Chemical modification of an antitumor alkaloid camptothecin: synthesis and antitumor activity of 7-C-substituted camptothecins.

A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl- (4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.     

Transition of nylon 6 γ-phase crystals by stretching in the chain direction

A crystal transition was found in nylon 6 fibers from the γ-phase to α-phase on stretching in the chain direction. The γ-phase fiber prepared by iodine treatment was stretched under constant load and the crystal deformation was observed by an x-ray method. The critical stress for the transition was estimated as 4 × 10³ kg./cm.² at room temperature. For this crystal transition the following conditions must be satisfied: (1) extension of the γ-phase chain to untwist the chain around the amide groups, (2) translational mobility of the chain to change the stacking in the crystallite. At the critical stress, the chain in the crystal is extended to nearly the same length as that of α-phase. The translational movement occurs under stress higher than about 3 × 10³ kg./cm.², and the pseudohexagonal cell is deformed into a monoclinic form. However, the monoclinic crystallites present at a stress lower than the critical value estimated above are unstable and may be brought back to the original form by head treatment at 100°C. No crystal transition occurs at low temperature.     

Dynamics and mechanisms of the multiphoton gated photochromic reaction of diarylethene derivatives

The cycloreversion (ring-opening) process of one of the photochromic diarylethene derivatives, bis(2-methyl-5-phenylthiophen-3-yl)perfluorocyclopentene, was investigated by means of picosecond and femtosecond laser photolysis methods. The drastic enhancement of the reaction yield was observed only by the picosecond laser exposure. The excitation intensity effect of the reaction profiles revealed that the successive multiphoton absorption process leading to higher excited states opened the efficient cycloreversion process with a reaction yield of (50 +/- 10)%, while the one-photon absorption directly pumped to a higher excited state did not lead to the efficient cycloreversion reaction. These results indicate that not the energy of the excitation but the character of the electronic state takes an important role in the enhancement of the cycloreversion reaction.     

Synthesis of α-(aminomethylene)-9-(methoxymethyl)-9H-purine-6-acetic acid derivatives

α-(Aminomethylene)-9-(methoxymethyl)-9H-purine-6-acetamide and the ethyl acetate, 3 and 8 , have been synthesized by catalytic hydrogenation of 6-cyanomethylene-9-methoxymethylpurine derivatives 2 and 7 which were obtained by the substitution of 6-chloro-9-(methoxymethyl)purine ( 1 ) with α-cyanoacetamide and ethyl cyanoacetate, respectively. Substitution of 3 and 8 with amines gave the corresponding N-substituted α-(aminomethylene)-9-(methoxymethyl)-9H-purine-6-acetamide and the ethyl acetate 4 and 10 . Reaction of 3 with piperidine gave 9-(methoxymethyl)-9H-purine-6-acetamide ( 5 ).     

CO2-Induced Spin-State Switching at Room Temperature in a Monomeric Cobalt(II) Complex with the Porous Nature

CO₂-responsive spin-state conversion between high-spin (HS) and low-spin (LS) states at room temperature was achieved in a monomeric cobalt(II) complex. A neutral cobalt(II) complex, [Co^II(COO-terpy)₂]⋅4 H₂O ( 1⋅4 H₂O ), stably formed cavities generated via π–π stacking motifs and hydrogen bond networks, resulting in the accommodation of four water molecules. Crystalline 1⋅4 H₂O transformed to solvent-free 1 without loss of porosity by heating to 420 K. Compound 1 exhibited a selective CO₂ adsorption via a gate-open type of the structural modification. Furthermore, the HS/LS transition temperature (T_1/2) was able to be tuned by the CO₂ pressure over a wide temperature range. Unlike 1 exhibits the HS state at 290 K, the CO₂-accomodated form 1⊃CO₂ (P =110 kPa) was stabilized in the LS state at 290 K, probably caused by a chemical pressure effect by CO₂ accommodation, which provides reversible spin-state conversion by introducing/evacuating CO₂ gas into/from 1 .     

Synthesis and Thermal Reaction of 1,3-Bis(alkylseleno)allenes

Reactions of Ph(2)C(3) dianion, prepared from 1,3-diphenylpropyne and n-butyllithium, with dimethyl diselenide and benzylselenocyanate yielded 1,3-bis(methylseleno)-1,3-diphenylpropadiene and 1,3-bis(benzylseleno)-1,3-diphenylpropadiene, respectively, and the reaction with a mixture of dimethyl diselenide and benzylselenocyanate gave 1-benzylseleno-3-methylseleno-1,3-diphenylpropadiene together with the symmetric products. Thermal reactions of the 1,3-bis(alkylseleno)allenes afforded (E)- and (Z)-1,3,4,6-tetraphenyl-3-hexene-1,5-diynes along with compounds derived from cyclic dimer of the allene or diselenide via radical pathway.     

Synthesis and antitumor activity of 20(S)-camptothecin derivatives: A-ring modified and 7,10-disubstituted camptothecins.

20(S)-Camptothecin derivatives having nitro, amino, chloro, bromo, hydroxyl and methoxyl groups in the A-ring were synthesized. B-Ring hydrogenated camptothecin (2a) was converted into 10-hydroxycamptothecin (6e) by treatment with lead tetraacetate in trifluoroacetic acid. 10-Substituted derivatives (6) were obtained by a photoreaction of N-oxides (9). The cytotoxicity of the A-ring modified camptothecins was evaluated against KB cells in vitro and leukemia L1210 in mice. 7-Ethyl-10-hydroxycamptothecin (6i) was identified as a potential derivative for further modification.     

Heat capacity and magnetic phase transition of two-dimensional metal-assembled complex (NEt<Subscript>4</Subscript>)[{Mn<Superscript>III</Superscript>(salen)}<Subscript>2</Subscript>Fe<Superscript>III</Superscript>(CN)<Subscript>6</Subscript>]

Summary Heat capacity measurements of the two-dimensional metal-assembled complex, (NEt₄)[{Mn^III(salen)}₂Fe^III(CN)₆] [Et=ethyl, salen= N,N’-ethylenebis(salicylideneaminato) dianion], were performed in the temperature range between 0.2 and 300 K by adiabatic calorimetry. A ferrimagnetic phase transition was observed at T_c1=7.51 K. Furthermore, another small magnetic phase transition appeared at T_c2=0.78 K. Above T_c1, a heat capacity tail arising from the short-range ordering of the spins characteristic of two-dimensional magnets was found. The magnetic enthalpy and entropy were evaluated to be ΔH=291 J mol^-1 and ΔS=27.4 J K^-1 mol^-1, respectively. The experimental magnetic entropy agrees roughly with ΔS=Rln(5·5·2) (=32.5 J K^-1 mol^-1; R being the gas constant), which is expected for the metal complex with two Mn(III) ions in high-spin state (spin quantum number S=2) and one Fe(III) ion in low-spin state (S=1/2). The heat capacity tail above T_c1 became small by grinding and pressing the crystal. This mechanochemical effect would be attributed to the increase of lattice defects and imperfections in the crystal lattice, leading not only to formation of the crystal with a different magnetic phase transition temperature but also to decrease of the magnetic heat capacity and thus the magnetic enthalpy and entropy.     

Mechanical properties of oriented polyvinylchloride composites filled with ultrafine particles

The tensile stress-strain behaviour of undrawn and drawn polyvinylchloride (PVC) composites filled with ultrafine SiO₂ and micron sized glass particles were discussed as functions of filler content and size. For the undrawn PVC composites filled with ultrafine SiO₂ particles, Young's moduli, yield and breaking stresses increased with filler content and decreasing filler size. Whereas for the composites filled with micron sized glass particles, their Young's moduli slightly increased with filler content but both the yield and breaking stresses decreased. Oriented PVC composites were made by uniaxially drawing to × 2.5 at 100 °C. Anisotropic mechanical properties of oriented specimens were discussed in terms of compliance tensor and yield stress measured in the direction of 0°, 45° and 90° to the original stretching direction at room temperature. In the case of 70A SiO₂, all the compliance decreased with filler content, whereas those of 65μ glass, this relation was reversed. The yield stress of the oriented PVC composites showed filler size dependence similar to Young's moduli. The anisotropic yield stress of oriented PVC composites were reasonably analysed by Hill's yield criterion.     

Mn2(saltmen)2Ni(pao)2(L)2](A)2 with L=pyridine, 4-picoline, 4-tert-butylpyridine, N-methylimidazole and A=ClO4-, BF4-, PF6-, ReO4-: a family of single-chain magnets

A series of single-chain magnets, [Mn2(saltmen)2Ni(pao)2(L)2](A)2 (saltmen(2-)=N,N'-(1,1,2,2-tetramethylethylene) bis(salicylideneiminate), pao-=pyridine-2-aldoximate; A-=ClO4- with L=4-picoline; 2, 4-tert-butylpyridine; 3, N-methylimidazole; 4, and L=pyridine with A-=BF4-; 5, PF6-; 6, ReO4-; 7), was prepared by reactions between MnIII dimer units, i.e., [Mn2(saltmen)2(H2O)2](A)2 (A-=ClO4-, BF4-, PF6-) or Mn2(saltmen)2(ReO4)2, and NiII monomeric units, i.e., Ni(pao)2(L)2, in methanol/water media. The crystal structures of 4, 6, and 7 were established by single-crystal X-ray crystallography. These three compounds are isostructural with [Mn2(saltmen)2Ni(pao)2(py)2](ClO4)2 (1) (Clérac, R.; Miyasaka, H.; Yamashita, M.; Coulon, C. J. Am. Chem. Soc. 2002, 124, 12837) and crystallize in monoclinic space group C2/c. The linear arrangement of MnIII dimer units and NiII building blocks leads to an alternating chain having a repeating unit, [-(O)2-Mn-ON-Ni-NO-Mn-]. The chains are well separated with the nearest interchain intermetallic distance of 10.36 A for 4, 10.51 A for 6, and 10.30 A for 7, and there is no significant pi-pi interchain interaction between ligands. The void space between the chains is occupied by counteranions, which control the three-dimensional organization of the chains. The X-ray diffraction analysis (XRD) on a powder sample was also performed for all compounds. The XRD patterns for 1, 2, and 4-7 are very similar, emphasizing the isostructural nature of these materials although they have individually slight different interchain distances. Inversely, the XRD pattern for 3 reveals a completely different shape being indicative of the peculiar crystal packing compared to the others. Nevertheless, the one-dimensional nature of the structure is also kept in 3 as indicated by magnetic measurements. The whole family of compounds exhibits quasi-identical magnetic behavior compared to that described for 1. Above 30 K, the heterometallic chain can be described as an assembly of antiferromagnetically coupled Mn...Ni....Mn trimers (via oximate bridge, -24.2 K相似文献