No abstract

To a solution of 8.2 g (0.046 mol) of III-24, 2.8 g of dry CjHsN, and 80 ml of dry PhMe, at -10°, was added dropwise 47 ml of a 15% w/v of COCli in PhMe. The work-up of this reaction mixture and the subsequent reaction of the intermediate carbamoyl chloride with EtOH-NIL followed the published procedure.Zc The yield of crude III-27 was 1.45 g; chromatography, in CeHe solution, on 60 g of alumina (Harshaw, Chromatographic Grade), followed by successive elutions with C«H6 and (-PrOH, and repeated recrystallizations from ß 6 were required to give pure III-28.8 5-Acetyl-7-chloro-5,ll-dihydrodibenz[b,e] [l,4]oxazepine (III-10).-A solution of 2.0 g (0.0087 mole) of 7-chloro-5,1 l-dihydro-' urm, < l at. dibenz]f),<:j [ 1,4] oxazepine,2* 25 ml of Ae-O, and 0.4 g of p-toluenesulfonic acid was heated under reflux for 2 hr, coned to dryness, and the residue distributed between 50 ml of Et»<) and 25 ml of said aq NaHCO». The Et»0 layer was sepd, washed with said a<[ NaCl, dried, and coned to give 2.4 g of 111-1(1.6-[ (o-Bromobenzy 1 )oxy] -Qf,a,a-trifluoro-»i-acetotoluidide . A mixture of 20.0 g (0.052 mol) of II-2. 8.6 g (0.1 1 mol) of anhyd AcONa, and 120 ml of glacial AeOH was heated under reflux for 3 hr, cooled somewhat, and poured into 300 ml of HiO. The oil, that sepd initially, solidified, and was filtered and dried to give 10.4 g of II-4.(8) The difficulties encountered in this synthesis are similar to those previously described in the oxazepine series, and are involved in the reaction of tiie heterocycle with phosgene."c Synthesis and Hypocholesterolemic Activity of Alkylidenedithio Bisphenols .

No abstract

The search for new hypocholesterolemic agents has resulted in the discovery of many active compounds in the last few years. I t is highly probable that the majority of these affect cholesterol biosynthesis in some way. In particular, several have been reported which inhibit one of the later reactions in the sequence (1-3).The purpose of the present paper is to report the investigation of a member of a series of new hypocholesterolemic agents having ferrocene as a component of their structure. The results of this study show that this compound, N -( ferrocenylmethyl) piperidine, causes abnormal quantities of a compound resembling 7-dehydrocholesterol to acumulate in serum and liver, and probably acts by inhibiting 7-dehydrocholesterol reductase. Very little work has been reported on the pharmacological activity of ferrocene compounds, although it has been suggested that ferrocene or ferrocene derivatives could be used as hematinic agents (4, 5).Experimental Methods. Animal studies. The chemical was adsorbed on silica gel from an acetone solution and mixed with ground rodent mash on a roller mill to give a concentration of 0.007%. Groups of six male weanling rats (Harlan Wistar strain, Harlan Industries, Cumberland, In.) were maintained on the experimental diet for 1 week, then killed and blood and liver samples were collected.Andytical. A modification ( 6 ) of the method of Sperry and Webb (7) was used for the determination of "fast-acting" sterols and cholesterol. This method takes advantage of the fact that the so-called "fast-acting" sterols give full color development in 12 min at O", whereas cholesterol does not react at all in this time. After standing at 25" for an additional 30 min, the absorbancy is again determined. After a suitable correction for the contribution of " fast-acting" sterols to the latter reading, the amount of cholesterol can be determined. Materials absorbing at 28 1.5 mp were determined spectrophotometrically by measuring the absorbancy in ethanol of nonsaponifiable material from serum and liver. Correction for extraneous absorption was made using a three-point procedure (8) with selected wavelengths of 276.5, 281.5, and 284.5 mp. The reference material for "fast-acting" sterols and the 281.5 mp determination was 7-dehydrocholesterol.A spectrophotometric assay (9) was used to determine inhibition of the enzymatic reduction of 7-dehydrocholesterol in vitro.Each flask contained 13,OOOg rat liver supernate equivalent to 0.25 g of liver, 0.75 pmoles of 7-dehydrocholesterol, 1.7 pmoles of NADP, 30 pmoles of nicotinamide, 15 pmoles of glucose-6-phosphate, and 70 pmoles of Tris-maleate buffer, pH 7.2. The total volume was 1.0 ml and the incubations were carried out in duplicate at 37" for 2 hr under nitrogen.

Die Mercaptophenole (I) wurden nach literaturbekannten Methoden dargestellt und mit verschiedenen Ketonen (II) in Methanol in Gegenwart von "etwas Chlorwasserstoff bei 50°C kondensiert zu den Bisphenolen (III).