Synthesis of benzofuran derivatives—II A new synthesis of visnagin

Starting with 2-methyl-5:7-dihydroxychromone, an allyl group is introduced into the 6-position by Claisen migration of a 5-allyl ether. The initial protection of the 7-hydroxyl is best effected by tosylation. If the tosyl group is removed before Claisen migration and the C-allyl compound subjected to ozonolysis and ring closure, norvisnagin is obtained in a poor yield and can be methylated to visnagin. In an alternative method the tosyl group is removed just before ozonolysis. For this purpose the previous methylation of the 5-position is advantageous. This route gives visnagin directly in good yield.     

Unconventional nucleotide analogues—XVIII: Ring expansion of uridine halocarbene adducts. Synthesis of diazepine nucleosides

The diastereomeric adducts of dichlorocarbene and dibromocarbene with (protected) uridine react with alcohols to give diazepine nucleosides (4a–c). The endo-chloro-exo-fluorocarbene adducts (1d and 2d) also react analogously to yield diazepine nucleoside 4d. On the other hand, the corresponding exo-chloro-endo-fluoro isomers (1e and 2e) are totally inert under the same reaction conditions. The adducts 1b and 2b yield, besides the ring-expanded product (4b), uridine-5-aldehyde (6a) in varying amounts which depend upon the conformation of the diastereomer. These results are explained on the basis of a possible role of the ring-oxygen of the ribose moiety.     

Reactions of acylarylnitrosamines—II

Decomposition of acylarylnitrosamines in benzene produces not only free radicals as is well recognized, but also intermediate ion pairs. The generality of this dual mechanism is experimentally demonstrated by use of nucleophilically activated fluorine as a ‘label’. The appearance of acylfluoride in the reaction products from fluorine substituted acylarylnitrosamines is interpreted.     

Haschisch—Xi Massenspektrometrische bestimmung von haschisch-inhaltsstoffen—II

The fragmentation of cannabidiol dimethylether and related compounds has been investigated by means of deuterium labelling and model compounds. The most important fragmentation processes start with a retro-Diels-Alder reaction of the cyclohexene ring, principally witout migration of the double bond. With certain ions an unusual -cleavage of the n-pentyl and methoxy substituents of the phenyl ring has been observed.

All known double bond isomers of the tetrahydrocannabinol type have been identified with certainty by means of their mass spectra.     

Synthesis of a ‘twisted’ transition-state analogue of biotin

A facile, racemic synthesis of a ‘twisted’ transition-state analogue of biotin is described. A key reaction is the electronically assisted ring-closure of the sulfur containing ring by displacement of an in situ generated mesylate by a suitably positioned 4-methoxybenzyl sulfide. The crystal structure of tricyclic compound 6 shows the AB ring system to indeed be twisted. The ‘twist’ was introduced to examine the possible involvement of sulfur participation in biotin biochemistry.     

Inclusion complexes of a nucleotide analogue with hydroxypropyl-beta-cyclodextrin

Bis(tbutyl-S-acyl-2-thioethyl)-AraCMP (UA911) is a mononucleotide prodrug developed to overcome some of the cellular resistance to cytotoxic deoxynucleosides analogues. Its use for in vivo studies is limited due to its poor solubility in water. Thus, 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) was proposed to solubilize UA911 in water, in order to obtain concentrations needed for in vivo experiments. A molar ratio of HP-β-CD: UA911 of 3:1 was sufficient to obtain complete solubilization of the prodrug. The corresponding inclusion complex was characterized by differential scanning calorimetry and ¹H NMR spectroscopy study provided a definitive proof of the formation of the inclusion complex. The complex retained its cytotoxic activity as shown by in vitro cell survival assays on murine leukemia cells, and was evaluated in vivo. HP-β-CD is therefore suitable for the preparation of adequate solutions for the study of the antitumoral activity of nucleotide prodrugs such as UA911.     

Asymmetric annellation effects—II

The comparison of the U.V. absorption spectra of acenes, 1:2–3:4-dibenzacenes and tetrabenzacenes shows a strong asymmetric annellation effect. This is explained on the basic assumption that an aromatic sextet or benzenoid ring can transfer only two electrons to another ring. Three benzenoid rings can thus produce an induced aromatic sextet in an included ring of the type of the central ring in triphenylene.

The synthesis of tetrabenzotetracene is described.     

Unconventional nucleotide analogues—XVII: Ring-transformations of uracil dihalocarbene adducts

Halocarbene adducts of 1,3-disubstituted uracil (3a, b, d) undergo ring-enlargement to yield 1,3-diazepine derivatives (4a–d). The ring-opening of the cyclopropane system is controlled by the stereochemical configuration of the halogen atom, which can be eliminated as a halide ion. Reduction of the adducts with n-Bu₃SnH leads to a variety of 1,3-diazepines. Details of the mechanism of formation of the diazepines and their further transformations are discussed.     

Synthesis of dysiherbaine analogue

Synthesis of dysiherbaine analogue 4, which corresponds to 8,9-epi-neodysiherbaine A, is described. The synthesis features a concise route to the bicyclic ether skeleton through stereoselective C-glycosylation to set the C₆ stereocenter and 5-exo ring-closure to form the tetrahydrofuran ring. The results of preliminary biological studies of 4 are also provided.     

Cyanidosilicates—Synthesis and Structure

Starting from fluoridosilicate precursors in neat cyanotrimethylsilane, Me₃Si?CN, a series of different ammonium salts [R₃NMe]⁺ (R=Et, ⁿPr, ⁿBu) with the novel [SiF(CN)₅]^2? and [Si(CN)₆]^2? dianions was synthesized in facile, temperature controlled F^?/CN^? exchange reactions. Utilizing decomposable, non‐innocent cations, such as [R₃NH]⁺, it was possible to generate metal salts of the type M₂[Si(CN)₆] (M⁺=Li⁺, K⁺) via neutralization reactions with the corresponding metal hydroxides. The ionic liquid [BMIm]₂[Si(CN)₆] (m.p.=72 °C, BMIm=1‐butyl‐3‐methylimidazolium) was obtained by a salt metathesis reaction. All the synthesized salts could be isolated in good yields and were fully characterized.     

Unconventional nucleotide analogues: Reaction of carbenes with uracil and uridine derivatives

Carbenes 2a-d (:CCl₂, :CBr₂, :CFC1, :CHCOOC₂H₅) add to the 5,6-double bond of uracil derivatives la-e to give adducts in modest to good yields The unsymmetrically substituted carbenes :CFC1 2c and CHCOOC₂H₅, 2d lead, as expected, to the formation of mixtures of endo and exo-isomers 3c-n which were separated and identified via their ¹H NMR spectra. Reaction of 2d with pyrimidine derivatives 5a,b resulted in products which can be rationalized in terms of addition at either the 5,6 or the 3,4 double bond. Addition of carbenes 2a-c to uridine derivatives gave diastereomeric adducts 12-16 which were isolated and identified. The two diastereomeric series, referred to as A and B, have been correlated and assigned the configurations 5S, 6S and 5R, 6R, respectively, on the basis of X-ray structure analysis of 12B The adducts of 2a,c and the uridine derivatives 11a,b have been deprotected to give 7,7-dihalocyclothymidines.     

Thermodynamique des complexes metalliques ternaires des amino-acides. II. Etude des systemes Ni(II)—glycine—valine Ni(II)—alanine—valine

Standard enthalpies and entropies of formation for binary and ternary Ni(II) complexes with pairs of the following amino acids as ligands: glycine, DL--alanine and DL-valine, were calorimetrically determined at 25°C in aqueous solution using 1 M ionic strength (NaClO₄).

The results are discussed according to every possible pathway for mixed ligand complex formation and also using the classical statistical methods. Temperature-dependent and temperature-independent components of the thermodynamic data are calculated. In all cases with these ligands involving identical coordination sites, the temperature-independent component of the enthalpy change is closely constant for binary as well as for ternary complexes. All the data show that the stabilization of mixed ligand complexes with respect to the parent binary complexes arises from the entropy term and is maximum for the Ni(II)—glycine—valine system.     

Zur nomenklatur der phane—II

The new term “Phanes” has been clearly defined and a nomenclature system tentatively developed. This system is comprehensible and of general application and at the same time relatively simple. The notations “nucleus”, “bridge”, “number of bridge members” and “number of ring members” are defined. In order to get a definite characterisation of the phanes which contain a carbocyclic nucleus, a carbocyclic and heterocyclic bridge the following terms: “carbophanes”, “carba-phanes” and “hetera-phanes” have been newly introduced. The prefix “hetera-” has been proposed as a general expression and as a representative term for the syllables “aza-”, “oxa-”, “thia-” and so on. The so called “a-nomenclature” is clearly called “hetera-nomenclature”. The new expressions “heteralogous” and “substitulogous” are explained. As the various examples will show, the “Phane-Nomenclature” can also be applied to the naming of complicated metallocenophanes.     

Hindered rotation in thioamides—II

The NMR spectra for a series of amides and thioamides of type where R = CH₃, C₆H₅ and C₆H₅CH₂, were investigated from ?60° to 150°C. The Arrhenius activation energies, E_a, for the normal amide equilibration were determined by the W_½ method and the values range from 15.4 to 20.9 Kcal/mole. The three thioamides, compounds ( 2 ), ( 4 ) and ( 6 ) yield spectra showing a second, low temperature, equilibration. This exchange was first studied by Siddall and co-workers and they interpreted the spectral changes in terms of population changes of the conformational isomers about the N? CH bonds. They assumed strong interaction of nitrogen alkyl groups which gave rise to three low energy dl pairs of isomers. Their results, however, as well as those obtained for similar compounds reported herein, show only two sets of patterns at low temperatures. These spectra suggest a first order, A?B, type equilibration where P_A≠P_B. An alternative assignment based upon the following classification of steric effects of S, R, R′ and R″, is suggested; (1) a strong interaction of the sulfur atom with the adjacent alkyl group on the nitrogen atom, R′, (2) a somewhat weaker interaction of R with the adjacent nitrogen alkyl group R″ and (3) a still weaker interaction of the two nitrogen alkyl groups, R′ and R″. This leads to four isomers, two dl pairs, C₁T₄, C₆T₃ and C₁T₆, C₆T₃, which are expected to have a lower energy than the rest and the first pair is preferred. The W_½ method of measuring exchange rates was extended to cover A?B equilibrations, where P_A≠P_B. The results indicate an accuracy that is not significantly lower than that obtained by the more elaborate total line shape analysis.     

Unconventional consideration of the symmetry properties—New techniques and computer codes: Application for high‐temperature superconductors

The conventional technique for solving the equations of quantum chemistry is extended to the structures possessing certain symmetries. This proposal allows the release of unoccupied electronic states located lower than the ground‐state Fermi level of a specific system. Such states can be treated as “spectral holes.” Application of this technique, in particular, when calculating the electronic structure of the high‐temperature superconductor (HTSC) compound YBa₂Cu₃O_{7? δ} (0 ≤ δ ≤ 1) results in the following. For all versions of the examined charge distributions over a crystal lattice, spectral holes of high spatial localization are found. The “spatial spectral holes” are located mainly at the p_y‐orbitals of the apex oxygens. These orbitals overlap and form linear chains that are parallel to the known Cu(1)? O chains, disappearing when δ is close to 1. One can suppose that the linear chains of the overlapping hole states form a “superconducting channel.” Some other parameters closely related to the critical characteristics of HTSC materials are also calculated. The calculations show that the superconducting channel is broken when the oxygen chain atoms O(1) are removed (δ > 0). © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002     

Structural investigation of lac resin—II

The three fractions of lac rein viz., hard resin I, hard resin II and soft resin have been cleaved with hydriodic acid followed by deiodination. The products were separated into fatty acids and terpene acids. The former have been studied by GLC and data on the nature and distribution of the chain lengths and their relative amounts were thus obtained. Cleavage of the different fractions of the resin with hydrogen chloride followed by alkaline hydrolysis gave the total aleuritic acid quantitatively. Based on the above results, the possibility of the presence of alkali stable linkages in lac resin and the amount of aleuritic acid liberated only by acid cleavage have been determined.