A comparison of electron impact mass spectrometry of isomeric pyranocoumarins (pyrano[3,2-c][1]benzopyran-5-ones) and pyranochromones (pyrano[2,3-b][1]benzopyran-5-ones)

The mass spectrometric behaviour of two pairs of isomeric 2,2-dimethylpyrano[3,2-c][1]benzopyran-5-ones (pyranocoumarins) and 2,2-dimethylpyrano[2,3-b][1]benzopyran-5-ones (pyranochromones) and four pairs of isomeric 2-hydroxymethyl-2-methylpyrano[3,2-c][1]benzopyran-5-ones (pyranocoumarins) and 2-hydroxymethyl-2-methylpyrano[2,3-b][1] benzopyran-5-ones (pyranochromones) has been studied in detail with the aid of exact mass measurements, linked scans, collisionally activated decompositions and deuterium labelling experiments. The presence in both series of compounds of the same ions derived by structural interconversion of both molecular ions is emphasized, and structural information on the ions [C₇H₅O₂]⁺ (m/z 121), highly characteristic for these classes of compounds, as for 4-hydroxycoumarins, is reported.     

Synthesis of purine nucleosides built on a 3-oxabicyclo[3.2.0]heptane scaffold

The photochemical [2 + 2] cycloaddition of chiral 3-chloro and 3-fluoro-5-hydroxymethyl-2(5H)-furanone to ethylene and acetylene has been studied. The effect of the halogen atom on the chemical yield and facial diastereoselectivity of the cycloaddition process has been evaluated. From the major anti cycloadducts, practical syntheses of several purine cyclobutane and cyclobutene-fused nucleosides containing a halogen atom have been developed. The anti-HIV activity of the new nucleoside analogues has been evaluated.     

A convenient method for 14C-labeling of 2-methylthio-1-[4-N-α-ethoxycarbonylbenzyl)-amino-benzyl]-5-hydroxymethyl-2-[14C]-1H-imidazole and 1-[4-N-α-ethoxy-carbonylbenzyl)-aminobenzyl]-5-hydroxymethyl-2-[14C]-1H-imidazole as potential antihypertensives

The key synthetic intermediate, (2-mercapto-1-(4-nitrobenzyl)-1H-imidazol-5-yl)methanol-[2-¹⁴C], has been synthesized by using one pot procedure from potassium[¹⁴C]-thiocyanate. It was converted to two nonpeptide angiotensin II receptor antagonists, 2-methylthio-1-[4-N-α-ethoxycarbonyl benzyl)-aminobenzyl]-5-hydroxymethyl-1H-imidazole-[2-¹⁴C] and 1-[4-N-α-ethoxy-carbonylbenzyl)-aminobenzyl]-5-hydroxymethyl-1H-imidazole-[2-¹⁴C] via a 3-step sequence synthetic pathway.     

5-Hydroxymethyl-2'-deoxyuridine. Cytotoxicity and DNA incorporation studied by using a novel [2-14C]-derivative with normal and leukemic human hematopoietic cells

5-Hydroxymethyl-2'-deoxyuridine is a biologically active thymidine analogue. This investigation was aimed at characterizing the cytotoxicity of 5-hydroxymethyl-2'-deoxyuridine and its incorporation into DNA. Fifty percent inhibition of cellular proliferation, assessed by incorporation of [U-14C]-L-leucine in vitro, was caused by 1.7-5.8 X 10(-5) incorporation of [U-14C]-L-leucine in vitro, was caused by 1.7-5.8 X 10(-5) M 5-hydroxymethyl-2'-deoxyuridine in seven human leukemia cell lines. Higher concentrations of 5-hydroxymethyl-2'-deoxyuridine, i.e. 6-8 X 10(-5) M, were required for a comparable inhibition in human PHA-stimulated peripheral blood lymphocytes. A new synthesis procedure for [2-14C]5-hydroxymethyl-2'-deoxyuridine was developed. The net incorporation of [2-14C]5-hydroxymethyl-2'-deoxyuridine into DNA of hematopoietic cells was low. The possibility of a repair mechanism for 5-hydroxymethyluracil bound to DNA is discussed.     

The rearrangement route to 3-CH(2)X-2-azabicyclo[2.1.1]hexanes. Substituent control of neighboring group participation

The stereocontrolled synthesis of a functionalized 3-hydroxymethyl-2-azabicyclo[2.1.1]hexane synthon for a variety of methano-bridged pyrrolidines has been effected. The key step in an electrophilic addition-rearrangement route uses a 3-nosyloxymethyl group in the 2-azabicyclo[2.2.0]hex-5-ene precursor in order to suppress unwanted competitive oxygen neighboring group participation. [reaction: see text]     

Studies on the constituents of Broussonetia species. VII. Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, as inhibitors of glycosidase, from Broussonetia kazinoki SIEB

Four new pyrrolidine alkaloids, broussonetines M, O, P, and Q, were isolated from the branches of Broussonetia kazinoki SIEB, (Moraceae). Broussonetines M, O, P, and Q were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(10S)-10,13-dihydroxy-tri decyl]pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)9-oxo-13-hydroxy-3- tridecenyl]pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)10-oxo-13-hydroxy-3-++ +tridecenyl]pyrrolidine (3), and (2R,3S,4R,5R)-2-hydroxymethyl-3-hydroxy-4-(beta-D-glucopyranosyloxy++ +)-5-[10-oxo-13-(beta-D-glucopyranosyloxy)tridecyl]pyrrolidine (4) respectively, by spectroscopic and chemical methods. 1-4 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.     

Electron impact mass spectrometry of 3-hydroxy-3,4,5,6-tetrahydro-2H-[1]benzoxocines. A comparison with the behaviour of isomeric 2-hydroxymethyl-2,3,4,5-tetrahydro-[1]-benzoxepines and 1,2-epoxy-5-(2-hydroxyphenyl)pentane

The mass spectrometric behavior of 3-methyl-3-hydroxybenzoxocines has been studied in detail by means of linked scans and mass analyzed ion kinetic energy spectrometry. The structure of the molecular ion and the fragmentation processes are strictly related to the structure of the neutral moieties. The possible isomerization of 3-hydroxy-10-methoxy-3-methyl-3,4,5,6-tetrahydro-2H-[1]benzoxocine to 2-methyl-2-[3-(3′-methoxy-2′-hydroxy)phenyl]pentyloxirane and to 2-hydroxymethyl-9-methoxy-2-methyl-2,3,4,5-tetrahydro[1]benzoxepine is investigated.     

Transition metal-catalyzed hetero-[5 + 2] cycloadditions of cyclopropyl imines and alkynes: dihydroazepines from simple,readily available starting materials

The first example of a transition metal-catalyzed hetero-[5 + 2] cycloaddition reaction is described. Use of cyclopropyl imines as five-atom components, an alkyne as a two-carbon component, and a Rh(I) catalyst enables a new route to dihydroazepines. This new hetero-[5 + 2] cycloaddition works well with aldimines, ketimines, and with substituted cyclopropanes and affords the desired dihydroazepines in excellent yields as single regioisomers. Use of serial imine formation/aza-[5 + 2] cycloaddition generates the desired dihydroazepines in one operation from three commercially available starting materials. The reaction has been scaled to give gram quantities of dihydroazepine.     

Total Synthesis of (+)‐Asteriscanolide: Further Exploration of the Rhodium(I)‐Catalyzed [(5+2)+1] Reaction of Ene‐Vinylcyclopropanes and CO

The total synthesis of (+)‐asteriscanolide is reported. The synthetic route features two key reactions: 1) the rhodium(I)‐catalyzed [(5+2)+1] cycloaddition of a chiral ene‐vinylcyclopropane (ene‐VCP) substrate to construct the [6.3.0] carbocyclic core with excellent asymmetric induction, and 2) an alkoxycarbonyl‐radical cyclization that builds the bridging butyrolactone ring with high efficiency. Other features of this synthetic route include the catalytic asymmetric alkynylation of an aldehyde to synthesize the chiral ene‐VCP substrate, a highly regioselective conversion of the [(5+2)+1] cycloadduct into its enol triflate, and the inversion of the inside–outside tricycle to the outside–outside structure by an ester‐reduction/elimination to enol‐ether/hydrogenation procedure. In addition, density functional theory (DFT) rationalization of the chiral induction of the [(5+2)+1] reaction and the diastereoselectivity of the radical annulation has been presented. Equally important is that we have also developed other routes to synthesize asteriscanolide using the rhodium(I)‐catalyzed [(5+2)+1] cycloaddition as the key step. Even though these routes failed to achieve the total synthesis, these experiments gave further useful information about the scope of the [(5+2)+1] reaction and paved the way for its future application in synthesis.     

A polarographic study of the iron-2-hydroxymethyl-6-(2′-hydroxymethyl-5′-hydroxy-4′-pyrone-6′)-pyranyl-3,2[b]pyran-4,8-dione complex

A polarographic study has been carried out on the colored product formed in the interaction of iron(III) with 2-hydroxymethyl-6-(2′-hydroxymethyl-5′-hydroxy-4′-pyrone-6′)-pyranyl-3,2[b]pyran-4,8-dione. Measurements using the differential pulse method show that iron(III) exhibits a coordination number of 2 and a reproducible formation constant that varies somewhat depending upon the supporting electrolyte employed.     

Studies on the constituents of Broussonetia species VIII. Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U, from Broussonetia kazinoki Sieb

Four new pyrrolidine alkaloids, broussonetines R, S, T, and V and a new pyrroline alkaloid, broussonetine U were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae) in low yield. Broussonetines R, S and T were formulated as (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R)-1-hydroxy-3-[6-(4-hydroxybutyl)-cyclohexy-2-on-1(6)-enyllpropyl] pyrrolidine (1), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,10S)-1,10,13-trihydroxytridecyl] pyrrolidine (2), (2R,3R,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(1R,5S)-1,5, 13-trihydroxy-10-oxo-tridecyl] pyrrolidine (3). And broussonetines U and V were proposed to be (2S,3S,4S)-2-hydroxymethyl-3, 4-dihydroxy-5-(9-oxo-13-hydroxytridecyl)-5-pyrroline (4), (2R,3S,4R,5R)-2-hydroxymethyl-3,4-dihydroxy-5-[(E)-9-oxo-13-hydroxy-3-tridecenyl] pyrrolidine (5), respectively, by spectroscopic and chemical methods.     

Dechlorination of beta-methylallyl chloride by electrogenerated [Co(I)(bipyridine)3]+: an electrochemical study in the presence of cationic surfactants

We have investigated the electrocatalytic dehalogenation of beta-methylallyl chloride (beta-mAC), widely used in the polymer industry, using [Co(I)(bpy)3]+ (where bpy=2,2'-bipyridine) electrochemically generated in situ from [Co(II)(bpy)3]2+ at a glassy carbon electrode in the presence of three different cationic surfactants in aqueous solution. Cetyltrimethylammonium bromide (CTAB), tetradecyltrimethylammonium bromide (TDTAB), and cetylbenzyldimethylammonium chloride (CBDAC) were employed in the present investigation. The [Co(II)(bpy)3]2+-cationic surfactant systems show excellent electrocatalytic activity toward dehalogenation of beta-mAC. The dependence of the catalytic current, the corresponding potential, and the current function on the potential scan rate has been analyzed to assess the nature of the catalytic reaction. The second-order rate constant, kchem, for the reaction between the beta-mAC substrate and the electrogenerated-micelle stabilized-Co(I) complex has been calculated by a cyclic voltammetry technique. The reduction products after 3 h of bulk electrolysis have been identified by GC/MS to be one nonchloro compound (2-methyl-1,5-hexadiene (IV)) and two chloro compounds (1-chloro-2,5-dimethyl-2,5-hexadiene (V) and spiro[1.2]cylopropyl-6-chloro-5-methyl-hex-4-ene (VI)). Based on the electrochemical results and the mass spectral data, a reaction scheme involving all the reduction products has been proposed. Finally, a good correlation between the catalytic efficiency and the structural features of the surfactant molecules is demonstrated. The present study emphasizes the need for further optimization work to achieve maximum yield of nonchloro compound (IV) to employ the present [Co(II)(bpy)3]2+-cationic surfactant systems with a high catalytic efficiency as promising for possible applications.     

可见光催化氮杂环丙烯与马来酰亚胺的[3+2]环加成反应

本文报道了在可见光照射下,以10-甲基-9-均三甲苯基吖啶高氯酸盐为光催化剂,室温条件下实现了氮杂环丙烯与马来酰亚胺[3+2]环加成反应,以55-99%的产率合成了二氢吡咯[3,4-c]吡咯-1,3(2H,3aH)二酮类化合物。此外,向反应体系中加入DDQ,可一锅法得到芳构化的吡咯[3,4-c]吡咯-1,3(2H,5H)二酮。该方法具有操作简单、反应条件温、官能团耐受性好等特点。     

Gold‐Catalyzed Bicyclic Annulations of 2‐Alkynylbenzaldehydes with Vinyldiazo Carbonyls that Serve as Five‐atom Building Units

This work reports gold‐catalyzed bicyclic annulations of 2‐alkynyl‐1‐carbonylbenzenes with vinyldiazo ketones that serve as five‐atom building units. The importance of these reactions is to access 4,5‐dihydro‐benzo[g]indazoles, which form the structural cores of various bioactive molecules. According to our mechanistic analysis, we postulate initial [5+4]‐cycloadditions between benzopyrilium intermediates and vinyldiazo ketones, followed by 6‐π‐electrocyclizations to achieve the excellent stereoselectivity.     

Inclusion [2]complexes based on the cryptand/diquat recognition motif

Seven diquat-based inclusion [2]complexes were studied by proton NMR spectroscopy, electrospray ionization mass spectrometry, and X-ray analysis. The hosts used in these inclusion [2]complexes are bis(5-hydroxymethyl-1,3-phenylene)-32-crown-10, a bis(m-phenylene)-26-crown-8-based cryptand, and five bis(m-phenylene)-32-crown-10-based cryptands. Bis(m-phenylene)-32-crown-10-based cryptands have been proved to be able to complex diquat much more strongly than bis(m-phenylene)-32-crown-10 itself and one containing a pyridyl moiety has one of the highest K_a values reported to date. These hosts form 1:1 complexes with diquat in solution and in the solid state. It was found that the improved binding from bis(m-phenylene)-32-crown-10 to bis(5-hydroxymethyl-1,3-phenylene)-32-crown-10 was due to a supramolecular cryptand structure formed by chelation of the two terminal OH moieties of bis(5-hydroxymethyl-1,3-phenylene)-32-crown-10 with a water molecule as a hydrogen-bonding bridge.     

Initial members of the family of molecular mid-valent high-nuclearity iron nitrides: [Fe4N2X10]4- and [Fe10N8X12]5- (X = Cl-, Br-)

Current theoretical and experimental evidence points toward X = N as the identity of the interstitial atom in the [MoFe7S9X] core of the iron-molybdenum cofactor cluster of nitrogenase. This atom functions with mu6 bridging multiplicity to six iron atoms and, if it is nitrogen as nitride, raises a question as to the existence of a family of molecular iron nitrides of higher nuclearity than known dinuclear Fe(III,IV) species with linear [Fe-N-Fe]5+,4+ bridges. This matter has been initially examined by variation of reactant stoichiometry in the self-assembly systems [FeX4]1-/(Me3Sn)3N (X = Cl-, Br-) in acetonitrile. A 2:1 mol ratio affords [Fe4N2Cl10]4- (1), isolated as the Et4N+ salt (72%). This cluster has idealized C2h symmetry with a planar antiferromagnetically coupled [Fe(III)4(mu3-N)2]6+ core containing an Fe2N2 rhombus to which are attached two FeCl3 units. DFT calculations have been performed to determine the dominant magnetic exchange pathway. An 11:8 mol ratio leads to [Fe10N8Cl12]5- (3) as the Et4N+ salt (37%). The cluster possesses idealized D2h symmetry and is built of 15 edge- and vertex-shared rhomboids involving two mu3-N and six mu4-N bridging atoms, and incorporates two of the core units of 1. Four FeN2Cl2 and four FeN3Cl sites are tetrahedral and two FeN5 sites are trigonal pyramidal. The cluster is mixed-valence (9Fe(III) + Fe(IV)); a discrete Fe(IV) site was not detected by crystallography or M?ssbauer spectroscopy. The corresponding clusters [Fe4N2Br10]4- and [Fe10N8Br12]5- are isostructural with 1 and 3, respectively. Future research is directed toward defining the scope of the family of molecular iron nitrides.     

A convergent approach to the marine natural product eleutherobin: synthesis of key intermediates and attempts to produce the basic skeleton

Synthesis of (1R,5R,6R)-2-(6-hydroxymethyl-5-isopropyl-2-methylcyclohex-2-enyl)-N- methoxy-N-methylacetamide 8 from R-(-)-phellandrene in six steps, and (3aR*,4S*,6R*,6aS*)- (6-hydroxymethyl-4-methoxy-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol- 4-yl)acetic acid methyl ester 17 from tetrabromoacetone and 2-methoxy-5-methylfuran in six steps, provided two key fragments which have been combined to produce intermediates for attempted construction of the basic skeleton of eleutherobin.     

Efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines by a double annulation strategy from alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals

A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1] annulation strategy starting from easily available alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals 1 and cheap reagents (NH4OAc, DMF, and POCl3) has been developed. In the first step of the double annulation route, 2-amino-3-carbamoyl-5,6-dihydro-4-pyridones 2 were created in high to excellent yields by a formal [5C + 1N] annulation reaction of ketene-(S,S)-acetals 1 with ammonia (from ammonium acetate). In the second step of the double annulation strategy, the highly functionalized dihydropyrido[2,3-d]pyrimidine derivatives, 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones 3 (when R1 = aryl) and 7,8-dihydropyrido[2,3-d]pyrimidines 4 (when R1 = H), were constructed, respectively, in fair to good yields by reacting 2 with excessive Vilsmeier reagent (DMF/POCl3). A mechanism involved in the second [5 + 1] annulation step, including a formal [5 + 1] annulation and accompanied chlorovinylation, chloroformylation, amination, and aromatization reactions, is proposed.     

Synthesis of Urinary Metabolites of Retinoic Acid

Urinary metabolites 5-methyl-5-[2-(2,6,6-trimethyl -3-oxo-1-cyclohexen-1-yl)-vinyl]-2-tetrahydrofuranone (1) and 5-[2-(6-hydroxymethyl-2, 6-dimethyl-3-oxo-1- cyclohexen-1-yl)vinyl]-5-methyl-2-tetrahydrofuranone (2) of retinoic acid have been synthesized from 4-[2,2,6-trimethyl-3-(tetrahydro-2 H -pyran-2-yl)oxy-1-cyclohexen-1-yl]-3-buten-2-one (4) and methyl 2-(3,3-ethylenedioxy-1-butenyl)-1, 3-dimethyl-4-oxo-2-cyclohexene-1-carboxylate (5) .     

A New Type of Donor–Acceptor Cyclopropane Reactivity: The Generation of Formal 1,2‐ and 1,4‐Dipoles

A new type of donor–acceptor cyclopropane reactivity has been discovered. On treatment with anhydrous GaCl₃, they react as sources of even‐numbered 1,2‐ and 1,4‐dipoles instead of the classical odd‐numbered 1,3‐dipoles due to migration of positive charge from the benzyl center. This type of reactivity has been demonstrated for new reactions, namely, cyclodimerizations of donor–acceptor cyclopropanes that occur as [2+2]‐, [3+2]‐, [4+2]‐, [5+2]‐, [4+3]‐, and [5+4]‐annulations. The [4+2]‐annulation of 2‐arylcyclopropane‐1,1‐dicarboxylates to give polysubstituted 2‐aryltetralins has been developed in a preparative version that provides exceedingly high regio‐ and diastereoselectivity and high yields. The strategy for selective hetero‐combination of donor–acceptor cyclopropanes was also been developed. The mechanisms of the discovered reactions involving the formation of a comparatively stable 1,2‐ylide intermediate have been studied.