Suppression Of Ages Formation In Spontaneous Diabetic OLETF Rat By Organic Germanium Compound [Poly-trans-(2-carboxyethyl) Germasesquioxane] (Ge-132)

The model rat for the type 2 diabetes mellitus (NIDDM) in human were observed for 72 weeks after birth, administering an organic germanium compound [Bis(2-Carboxyethyl) germasesquioxane, Ge-132] perorally 100 mg/kg/day since 24 weeks old. Clinical examinations were followed throughout the observation period. Blood and urinary glucose in positive control OLETF rats tended to be higher than those treated with Ge-132. At the end of the 72nd week, animals were sacriificed to examine the pathological changes, specifically in pancreas, kidney and brain. Anti-AGE antibody stained proximal and distal tubles and basement membrane of glomerules in kidney, and accumulated AGE masses in cortex, hippocampus and cerebellum of OLETF rat's brain. Amyloid stains by basic congo red on kidney and brain revealed that the deposits of amyloid in kidney mesangium and in cortex, hippocampus and cerebellum were observable in OLETF rats. Ge-132 suppressed the deposition of amyloid tangles in kidneys and brains. Anti rat complement C'3 antibody reacted with AGE and amyloid tangles that were sensitive to anti-AGE antibody. AGE generated in vitro by incubating human serum, human gammaglobulin (HGG), or bovine serum albumin (BSA) with glucose activated complements, showing the consumption of complements in the hemolysis of hemolysin-coated sheep red blood cells. A novel device Quantum Resonance Spectrometer (QRS) could read the subtle bio-magnetism memorized in serum samples, demonstrating quantitative values reflecting the patho-physiology of OLETF rats.     

Conformational features and chemical behavior of 5H, 7H-dibenzo[B,g][1,5] dithiocin oxides: 1,5-Oxygen shift via a dithiodication intermediate

Some 5H,7H-dibenzo[b,g][1,5]dithiocin oxides ( 4–8 ) and their related compounds 9–13 were prepared and the assignment of the most favorable conformation was carried out on the basis of the characteristic ¹H NMR spectral data. Only a single conformer (BC: boatchair form) exists for 4 , 5 , and 8–13 , while two conformers (BC and TB: twist-boat form) are apparent for 6 and 7 . Oxidation and methylation of 4 gave exclusively a single geometrical isomer ( 8 and 13 , respectively). These results are interpreted as a sterically preferential attack of electrophiles on the BC conformer of the starting material. A 1,5-oxygen shift of 4 occurred smoothly to give 6 in the presence of trifluoroacetic acid in CDCl₃ solution. The mechanistic investigation is described briefly. Differences in chemical behavior between dibenzodithiocin 12-oxide 4 and dibenzothiazocine 12-oxide 2 are also discussed on the basis of the conformational features.     

Novel results obtained by freezing berry pseudorotation of phosphoranes (10‐P‐5)

By freezing Berry pseudorotation of spirophosphoranes with recourse to the rigidity of the Martin bidentate ligand, we successfully prepared configurationally stable enantiomeric pairs of optically active phosphoranes, and could isolate “anti‐apicophilic” C‐apical O‐equatorial (O‐cis) phosphoranes. The effect of σ*_{P O} orbital of the O‐cis phosphorane was investigated both experimentally and theoretically. O‐cis phosphoranes were revealed to be much more electrophilic at the phosphorus atom than O‐trans isomers by experimental studies. The acidity of the α‐proton of an O‐cis benzylphosphorane was found to be higher than that of the corresponding O‐trans isomer. By the reaction of the α‐carbanion of an O‐cis benzylphosphorane with PhCHO, we succeeded in the first isolation and full structural characterization of a 12‐P‐6 phosphate bearing an oxaphosphetane ring, the intermediate in the Wittig type reaction using a 10‐P‐5 phosphorane. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:390–396, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10072