Isolation,chemical characterization and structure of ansamitocin,a new antitumor ansamycin antibiotic

In this paper we report the isolation, chemical characterization and structural elucidation of Ansamitocin, a new antitumor antibiotic obtained from Nocardia No. C-15003 (N-1). Ansamitocin P-3, P-3' and P-4 with molecular formulae C₃₂H₄₃ClN₂O₉, C₃₂H₄₃ClN₂O₉ and C₃₃H₄₅ClN₂O₉, respectively, were identified as novel antibiotics. Their UV spectra resemble that of maytansine obtained from a plant source. Analysis of the PMR spectrum and spin-decoup studies of P-3 demonstrated that its skeletal structure was the same as that of maytansine. Reductive cleavage of each antibiotic gave maytansinol (P-0). Alkali hydrolysis of P-3, P-3' and P-4 gave isobutyric, butyric and isovaleric acids, respectively. P-3, P-3' and P-4 were concluded to be the isobutyrate, butyrate and isovalerate ester of maytansinol at C-3, respectively. An antitumor plant product, maytanacine, and its semisynthetic derivative, maytansinol propionate, were also produced by the same strain.     

The role of the solvent in equilibrium and kinetic aspects of metal chelate extractions

Equilibria and kinetics for the extraction of nickel(II) and copper(II) by 2-hydroxy-5-nonylbenzophenone oxime (LIX 65N) in seven organic solvent systems were studied in order to test the validity of several hypotheses related to the role of the solvent in equilibrium and kinetic aspects of metal chelate extraction. For the nickel—LIX 65N system, the extraction constant is essentially independent of the solvent system, whereas for the copper—LIX 65N system, the extraction constant is not independent of solvent; this indicates that while the stoichiometry of the nickel chelate remains the same in all solvents, that of copper does not. The observed rate constant for the nickel—LIX 65N extraction was found to vary inversely with the LIX 65N distribution constant as predicted from a mechanism involving slow formation of the 1:1 complex. The observed reaction rate constant for the copper—LIX 65N varied inversely with the square of the distribution constant, also in accordance with the previously postulated mechanism of the slow formation of the 2:1 copper complex. This study, therefore, unequivocally eliminates the interfacial mechanism in favor of the homogeneous chemical reaction mechanism for the extraction of metal ions by LIX 65N, as well as by other similar high-molecular-weight extractants.     

Cover Picture

The cover picture shows a section of the electron charge density of the first metal carbide endohedral metallofullerene (Sc(2)C(2))@C(84) obtained from a synchrotron X-ray powder diffraction study by the maximum entropy method (MEM). The several density maxima, which correspond to scandium and carbon atoms, are clearly seen inside the C(84) carbon cage. The MEM charge density distribution also reveals that the C(84) cage has D(2d) symmetry (no. 23) and that the C(2) axis is parallel to the <100> face-centered cubic (fcc) direction of the unit cell. As a consequence of the site symmetry being 4mm, the C(2) axis of (Sc(2)C(2))@C(84) is oriented to six equivalent <100> directions and shows a merohedral disorder. The resultant Sc small middle dot small middle dot small middle dotSc distances and C-C bond lengths of the Sc(2)C(2) cluster are 0.429(2) and 0.142(6) nm, respectively. The observed C-C bond length is between that of a typical single and a double bond, and is very close to that of the C-C bond (0.143 nm) combining two pentagons in a C(60) molecule. More about this fascinating structure can be found in the contribution by Shinohara and co-workers on p. 397 ff.     

Long-range magnetic ordering of quasi-one-dimensional S=1/2 Heisenberg antiferromagnet Sr2Cu(PO4)2

Magnetic properties of quasi-one-dimensional S=1/2 Heisenberg antiferromagnet Sr₂Cu(PO₄)₂ were investigated by temperature and field dependence of AC susceptibility down to 0.03 K. A sharp peak was observed at on the temperature dependence of AC susceptibility indicating long-range magnetic ordering. Taking into account the exchange constant, (Hamiltonian =J∑S_iS_i+1), the ratio k_BT_N/J is 0.06%. Sr₂Cu(PO₄)₂ is, therefore, one of the best one-dimensional Heisenberg antiferromagnet known so far.     

Metal-induced supramolecualr chirality in an optically active polythiophene aggregate

Chiral polythiophenes (PTs), in sharp contrast to other optically active polymers, exhibit optical activity in the pi-pi* transition region which is derived from the chirality of the main chain when they self-assemble to form a supramolecular pi-stacked aggregate with intermolecular interactions in a poor solvent or in a film. We now report that the regioregular, optically active PT poly[(R)-3-[4-(4-ethyl-2-oxazolin-2-yl)phenyl]thiophene] (poly-1) exhibits unique split-type induced circular dichroism (ICD) in the pi-pi* transition region of the main chain upon complexation with various metal salts such as trifluoromethanesulfonates of copper(I), copper(II), silver(I), and zinc(II), and iron(II) perchlorate in chloroform, which is a good solvent for poly-1. The appearance of ICD and slight changes in the UV/Vis spectra (no color change), except for the zinc salts, indicated that the chirality may not be induced by chiral pi-stacked aggregates of poly-1, but by the chirality of the main chain, for example, a predominantly one-handed helical structure induced by intermolecular coordination of the oxazoline groups to metal ions. The sign of the Cotton effect depends on the metal salt; most metal salts induced ICDs with similar Cotton-effect patterns, while zinc salts caused an inversion of the signs of the Cotton effect of poly-1 accompanied by a gradual red shift in the absorption of up to 125 nm. The changes in the conformation and the size of the poly-1 aggregates induced by different metal salts were also investigated by (1)H NMR titrations, static light scattering (SLS), atomic force microscopy (AFM), and membrane filtration. On the basis of these results, we propose a possible model for the chiral supramolecular aggregates of poly-1 with metal salts.     

Novel pyridinium salts as cationic thermal and photoinitiators and their photosensitization properties

Novel pyridinium salts [N‐(α‐phenylbenzyl)‐, N‐(1‐naphthylmethyl)‐, or N‐cinnamyl p‐ or o‐cyanopyridinium hexafluoroantimonates] were synthesized by the reaction of p‐ or o‐cyanopyridine and the corresponding bromides followed by anion exchange with KSbF₆. These pyridinium salts polymerized epoxy monomers at lower temperatures than previously reported for N‐benzyl‐2‐cyanopyridinium hexafluoroantimonate. The o‐substituted pyridinium salts showed higher activity than the p‐substituted ones, and the crosslinked epoxy polymers cured with these initiators showed higher glass‐transition temperatures. These pyridinium salts photoinitiated radical polymerization as well as cationic polymerization. The photopolymerization was accelerated by the addition of aromatic ketones as photosensitizers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1037–1046, 2002     

IMMUNOLOGICALLY ACTIVE LESIONS INDUCED ON DOUBLE-STRANDED DNA WITH ULTRAVIOLET

Abstract— Some immunochemical properties of double-stranded DNA irradiated with UV were studied, using a radioimmunoassay with irradiated [³H]-DNA and experimentally produced antibodies to DNA. Reactivity of antibodies revealed that irradiated DNA contained an immunologically active structure other than the irradiated DNA specific structure, resembling that of thermally denatured DNA. inhibition assay demonstrated that while DNA-antibody binding was effectively inhibited by mixed purine and pyrimidine oligonucleotides, thymine dimer containing pyrimidine oligonucleotides derived from the irradiated DNA showed no appreciable inhibition. The antigenic structure specific for irradiated DNA was found to be thermally labile in low salt medium. Cupric and ferrous ions and cysteine added to the DNA solution inhibited antigenicity formation during irradiation, but these substances exhibited no effect on dimer formation in irradiated frozen thymine solution. Calcium ions and histidine were inert for the former reaction but inhibited the latter effectively. This suggests that different mechanisms are involved in the 2 processes. The immunologically active UV-induced lesions appeared to depend mainly on a conformational structure change of the DNA strands rather than on a single modified base moiety.     

Syntheses and structures of hypervalent pentacoordinate carbon and boron compounds bearing an anthracene skeleton--elucidation of hypervalent interaction based on X-ray analysis and DFT calculation

Pentacoordinate and tetracoordinate carbon and boron compounds (27, 38, 50-52, 56-61) bearing an anthracene skeleton with two oxygen or nitrogen atoms at the 1,8-positions were synthesized by the use of four newly synthesized tridentate ligand precursors. Several carbon and boron compounds were characterized by X-ray crystallographic analysis, showing that compounds 27, 56-59 bearing an oxygen-donating anthracene skeleton had a trigonal bipyramidal (TBP) pentacoordinate structure with relatively long apical distances (ca. 2.38-2.46 A). Despite the relatively long apical distances, DFT calculation of carbon species 27 and boron species 56 and experimental accurate X-ray electron density distribution analysis of 56 supported the existence of the apical hypervalent bond even though the nature of the hypervalent interaction between the central carbon (or boron) and the donating oxygen atom was relatively weak and ionic. On the other hand, X-ray analysis of compounds 50-52 bearing a nitrogen-donating anthracene skeleton showed unsymmetrical tetracoordinate carbon or boron atom with coordination by only one of the two nitrogen-donating groups. It is interesting to note that, with an oxygen-donating skeleton, the compound 61 having two chlorine atoms on the central boron atom showed a tetracoordinate structure, although the corresponding compound 60 with two fluorine atoms showed a pentacoordinate structure. The B-O distances (av 2.29 A) in 60 were relatively short in comparison with those (av 2.44 A) in 59 having two methoxy groups on the central boron atom, indicating that the B-O interaction became stronger due to the electron-withdrawing nature of the fluorine atoms.     

Catalytic specificity exhibited by p-sulfonatocalix[n]arenes in the methanolysis of N-acetyl-l-amino acids

Specific acid catalysis of p-sulfonatocalix[n]arenes (n = 4, Calix-S4; n = 6, Calix-S6; n = 8, Calix-S8) was observed in the alcoholysis of N-acetyl-l-amino acids in methanol. The methanolysis rates of basic amino acid substrates (His, Lys, and Arg) were markedly enhanced in the presence of Calix-Sn, as compared with rates observed with p-hydroxybenzenesulfonic acid (pHBS), which is a noncyclic analogue of Calix-Sn. This catalytic effect of Calix-Sn was not observed for the methanolysis of Phe, Tyr, and Trp substrates. On the other hand, (1)H NMR experiments following the effect of Calix-Sn on N-acetyl-l-amino acid substrates in CD(3)OD showed that the spectrum of a mixture of the His substrate with Calix-Sn was significantly different from the combined spectra of the respective compounds. These changes in spectra support the formation of an inclusion complex of Calix-Sn with basic amino acids. Furthermore, it was obvious that methanolysis of the His substrate catalyzed by Calix-S4 and Calix-S6 obeyed Michaelis-Menten kinetics. These results indicate that the catalytic activity of Calix-Sn originates from its forming a complex with specific substrates (basic amino acids), similar to enzymatic reactions.     

Synthesis of a novel potential tridentate anthracene ligand, 1,8-bis(dimethylamino)-9-bromoanthracene,and its application as chelate ligand for synthesis of the corresponding boron and palladium compounds

A novel potential tridentate ligand, 1,8-bis(dimethylamino)-9-bromoanthracene, was synthesized. The key steps are as follows: 1) dimethylamination of 1,8-dibromo-9-methoxyanthracene by a modified Buchwald's method to afford 1,8-bis(dimethylamino)-9-methoxyanthracene, and 2) reduction of the methoxy group by LDBB (lithium di-tert-butylbiphenylide) followed by treatment with BrCF2CF2Br. The corresponding 1,8-bis(dimethylamino)-9-lithioanthracene, which should be a useful versatile tridentate ligand, could be generated by treatment of the bromide with one equivalent of nBuLi. The lithioanthracene reacted with B-chloroborane derivatives to give three 9-boryl derivatives. Although we recently reported that the crystal structure of 1,8-dimethoxy-9-B-catecholateborylanthracene was a symmetrical compound with the almost identical two O-B distances (2.379(2) and 2.441(2) A), the newly prepared 1,8-bis(dimethylamino)-9-borylanthracene derivatives clearly have unsymmetrical structures with coordination of only one NMe2 group toward the central boron atom. However, the energy difference between the unsymmetrical and symmeterical structures was found to be very small based on 1H NMR measurements, in which symmetrical anthracene patterns in the aromatic region (two kinds of doublets and a triplet) and a sharp singlet signal of the two NMe2 groups were observed even at -80 degrees C. 1,8-Bis(dimethylamino)-9-bromoanthracene itself can be a versatile ligand for transition metal compounds. In fact, direct palladation of the bromide took place by the reaction with [Pd2(dba)3].CHCl3 in THF to give the 9-palladated product. X-ray crystallographic analysis of the Pd compound showed that the square planar palladium atom was coordinated in a symmetrical fashion by both NMe2 groups (Pd-N bonds are 2.138(5) and 2.146(5) A).