ¹⁹F NMR spectra, N-nitroso-N-methyl derivatives of polyfluoroarenes consist of E and Z isomers with the former prevailing. The more bulky n-butyl group promotes an increase in the formation of Z isomers. Only Z isomers have been obtained from N-t-butyl derivatives of perfluorinated 4-toluidine and 4-aminopyridine. The structure of the Z isomer of N-nitroso-N-methylperfluoro-4-toluidine is confirmed by X-ray data.     

Gold(I)-catalyzed [4+2] cycloaddition of N-(hex-5-enynyl) tert-butyloxycarbamates

A study concerning the gold(I)-catalyzed transformation of N-(hex-5-enynyl) tert-butyloxycarbamates is described. The mild conditions employed allow the moderately efficient but stereoselective synthesis of a range of bicyclic carbamates following a formal [4+2] cycloaddition process.     

Cytotoxic cembranoids from the Red Sea soft coral, Sarcophyton auritum

Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of two new diterpene cembranoids; 2-epi-sarcophine (2) and (1R,2E,4S,6E,8R,11R,12R)-2,6-cembradiene-4,8,11,12-tetrol (4), as well as two known diterpene cembranoids, reported for the first time from this species, namely sarcophine (1) and (+)-7α,8β-dihydroxydeepoxysarcophine (3). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated cembranoids were found to display high cytotoxicity against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line).     

An effective C-C double bond formation via Cu(I)-catalyzed dehydrogenation

A dehydrogenation method using Cu(I) and either N,N-di-tert-butylthiadiaziridine 1,1-dioxide or N,N-di-tert-butyldiaziridinone is reported. The dehydrogenation allows a facile introduction of C-C double bond(s) into various carbocycles and heterocycles such as oxazolines and thiazolines.     

N-tert-Butyl-N-chlorocyanamide: a new reagent for the efficient preparation of gem-chloronitroso compounds

A new reagent for the efficient preparation of gem-chloronitroso compounds has been developed. The reaction of ketoximes with N-tert-butyl-N-chlorocyanamide takes place instantaneously in carbon tetrachloride at room temperature with excellent yields under mild conditions.     

Platypodiol a novel clerodane diterpene from Baccharis platypoda

There is an urgent need for effective leishmanicidal drugs to replace or supplement those in current use. Our group has been bioprospecting many Brazilian plants looking for potential new ‘hits’ to combat leishmaniasis. We found that Baccharis platypoda was one of the Asteraceae species that displayed leishmanicidal activity. We now describe the isolation of the new clerodane diterpene (1), named platypodiol after its ethanolic leaf extract. Its structure was determined by detailed NMR and ESI-TOF/MS/MS experiments. Considering the few publications about this species, this result has increased the phytochemical knowledge about B. platypoda.     

Facile preparation of cyclopropanes from 2-iodoethyl-substituted olefins and 1,3-dihalopropanes with zinc powder

Two efficient, simple, cheap, and environmentally benign preparations of cyclopropanes were achieved. One is the formation via 3-exo-trig manner from various electron-deficient 2-iodoethyl-substituted olefins with zinc powder in a mixture of t-butyl alcohol and water, and the other is the formation via 3-exo-tet manner from various 1,3-dihalopropanes with zinc powder in ethanol.     

Overlapping chemical and genetic diversity in Ligularia lamarum and Ligularia subspicata. Isolation of ten new eremophilanes and a new seco-bakkane compound

Root chemicals and DNA sequences were analyzed for Ligularialamarum samples collected in Yunnan and Sichuan Provinces of China and the relationship between the plant and Ligulariasubspicata, its taxonomically closest species, was examined. Both species produce furanoeremophilanes and eremophilan-8-one derivatives as the major components. Eleven new compounds, including a new seco-bakkane compound, were isolated. The two species were found to harbor overlapping intra-specific diversities with respect to the chemicals and the DNA sequences.     

Highly selective acetoxylation of sulfonamides via using phenyliodine(III) diacetate

A highly efficient acetoxylation reaction of N-aryl-arylsulfonamides has been developed, presumably proceeding via the selective functionalization of N-aryl C–H bonds. A stoichiometric amount of PhI(OAc)₂ was generally employed as the oxidation reagent, and various para-acetoxylated sulfonamide derivatives had been generated in excellent yields. This chemistry endowed an economic synthesis of valuable acetoxylated sulfonamides through direct C–O bond formation processes.     

Infectopyrone, a potential mycotoxin from Alternaria infectoria

A new metabolite, infectopyrone (1), has been isolated from the filamentous fungus Alternaria infectoria. The structure of 1 was elucidated by analysis of 2D NMR spectroscopic data. Compound 1 is an α-pyrone resembling known toxins, and is a useful phenotaxonomic marker for the A. infectoria species-group. Infectopyrone (1) was also produced by species within Stemphyllium and Ulocladium, and found in mouldy food.     

Diastereoselective synthesis of homo-N,O-nucleosides

A new class of homo-N,O-nucleosides has been designed, based on the 1,3-dipolar cycloaddition of C-substituted nitrones with allyl nucleobases. The N-methyl-C-ethoxycarbonyl nitrone 1, and the C-α-silyloxymethyl-N-methyl nitrone 7 have been exploited: the stereochemical features of the obtained nucleosides are dependent on the nature of the dipole. The results obtained with DFT calculations fully agree with the experimental results and successfully reproduce the experimentally observed reversal of endo/exo selectivity for nitrones 1 and 7.     

Electrochemical fluorination of N,N-dimethylperfluoroacylamides

The electrochemical fluorination (ECF) of N,N-dimethylperfluoroacylamides gives the corresponding perfluoro-N,N-dimethylacylamides in low yield. With increase of the number of carbon atoms in the perfluoroacyl radical the yield of the required perfluoro-N,N-dimethylacylamides is slightly increased.     

Syntheses and structures of zinc and tin(II) compounds with hemilabile N-silyl-tert-butylamido and N-silyl-p-tolylamido ligands that contain pendent tert-butoxy groups

Syntheses and solid-state structures of zinc and tin(II) compounds, containing the N-silyl-amide ligands (O^tBu)(NR)SiMe₂, R = ^tBu (L^tBu), or R = p-tolyl (L^pTol), are reported. The N-silyl amines were synthesized by modified published procedures from commercially available Me₂SiCl₂, ^tBuOH, and ^tBuNH₂, or p-Me-C₆H₄NH₂, respectively. Treatment of SnCl₂ with LiL^pTol furnished Sn(L^pTol)₂, which was X-ray structurally characterized and shown to contain two covalent Sn-N bonds and two asymmetrical O → Sn donor bonds. The single-crystal X-ray structure of Sn(L^tBu)₂ revealed a much more symmetrically-coordinated, pseudo-trigonal-bipyramidal tin atom. Aminolysis of diethylzinc with HL^pTol produced [EtZn(L^pTol)]₂, which crystallized as a centrosymmetric dimer, containing four-coordinate zinc atoms connected by bridging amides. Zinc dichloride, by contrast, reacted with two equivalents of LiL^tBu to produce the homoleptic, pseudo-spirocyclic Zn(L^tBu)₂.     

Polyhydroxylated macrolide isolated from the endophytic fungus Pestalotiopsis mangiferae

A new polyhydroxylated macrolide, named mangiferaelactone (1) was isolated from a solid culture of the endophytic fungus Pestalotiopsis manguiferae, together with ten known compounds [(6S,1′S)-LL-P880α; (6S,1′S,2′R)-LL-P880β; (1′S,2′R)-LL-880γ; (1′R)-dehydropestalotin; (−)-5-carboxylmellein; (−)-5-methylmellein; (−)-5-hydroxylmethylmellein; arabenoic acid; 5,6-dihydro-4-methoxy-2H-pyran-2-one; and the (−)-2-hexylidene-3-methylsuccinic acid]. P. manguiferae was isolated from Hyptis dilatata, a small shrub common in the central region of Panama. The structure of compound 1 was elucidated by a combination of spectroscopic methods (IR, MS, optical rotation, 1D and 2D NMR spectroscopy). The absolute configuration of 1 was established as 4R,7R,8R,9S by application of vibrational circular dichroism (VCD). Compound 1 showed a minimum inhibitory concentration (MIC) of 1.6863 mg/mL against Listeria monocytogenes, and 0.5529 mg/mL against Bacillus cereus. No activity was observed for compound 1 against Plasmodium falciparum or Trypanosoma cruzi; likewise, no cytotoxic activity was observed against A2058 and H522-T1 cells.     

Three practical approaches for the synthesis of novel 4,7-dihetarylpyrazolo[1,5-a][1,3,5]triazines

Novel 4,7-dihetarylpyrazolo[1,5-a][1,3,5]triazines were synthesized from three different approaches. The first one, involved a one-step reaction between 5-amino-3-hetaryl-1H-pyrazoles and O,S-diethyl hetaroylimidothiocarbonates or S,S-diethyl hetaroylimidodithiocarbonates under solvent-free conditions employing microwave irradiation as the energy source. In the second approach, conventional heating under reflux in DMF as solvent was used instead of the microwave irradiation; and the third one was achieved from a two-step sequence through the treatment of 5-amino-3-hetaryl-1H-pyrazoles with hetaroyl isothiocyanates and the subsequent S-alkylation and cyclization process in DMF as solvent. Some intermediates were isolated and characterized to support the regiochemistry of the studied reactions. The structures of the new compounds were unambiguously established by spectroscopic and analytical techniques.     

Conformational analysis of bridgehead-substituted bicyclo[m.m.m]alkanes and bicyclo[8.8.n]alkanes

Conformational analyses of bicyclo[m.m.m]alkanes where m=1-10 and of bicyclo[8.8.n]alkanes where n=1-7 bearing methyl groups on the bridgeheads were carried out using a Monte Carlo search strategy. In the bicyclo[m.m.m]alkane series, greater variability was observed for the inter-bridgehead distance for larger values of m. This suggests that properly substituted bicyclo[8.8.8]hexacosanes or larger ring systems might serve as molecular springs.     

Emervaridione and varioxiranediol, two new metabolites from the endophytic fungus, Emericella variecolor

Two new compounds, emervaridione and varioxiranediol, together with the three known compounds, stellatic acid, ergosterol and dihydroterrein, were isolated from the endophytic fungus, Emericella variecolor. The structures of emervaridione and varioxiranediol were established from spectroscopic and X-ray crystallographic analysis.     

Fluorinated phosphorus compounds: Part 8. The reactions of bis(fluoroalkyl) phosphorochloridates with sulfur nucleophiles

The reactivity of bis(fluoroalkyl) phosphorochloridates to nucleophiles is summarised. Previous data and the results described here indicate that reactivities decrease in the order: amines>alcohols>thiols. The synthesis of CF₃CH₂OP(O)(SEt)₂ in 30% yield was accomplished by treating CF₃CH₂OP(O)Cl₂ with two molar equivalents of EtSH and Et₃N in ether. The chloridates (CF₃CH₂O)₂P(O)Cl and (C₂F₅CH₂O)₂P(O)Cl did not react with MeSH in ether at −78 °C or when heated with Pb(SMe)₂ in benzene. Ethanethiol and propanethiol reacted with fluorinated chloridates in the presence of triethylamine to give thiolates (R_FO)₂P(O)SR in 13-41% yield where R_F was CF₃CH₂, C₂F₅CH₂, C₃F₇CH₂ or (CF₃)₂CH and R was Et or n-Pr. Similarly, reaction of phosphorobromidates (R_FCH₂O)₂P(O)Br, made by brominating the corresponding bis(fluoroalkyl) H-phosphonates, with benzenethiol gave derivatives (R_FCH₂O)₂P(O)SPh in 43 and 46% yield where R_F was CF₃ and C₂F₅, respectively. Treatment of the chloridothiolate Cl(EtO)P(O)SMe, prepared in two steps from triethyl phosphite, with fluoroalcohols and triethylamine in ether gave species R_FO(EtO)P(O)SMe in 62-74% yield where R_F was CF₃CH₂, C₂F₅CH₂, C₃F₇CH₂ or (CF₃)₂CH. The reactions of bis(trifluoroethyl) phosphorochloridate with 2-mercaptoethanol, 3-mercaptopropanol and ethane-1,2-dithiol gave several unexpected products whose structures were tentatively assigned.     

Rhodium(I) complexes with κP coordinated ω-phosphinofunctionalized alkyl phenyl sulfide, sulfoxide and sulfone ligands and their reactions with sodium bis(trimethylsilyl)amide and Ag[BF4]

Reactions of ω-diphenylphosphinofunctionalized alkyl phenyl sulfides Ph₂P(CH₂)_nSPh (n = 1, 1a; 2, 2a; 3, 3a), sulfoxides Ph₂P(CH₂)_nS(O)Ph (n = 1, 1b; 2, 2b; 3, 3b) and sulfones Ph₂P(CH₂)_nS(O)₂Ph (n = 1, 1c; 2, 2c; 3, 3c) with dinuclear chlorido bridged rhodium(I) complexes [(RhL₂)₂(μ-Cl)₂] (L₂ = cycloocta-1.5-diene, cod, 4; bis(diphenylphosphino)ethane, dppe, 5) afforded mononuclear Rh(I) complexes of the type [RhCl{Ph₂P(CH₂)_nS(O)_xPh-κP}(cod)]¹ (n/x = 1/0, 6a; 1/1, 6b; 1/2, 6c; 2/0, 8a; 2/1, 8b; 2/2, 8c; 3/0, 10a; 3/1, 10b; 3/2, 10c) and [RhCl{Ph₂P(CH₂)_nS(O)_xPh-κP}(dppe)] (n/x = 1/0, 7a; 1/1, 7b; 1/2, 7c; 2/0, 9a; 2/1, 9b; 2/2, 9c; 3/0, 11a; 3/1, 11b; 3/2, 11c) having the P^S(O)_x ligands κP coordinated. Addition of Ag[BF₄] to complexes 6-11 in CH₂Cl₂ led with precipitation of AgCl to cationic rhodium complexes of the type [Rh{Ph₂P(CH₂)_nS(O)_xPh-κP,κS/O}L₂][BF₄] having bound the P^S(O)_x ligands bidentately in a κP,κS (13a-18a, 15b-18b) or a κP,κO (13b, 14b, 13c-18c) coordination mode. Unexpectedly, the addition of Ag[BF₄] to 6a in THF afforded the trinuclear cationic rhodium(I) complex [Rh₃(μ-Cl)(μ-Ph₂PCH₂SPh-κP:κS)₄][BF₄]₂·4THF (12·4THF) with a four-membered Rh₃Cl ring as basic framework. Addition of sodium bis(trimethylsilyl)amide to complexes 6-11 led to a selective deprotonation of the carbon atom neighbored to the S(O)_x group (α-C) yielding three different types of organorhodium complexes: a) Organorhodium intramolecular coordination compounds of the type [Rh{CH{S(O)_xPh}CH₂CH₂PPh₂-κC,κP}L₂] (22a-c, 23a-c), b) zwitterionic complexes [Rh{Ph₂PCHS(O)_xPh-κP,κS/O}L₂] having κP,κS (21a, 21b) and κP,κO (20b/c, 21c) coordinated anionic [Ph₂PCHS(O)_xPh] ligands, and c) the dinuclear rhodium(I) complex [{Rh{μ-CH(SPh)PPh₂-κC:κP}(cod)}₂] (19). All complexes were fully characterized spectroscopically and complexes 15b, 15c, 12·4THF and 19·THF additionally by X-ray diffraction analysis. DFT calculations of zwitterionic complexes gave insight into the coordination mode of the [Ph₂PCHS(O)Ph] ligand (κP,κS versus κP,κO).