Synthesis, conformational analysis, and bioassay of 9,10-didehydroepothilone D

[reaction: see text] 9,10-Didehydroepothilone D was synthesized, its conformation was studied, and its tubulin polymerization and antiproliferative activity were compared with that of epothilone D and certain analogues.     

Die Kristallstrukturen von {Li3(12-Krone-4)2[HC(CN)2]3}, {Na(15-Krone-5)-[HC(CN)2]} und {Na[N(nBu)4][HC(CN)2]2 · THF}

The Crystal Structures of {Li₃(12-crown-4)₂[HC(CN)₂]₃}, {Na(15-crown-5)[HC(CN)₂]}, and {NaN(nBu)₄[HC(CN)₂]₂ · THF} The preparation and the crystal structures of the title compounds 1 — 3 are described. 1 forms a polymeric chain structure, in which one of the lithium ions is linked by Li…NCC(H)CN… bridges. The remaining lithium ions form (12-crown-4)Li[NCC(H)CN] units, which are coordinated by one of the nitrogen atoms of the dicyanomethanide ions with the lithium ions of the chain. 2 forms an ion pair, in which the sodium ion is coordinated by the five oxygen atoms of the crown ether molecule and by one nitrogen atom of the dicyanomethanide ion. 3 has a threedimensional network, in which the sodium ions are coordinated in a distorted tetrahedral manner by the nitrogen atoms of the dicyanomethanide ions. In the cavities of the network the tetrabutylammonium ions and the THF molecules are found.     

Tetrakis(triphenylphosphaniminato)titan, [Ti(NPPh3)4]

Tetrakis(triphenylphosphoraneiminato)titanium, [Ti(NPPh₃)₄] The title compound has been prepared by the reaction of [TiCl₂(NPPh₃)₂] with methyllithium and cyclopentadienyllithium, respectively, in hexane solution. [Ti(NPPh₃)₄] · 3 C₇H₈ crystallizes from toluene solution to form colourless, only slightly moisture sensitive crystals which were characterized by a crystal structure determination. Space group I4₁/a, Z = 8, lattice dimensions at ?80°C: a = b = 2160.7(2), c = 3334.2(3) pm, merohedral (110) twin, R = 0.077. The compound forms monomeric molecules with tetrahedrally coordinate titanium atoms and bonding parameters of TiN = 187.3 pm, PN = 155.1 pm, TiNP 150.4° in average.     

Asymmetric Synthesis of 3-Hydroxyprolines by Photocyclization of C(1′)-Substituted N-(2-Benzoylethyl)glycine Esters

The chiral N-(2-benzoylethyl)-N-tosylglycine esters 5a–h and the α-amino-γ-keto ester 6 were prepared from γ-(tosylamino) alcohols 7a–h . Irradiation of compounds 5a–c, e gave cis-3-hydroxyproline esters 20–23 (Scheme 6), partly with complete asymmetric induction by the C(1′)-substituent, whereas 6 gave enantiomerically pure 4-hydroxy-4-phenyl-L -proline esters 24 in good yield but low de (Scheme 6). The de of the photocyclization depended on the nature and/or size of the C(1′)-substituents. Irradiation of ketones 5d and 5f , bearing H-atoms at C(γ) with respect to the keto function, gave cyclobutanols (Scheme 9) in low yields besides the preferred Norrish-type-II cleavage product. Cyclopentanol 25 was a by-product of the photocyclization of 5c as a result of H? C(δ) abstraction from the t-Bu group. The structure of products 20, 22 , and 24a, b was established by NMR or X-ray analyses.     

High-pressure synthesis and crystal structure of silicon phosphate hydroxide, SiPO4(OH)

A new high-pressure phase, silicon phosphate hydroxide, was prepared at and 1000 °C in >98% purity. From X-ray diffraction on a pseudo-merohedrally twinned crystal, it was found that SiPO₄(OH) crystallizes in a monoclinic cell with space group P2₁/n (No. 14), , and Z=4. The refinement gave a conventional R_obs of 0.0320 and wR_obs of 0.0864 for the overlapped data from both twin components. In the structure, SiO₆ octahedra form chains along [101], with PO₄ tetrahedra alternating along the chain in the b-direction. The parallel chains link up with tetrahedral corners from other chains to form a 3-dimensional network. SiPO₄(OH) belongs to a structural family that includes HgSeO₄·H₂O. It is also related to the SbOPO₄ structure by a small distortion that lowers the symmetry from C2/c in SbOPO₄ to in SiPO₄(OH).     

Visualisation of the fibrillar and pore morphology of cellulosic fibres applying transmission electron microscopy

Applying transmission electron microscopy (TEM) on ultra-thin cross-sections of fibres, the main characteristics of the internal morphology of cotton and the main man-made cellulosic fibres (modal, viscose and lyocell) could be visualised. To obtain an appropriate contrast for TEM, isoprene was polymerised into the swollen fibres after a stepwise solvent exchange from water to acetone. The included polymer is stainable with osmium tetraoxide. Significant differences in distribution of pore sizes and pore arrangements in the cellulosic fibres were seen. Cotton showed very small pores in the bulk of the fibre, but drying cracks and flat pores between the sheets of the secondary wall appear as larger pores. Lyocell contains only nanopores in the bulk of the fibre with a slight gradient in pore density, and a very porous skin layer. In viscose and modal, a very wide pore size distribution from nanometer to micrometer size can be seen.     

Phosphonic-Acid Analogues of the N-Acetyl-2-deoxyneiiraniinic Acids: Synthesis and Inhibition of Vibrio cholerae Sialidase

The phosphonic acids 3 and 4 were prepared to compare their inhibitory activity on Vibrio cholerae sialidase with the one of the corresponding N-acetyl-2-deoxyneuraminic acids 5 and 6 . Thus, hydrogenation and benzylation of methyl N-acetyl-2,3-didehydro-2-deoxyneuraminate (1MeNeu2en5Ac; 7) gave a mixture of the fully O-benzylated benzyl and methyl esters 9 and 10 , the partially O-benzylated benzyl and methyl esters 11 and 12 , and the fully O-and N-benzylated benzyl and methyl esters 13 and 14 (Scheme 1). Transesterification of 9 to 10 and hydrolysis of 10 gave the acid 15 . Oxidative decarboxylation of 15 with Pb(OAc)₄ gave a 1:9 mixture of the α-and β-D-glycero-D-galacto-acetates 16 and 17 . Phosphonoylation of 17 with P(OMe)₃ and Me₃SiOTf gave a 1.3:1 mixture of the phosphonates 18 and 19 , which were deprotected to give the (4-acetamido-2,4-dideoxy-D-glycero-α-and β-D-galacto-octopyranosyl)phosphonic acids 3 and 4 , respectively. The acid 6 was obtained by epimerization of the tert-butyl ester 23 with lithium N-cyclohexylisoproylamide and deprotection. The phosphonic acids 3 (K_i 5.5 10_-5 M) and 4 (K_i 2.3.10^?4 M ) are stronger inhibitors of Vibrio cholerae sialidase than the anomeric N-acetyl-2-deoxyneuraminic acids 5 (K_i 2.3 10^?3 M ) and 6 . Both 3 and 4 inhibit the Vibrio cholerae sialidase, while only the carboxylic acid 5 , possessing an equatorial COOH group is an inhibitor.     

THE PHOTOPHYSICAL PROPERTIES OF PORPHYCENES: POTENTIAL PHOTODYNAMIC THERAPY AGENTS*

Porphycene and a tetra-n-propyl derivative remained unaltered on irradiation in toluene at room temperature. Quantum yields of fluorescence, S T intersystem crossing, and singlet molecular oxygen sensitization, as well as lifetimes of the singlet and triplet excited states were measured. In view of their structural relationship to porphyrin, their high absorption above 620 nm, their stability towards photooxidation, and their high quantum yields of fluorescence and singlet oxygen sensitization, these compounds qualify as potential agents for tumor marking and photodynamic therapy.