Clifford George

Synthesis of polyazapolycyclic caged polynitramines

Abstract Syntheses of new polyazapolycyclic caged polynitramines are described. Sequentially reacting 4,10-dibenzyl-2,6,8,12-tetraacetyl-2,4,6,8,10,12-hexaazaisowurtzitane (5a) with NOBF4 and NO2BF4 in sulfolane solvent produces 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazatetracyclo-[5.5.0.05,9.03,11]dodecane, 6). Syntheses of two new polyazapolycyclic caged trinitramines, 3,5,12-trinitro-3,5,12-triazawurtzitane (7a) and 2,4,10-trinitro-2,4,10-triazaadamantane (12a), as well as their labile parent secondary amines, are discussed. A new caged polynitrosamine, 3,5,12-trinitroso-3,5,12-triazawurtzitane (7d), has been obtained by ring-cleavage nitrosation of the new hexamine-wurtzitane compound 3,5,7,9-tetraazahexacyclo-[9.3.1.13,7.02,9.04,13.05,10]-hexadecane (10).

Iron(III) complexes of some thiosemicarbazones derived from 2-acetylpyridine, its 6-methyl derivative and itsN-oxide

SummaryA series of iron(III) complexes of thiosemicarbazones derived from 2-acetylpyridine, 6-methyl-2-acetylpyridine and 2-acetylpyridineN-oxide have been prepared from Fe(ClO4)3 and FeCl3. All of the isolated solids have cations involving two monobasic tridentate ligands, and either perchlorate or tetrachloroferrate(III) anions and are 1∶1 electrolytes. Coordinationvia the pyridine nitrogen (or theN-oxide oxygen), the imine nitrogen and the sulphur atom are confirmed by infrared spectra and x-ray diffraction. The presence of two different iron(III) species is indicated by the electron spin resonance spectra of the tetrachloroferrate(III) solids. E.s.r. along with electronic spectra prove the spin-paired configuration of these cationic iron(III) complexes.

Synthesis of Conformationally Restricted Carbocyclic Nucleosides: The Role of the O(4′)‐Atom in the Key Hydration Step of Adenosine Deaminase

Conformationally restricted carbocyclic nucleosides with either a northern(N)-type conformation, i.e., N-type 2′-deoxy-methanocarba-adenosine 8 ((N)MCdAdo), or a southern(S)-type conformation, i.e.S-type 2′-deoxy-methanocarba-adenosine 9, ((S)MCdAdo), were used as substrates for adenosine deaminase (ADA) to assess the enzymes preference for a fixed conformation relative to the flexible conformation represented by the carbocyclic nucleoside aristeromycin (10). Further comparison between the rates of deamination of these compounds with those of the two natural substrates adenosine (Ado; 1) and 2′-deoxyadenosine (dAdo; 2), as well as with that of the conformationally locked nucleoside LNA-Ado (11), which, like the natural substrates, has a furanose O(4′) atom, helped differentiate between the roles of the O(4′) anomeric effect and sugar conformation in controlling the rates of deamination by ADA. Differences in rates of deamination as large as 10000 can be attributed to the combined effect of the O(4′) atom and the enzymes preference for an N-type conformation. The hypothesis proposed is that ADAs preference for N-type substrates is not arbitrary; it is rather the direct consequence of the conformationally dependent O(4′) anomeric effect, which is more efficient in N-type conformers in promoting the formation of a covalent hydrate at the active site of the enzyme. The formation of a covalent hydrate at the active site of ADA precedes deamination. A new and efficient synthesis of the important carbobicyclic template 14a, a useful intermediate for the synthesis of (N)MCdAdo (8) and other conformationally restricted nucleosides, is also reported.

Synthesis, Conformational Analysis, and Biological Activity of a Rigid Carbocyclic Analogue of 2′-Deoxy Aristeromycin Built on a Bicyclo[3.1.0]hexane Template #

Abstract A new chiral synthesis of the pseudosugar synthon (1R,2S,4R,5S)-1-[(benzyloxy)methyl]-2-tert-butyloxy-4-hydroxybicyclo[3.1.0]hexane (12) is reported. This compound was used as a template for the construction of carbocyclic nucleoside 4, a conformationally rigid analogue of 2′-deoxyaristeromycin. The X-ray structure and 1H NMR analysis confirmed the exclusive North [2′-exo (2E)] conformation of 4 which is vastly different from that of other non-rigid carbocyclic nucleosides. Compound 4 showed good in vitro antiviral activity against human cytomegalovirus and EBV with minimal cytotoxicity. #This manuscript is dedicated to Professor Yoshihisa Mizuno on the occasion of his 75th birthday.

Electron Diffraction Investigation of Dimethyl Diselenide

The molecular structure of dimethyl diselenide has been determined by an electron diffraction investigation of the vapor. A computerized background correction routine, satisfying the positivity and area criteria, was employed to reduce the data and obtain a final molecular intensity curve. The values for a set of nine distances and amplitudes were obtained from a least‐squares fit to the final molecular intensity curve. The bonded distances are rg(C–H) = 1.131 ± 0.008 A, rg(C–Se) = 1.954 ± 0.005 A, and rg(Se–Se) = 2.326 ± 0.004 A. The corresponding amplitudes are l(C–H) = 0.079 ± 0.007 A, l(C–Se) = 0.054 ± 0.003 A, and l(Se–Se) = 0.056 ± 0.002 A. The ∠CSeSe = 98.9 ± 0.02° and the ∠HCSe = 108.4 ± 0.8°. The errors are estimated to be at the 99% confidence level. The methyl groups are unsymmetrically placed with respect to the CSeSe planes. They are rotated about the C–Se bonds such that one of the HCSe planes in each CH3Se moiety makes an angle of 36.1 ± 6° with the respective CSeSe plane. Dimethyl diseleni...

Determining the occurrence of a 3 10 -helix and an α-helix in two different segments of a lipopeptaibol antibiotic using TOAC, a nitroxide spin-labeled C α -tetrasubstituted α-aminoacid

Trichogin GA IV is a 11-residue lipopeptaibol antibiotic exhibiting membrane modifying properties. We synthesized step-by-step by solution methods three trichogin analogues, each with a double Aib (alpha-aminoisobutyric acid)-->TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) replacement. The strict similarity in the conformational propensities of Aib and TOAC allowed us to exploit these analogues in a detailed investigation of the conformation of this lipopeptaibol in different organic solvents and in a membrane-mimetic environment using in particular the double spin labeling ESR technique. We conclude that the secondary structure in solution remains essentially unchanged if compared to that previously found in the crystal state for trichogin. More specifically, the N-terminal region of the peptide folds in a 3(10)-helix, while the central and C-terminal regions are mainly alpha-helical. An additional, significant proof for the modest plasticity of the trichogin structure was obtained by an X-ray diffraction analysis of the nOct-[TOAC4,8, Leu-OMe11] analogue. For the three analogues permeability measurements revealed membrane-modifying properties comparable to those of natural trichogin.

Lithium dicyanamide, its reactions with cyanuric chloride, and the crystal structures of LiN(CN)2(MeCN)2 and LiCN(C5H5N)2

Abstract Reactions of dicyanamides with cyanuric chloride were investigated as possible routes to carbon nitrides. Anhydrous lithium dicyanamide (1) was synthesized from NaN(CN), and LiCl in THF. Compound 1 was found to react with cyanuric chloride to form a yellow product, which forms an amorphous lithium-carbon nitride with an approximate formula CN0.7Li0.2 upon thermolysis to 700°C. Upon heating to 1000°C, the product decomposes with the distillation of lithium cyanide. Reactions between cyanuric chloride and trimethylstannyl dicyanamide were also investigated. Lithium dicyanamide was also found to trimerize and polymerize at 280–320°C. Additionally, two LiCN complexes were structurally characterized. The bis (acetonitrile) adduct of 1 crystallizes with the lithium atoms linking the cyano nitrogens into infinite LiNCNCN chains, and the bis(pyridine) adduct of LiCN consists of infinite zig-zag LiCN chains.

aS,7S-absolute configuration of natural (−)-colchicine and allocongeners

The aS,7S‐absolute configuration of (−)‐colchicine (1) and (−)‐N‐acetylcolchinol methyl ether (3, NCME) suggested on the basis of 1H NMR data and negative Cotton effects at about 260 nm (EtOH) is firmly established by an X‐ray analysis of urea 5, a compound derived from 3. Binding of these compounds to tubulin requires an aS‐configuration of the biaryl system.

Estimation of the torsional potential for perfluorodi-methyl ether from electron-diffraction data

Abstract A structural model is obtained for perfluorodimethyl ether, based on the assumption of an equilibrium geometry with the effects of internal rotation appearing in the observed vibrational amplitudes. By separation of frame vibrations obtained from a spectroscopie force field, explicit formulae for calculating the torsional contributions from single and double rotors indicate a three-fold barrier height of 6.0 ± 1.5 kcal mol −1 . With this barrier height, the observed torsional displacement away from the COC equilibrium plane is found to be a significant feature of the model.

Crystallographic structure of a helical lipopeptaibol antibiotic analogue

An X-ray diffraction analysis of the [Fmoc0, TOAC4,8, Leu-OMe11]analogue of the lipopeptaibol antibiotic trichogin A Iv shows that the undecapeptide is folded in a right-handed, mixed α/310-helix. The helical molecules are connected in a head-to-tail arrangement along the b-axis through C=O...H-N intermolecular H-bonding. This packing mode generates a hydrophobic cavity where the Fmoc Nα-protecting groups are accommodated. The distances and angles between the nitroxide groups of the two TOAC residues, separated by one turn of the α-helix, have been determined.