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Acidic treatment of swinholide A (1), which was characterized as the major cytotoxic macrolide from the Okinawan marine sponge Theonella swinhoei, provided several isomeric macrolides having different size of the dilactone ring structure. From the structure-activity correlation viewpoint, the in vitro cytotoxicities and in vivo antitumor activities of these dimeric macrolides, together with two monomeric macrolides which were synthesized from 1, have been examined.

To determine favorable conditions for preparation of syndiotactic polymers, various factors which influence the stereoregulation of vinyl esters were studied. In bulk polymerizations, vinyl esters having bulky substituents or polar substituents were found most suitable for the syndiotactic polymerization. Tri‐n‐butylborane and azobisisobutylonitrile showed some difference in stereoregulation, the magnitude of the difference being dependent on the type of vinyl ester used. Solvents were found to have a significant effect on stereoregulation. Some gave higher syndiotacticity than bulk and some gave lower syndiotacticity.

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Kneading of powder materials [1][2][3] has been well used in the pharmaceutical, agriculture, food, chemical, forage and fertilizer industries. Most of the cases, kneading operation is conducted just before the extrusion or molding processes, and the performance of kneading seriously affects quality of the final product or process efficiency. Therefore, it is important to quantitatively analyze and monitor the kneading process.So far, a high shear mixer has been well used for wet granulation 4) as well as for wet kneading. In the case that the high shear mixer is used for wet kneading, several advantageous points such as easy to disassemble with easy cleaning can be pointed out. However, the problems such as enormous sticking on the vessel wall or larger physical strength of extruded pellets that may cause longer dissolution time have also been known on the contrary. It is required to improve the problems of high shear mixer while keeping the advantageous points when applied to wet kneading.In this study, a multi-functional vertical high shear kneader has been newly developed and applied for wet kneading. Wet kneading of pharmaceutical powders composed of acetaminophen and excipients was conducted under various blade components and operating conditions. Dispersion of aqueous binder and compression properties of wet mass was investigated to quantitatively analyze the kneading condition. Dried pellets were then produced through a dome type extrusion granulator and a fluidized bed drier, and physical properties of the pellets were examined experimentally.Comparison between kneading performance of the novel kneader and of a conventional high shear mixer (granulator) was also conducted. ExperimentalApparatus Figure 1 shows a schematic diagram of multi-functional vertical high shear kneader (SPG-10, Fuji Paudal Co., Ltd.) developed. The vessel is a laboratory size, which has an inner diameter of 290 mm and a capacity of 10 l. The bottom of the vessel is equipped with a kneading blade that rotates horizontally. Several operating parameters such as torque of main shaft, power consumption of motor drive and temperature of kneaded mass can be continuously measured and monitored via a personal computer. Chopper blade can also be installed onto the sidewall of the vessel, if necessary. Figure 2 illustrates a newly developed kneading blade, and Fig. 3 shows appearance of various blades used. The kneading blade is composed of four parts; (a) scraper, (b) main blade, (c) dispersion blade, and (d) cap. The main blade has an edge having inclination of 20 degrees to the backward, opposite direction of the blade movement. This is designed so as to press down the wet kneaded mass, and to add high compaction force and high shear stress to the mass (typically, main agitator blade of high shear mixer (granulator) has an edge to the opposite direction of our kneading blade, thus powders are lifted up by the edge inclination). The dispersion blade equipped on the top of the main blade works to move away the wet mass to the vessel outsid...

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The synthesis of cubebol and the related compounds from (−)-carvone is described. In the preparation of the key intermediate, 7,10-trans-2,6-epi-2-acetoxy-7-isopropyl-10-methyltricyclo[4.4.0.01,5]decan-4-one (10) the electrochemical acetoxylation reaction could be used as an effective method for introducing the acetoxy group at C-2 carbon atom instead of the carboxy function of 7,10-trans-2,6-epi-4-oxo-7-isopropenyl-10-methyltricyclo-[4.4.0.01,5]decan-2-carboxylic acid (6a). The condensation of (+)-p-menth-8-en-2-one (2a) prepared from (−)-carvone with dimethyl succinate afforded Stobbe half-ester 3, which provided the diazoketone 4 smoothly. Thermal decomposition of 4 in benzene gave intramolecular adducts 5a and 5b (4 : 1). Hydrolysis of 5a afforded 6a in ca. 40% yield. Electrolysis of 6a in AcOH-t-BuOH-Et3N (2 : 1 : 0.1) using platinum electrodes gave 10 in 72% yield. Elimination of acetic acid gave two isomers 11a and 11b (3 : 1) in 87% yield and subsequent methylation of 11a afforded 7-isopropyl-4,10-dimethyltricyclo[4.4.0.01,5]deca-2-en-4-ol (12) in 82% yield, which on hydrogenation gave the desired product 1a (36.5%) along with the epimer 1b (36.5%).