Synthesis of mono- and polyhydroxylated cyclobutane nucleoside analogs

Enantiomerically enriched cyclobutene compounds 13 and 24 are good precursors of several cyclobutane nucleoside analogs. The synthetic ways involve, in the key step, either hydroboration or dihydroxylation.     

Sanglifehrin-cyclophilin interaction: degradation work,synthetic macrocyclic analogues,X-ray crystal structure,and binding data

Sanglifehrin A (SFA) is a novel immunosuppressive natural product isolated from Streptomyces sp. A92-308110. SFA has a very strong affinity for cyclophilin A (IC(50) = 6.9 +/- 0.9 nM) but is structurally different from cyclosporin A (CsA) and exerts its immunosuppressive activity via a novel mechanism. SFA has a complex molecular structure consisting of a 22-membered macrocycle, bearing in position 23 a nine-carbon tether terminated by a highly substituted spirobicyclic moiety. Selective oxidative cleavage of the C(26)=C(27) exocyclic double bond affords the spirolactam containing fragment 1 and macrolide 2. The affinity of 2 for cyclophilin (IC(50) = 29 +/- 2.1 nM) is essentially identical to SFA, which indicates that the interaction between SFA and cyclophilin A is mediated exclusively by the macrocyclic portion of the molecule. This observation was confirmed by the X-ray crystal structure resolved at 2.1 A of cyclophilin A complexed to macrolide 16, a close analogue of 2. The X-ray crystal structure showed that macrolide 16 binds to the same deep hydrophobic pocket of cyclophilin A as CsA. Additional valuable details of the structure-activity relationship were obtained by two different chemical approaches: (1) degradation work on macrolide 2 or (2) synthesis of a library of macrolide analogues using the ring-closing metathesis reaction as the key step. Altogether, it appears that the complex macrocyclic fragment of SFA is a highly optimized combination of multiple functionalities including an (E,E)-diene, a short polypropionate fragment, and an unusual tripeptide unit, which together provide an extremely strong affinity for cyclophilin A.     

A quantum-mechanical study of the interaction of methylglyoxal with guanine

Ab initio self-consistent field molecular orbital computations on the relative stabilities of the different possible intermediate adducts for the reactions between methylglyoxal and guanine, as well as the evaluation of the relative stabilities of the two different possible final cyclic products (IIIb and IIIc) point all to the conclusion that it is the addition product in which the methyl group is close to the amino nitrogen which is the most stable one.     

Synthesis of BILN 2061, an HCV NS3 protease inhibitor with proven antiviral effect in humans

The synthesis of BILN 2061, an NS3 protease inhibitor with proven antiviral effect in humans, was accomplished in a convergent manner from four building blocks. The procedure described here was suitable for the preparation of multigram quantities of BILN 2061 for preclinical pharmacological evaluation.     

The two-photon excitation spectrum of triphenylene in n-heptane single crystals

A comparison of the one-and two-photon absorption spectra of triphenylene in n-heptane single crystals at 1.6. K reveals that the lowest singlet state (S₁) is of ¹A′₁ symmetry while the second singlet state(S₂) has ¹A′₂ symmetry, in contradiction with the commonly accepted assignment.     

Ab initio studies of arginine and deaminoarginine

L-Arginine and Deaminoarginine were studied via quantum chemical ab initio calculations using the STO -3G basis set for arginine and the STO -3G and 3–21G basis sets for deaminoarginine. It was found that the most stable conformations are the ones featuring the carboxyl group slightly twisted versus the rest of the molecule, which adopts an extended conformation. It was also found that the cyclic zwitterion is less stable than the neutral cyclic conformation and that there is a barrier to the proton transfer from the carboxyl's oxygen to one of guanidine moiety's nitrogens.     

Self-assembly of water-soluble dendrimers into thermoreversible hydrogels and macroscopic fibers

Hydrogels and macroscopic fibers are formed through the salt-induced self-assembly of water-soluble polycationic phosphorus dendrimers. Interestingly, the hydrogels are thermoreversible and the sol-gel transition temperature can be easily tuned in a wide range of temperatures (approximately 2-80 degrees C). The effects of different parameters, such as salt nature, dendrimer generation, concentration, and temperature, on dendrimer aggregation are examined. The macroscopic fibers are prepared by flocculation under flow and observed using scanning electron microscopy (SEM) which reveals a microscopic fibrillar substructure. We interpret the gelation and flocculation of the polycationic dendrimers in terms of colloidal flocculation.     

Preparation and resolution of a modular class of axially chiral quinazoline-containing ligands and their application in asymmetric rhodium-catalyzed olefin hydroboration

The preparation and resolution of a series of axially chiral quinazoline-containing ligands is described in which the key steps are the metal-catalyzed naphthyl-phosphorus bond formation, the naphthalene-quinazoline Suzuki coupling, and the preparation of the Suzuki electrophilic components from the corresponding imidate and anthranilic acid. Diastereomeric palladacycles derived from the racemic phosphinamines and (+)-di-mu-chlorobis[(R)-dimethyl(1-(1-naphthyl)ethyl)aminato-C2,N]dipalladium(II) were separated by fractional crystallization. The configuration of the resulting diastereomers was determined by X-ray crystallographic analysis. Displacement of the resolving agent by reaction with 1,2-bis(diphenylphosphino)ethane afforded enantiopure ligand in each case. Their rhodium complexes were prepared and applied in the enantioselective hydroboration of a range of vinylarenes. The quinazolinap catalysts were found to be extremely active, giving excellent conversions, good to complete regioselectivities, and the highest enantioselectivities obtained to date for several members of the vinylarene class, including cis-beta-methylstyrene (97%), cis-stilbene (99%), and indene (99.5%).     

Cooperative recognition of C60-ammonium substrates by a ditopic oligophenylenevinylene/crown ether host

A new fullerene derivative with an ammonium subunit has been prepared. Its ability to form supramolecular complexes with oligophenylenevinylene derivatives bearing one or two crown ether moieties has been evidenced by electrospray mass spectrometry, and UV-visible and luminescence spectroscopy experiments. Interestingly, the assembly of the C60-ammonium cation with the oligophenylenevinylene derivative bearing two crown ether moieties leads to the cooperative formation of the 2:1 complex owing to intramolecular fullerene-fullerene interactions.     

Supramolecular click chemistry for the self-assembly of a stable Zn(II)-porphyrin-C60 conjugate

Owing to the complementarity between a bis-Zn(II)-porphyrin receptor and a fullerene ligand bearing two pyridine substituents, the substrate can be clicked onto the ditopic receptor, thus leading to a stable non-covalent macrocyclic 1 ratio 1 complex.