Effect of compression on interaction between 1,4-dihydropyridine compounds and lactose monohydrate

Manidipine dihydrochloride or benidipine hydrochloride will change to hydrate form in part, when differential scanning calorimetric (DSC) measurement is carried out together with lactose monohydrate. This interaction was accelerated by compressing their mixture. It can be suggested that the interaction may cause by the disruption of crystal structure of lactose monohydrate due to compression to set free of water molecules. A new DSC peak at 170 degrees C, which was not observed in each component, appeared in DSC measurement of a mixture. This will be based on hydrate formed by the interaction, i.e., movement of water molecules. The profile of the plotting of the DSC peak area ratio before and after compression against the compression force changed by the molar ratio of lactose monohydrate in a mixture. In the case of low molar ratio of lactose monohydrate, profiles for manidipine dihydrochloride and benidipine hydrochloride differed from each other. This will be because manidipine dihydrochloride is stickier than benidipine hydrochloride. The profile for manidipine dihydrochloride became more gradual and showed lag compression force region when the amount of addition of the lubricant, magnesium stearate in a mixture increased. The endothermic peak area at 170 degrees C for manidipine dihydrochloride was larger than that for benidipine hydrochloride. It should be suggested that benidipine hydrochloride is easier to be transformed to its hydrate than manidipine dihydrochloride.     

Non-linear structures in the non-critical NSR string

We investigate the Ward identities of theW symmetry in the super-Liouville theory coupled to the super-conformal matter of central charge . The theory is classified into two chiralities. For the positive chirality, all gravitationally dressed scaling operators are generated from theq–1 gravitational primaries by one of the ring generators in the R-sector acting on them repeatedly. After fixing the normalizations of the dressed scaling operators, we find that the Ward identities are expressed in the form of theusual W _q algebra constraints as in the bosonic case:W _n ^(k+1) ,=0, (k=1,...,q–1;nZ1–k), where the equations for even and oddn come from the currents in the NS- and the R-sector respectively. The non-linear terms come from the anomalous contributions at the boundaries of moduli space. The negative chirality is defined by interchanging the roles ofp andq. Then we get theW _p algebra constraints.     

Direct catalytic asymmetric Michael reaction of hydroxyketones: asymmetric Zn catalysis with a Et2Zn/linked-BINOL complex

Full details of our direct Michael addition of unmodified ketones using new asymmetric zinc catalysis are described. Et(2)Zn/(S,S)-linked-BINOL complexes were successfully applied to direct 1,4-addition reactions of hydroxyketones. The first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was effective for 1,4-addition of 2-hydroxy-2'-methoxyacetophenone (3). Using 1 mol % of (S,S)-linked-BINOL 1 and 2 mol % of Et(2)Zn, we found that a 1,4-addition reaction of beta-unsubstituted enone proceeded smoothly at 4 degrees C to afford products in high yield (up to 90%) and enantiomeric excess (up to 95%). In the case of beta-substituted enones, however, the first generation Et(2)Zn/(S,S)-linked-BINOL 1 = 2/1 system was not at all effective. The second generation Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 with MS 3A system was developed and was effective for various beta-substituted enones to afford products in good dr, yield (up to 99%), and high enantiomeric excess (up to 99% ee). With the Et(2)Zn/1 = 4/1 systems, catalyst loading for beta-unsubstituted enone was reduced to as little as 0.01 mol % (substrate/chiral ligand = 10 000). The new system was also effective for 1,4-addition reactions of 2-hydroxy-2'-methoxypropiophenone (9) to afford chiral tert-alcohol in high enantiomeric excess (up to 96% ee). Mechanistic investigations as well as transformations of the Michael adducts into synthetically versatile intermediates are also described.     

Enantio- and diastereoselective, stereospecific mannich-type reactions in water

Catalytic asymmetric Mannich-type reactions in water proceeded in high yields and selectivities using a combination of ZnF2 and a chiral diamine that has the methoxy groups on the aromatic rings. In these reactions, either syn- or anti-Mannich adducts were stereospecifically obtained from (E)- or (Z)-silicon enolate, in contrast with most asymmetric Mannich-type reactions.     

Synthesis and Crystal Structure of p-tert-Butylthiacalix[8]arene: A New Member of Thiacalixarenes

Even though it was obtained in poor yield, p-tert-butylthiacalix[8]arene (TC8A) has been synthesized as a new member of thiacalix[n]arenes by the terephthalate-induced cyclization of a mixture of acyclic oligomers, which was obtained by the reaction between p-tert-butylphenol and sulfur with CaO in ethylene glycol/diphenyl ether system. Slow evaporation of the chloroform solution of TC8A afforded guest-free crystals consisting of TC8A itself. The close-packed crystal structure of TC8A resembles that of p-tert-butylcalix[8]arene (C8A) closely, containing a plated loop molecular structure.This revised version was published online in July 2005 with a corrected issue number.     

Cisplatin suppository: preparation, release characteristics and clinical evaluation

Cisplatin (CDDP) has attracted attention as a chemotherapeutic agent for the treatment of uterine endometrial carcinoma but causes serious side effects, including renal toxicity. CDDP suppositories containing NaCl at different concentrations were prepared to enhance the efficacy and to reduce the side effects of CDDP. The release characteristics, melting point and viscosity of the suppositories were first studied. The rate of CDDP release increased as the NaCl concentration increased: it was 12% 12 h after administration of suppositories containing no NaCl, but 32% with 0.2% NaCl. The melting point was raised by addition of NaCl: 35.5 degrees C without NaCl and 36.5 degrees C with 0.2% NaCl. Addition of 0.2% NaCl doubled the viscosity. Clinically, the suppository containing 0.06% NaCl was given to 3 patients with endometrial carcinoma twice a week for 3 weeks to examine serum CDDP levels and endometrial absorption. Patients with endometrial carcinoma showed different peak plasma platinum (Pt) levels which were as low as 0.12, 0.06 and 0.22 micrograms Pt/ml with similar patterns of change in the level. Radiographic analysis revealed many Pt particles in sections of necrosed endometria after 21d of the treatment. No side effects of CDDP were found in biochemical testing or subjective symptoms.     

New methods and reagents in organic synthesis. 56. Total syntheses of patellamides B and C,cytotoxic cyclic peptides from a tunicate 2. Their real structures have been determined by their syntheses.

The proposed structures of patellamides B and C, cytotoxic lipophilic cyclic peptides from a marine tunicate, have been revised on the basis of the spectral data of their partial hydrolysates, and their revised structures have been synthetically confirmed by the use of diphenyl phosphorazidate(DPPA) and diethyl phosphorocyanidate(DEPC).     

Diethyl phosphorocyanidated (DEPC). A novel reagent for the classical Strecker's α-amino nitrile synthesis

Diethyl phosphorocyanidate (DEPC) can be efficiently used for the synthesis of α-amino nitriles from carbonyl compounds and amines. The reaction may be called a modified Strecker synthesis.