Eugene Paul Oliveto

Total synthesis of optically active (−)17β-hydroxy-Δ9(10)-desA-androsten-5-one

Abstract (±)7,7a-Dihydro-1β-hydroxy-7aβ-methyl-5(6H)-indanone was resolved via the hydrogen phthalate-brucine salt. The dextrorotatory enantiomer (+)4 was then converted in a 5-step stereospecific total synthesis to the important BCD tricyclic intermediate (−)13. The synthesis also adds additional proof for the absolute configuration of the bicyclic keto alcohol (+)4 by correlation with (±_13, a known degradation product of natural steroids.

A history of significant steroid discoveries and developments originating at the Schering Corporation (USA) since 1948.

A firsthand historical account of some of the significant contributions of the steroid research group at the Schering Corporation (Bloomfield, NJ, USA) to the discovery and/or development of important therapeutic agents is presented. These include the discovery of the antiinflammatory corticosteroid drugs prednisone, prednisolone, and betamethasone, all of which, more than 30 years after their introduction, continue to enjoy wide use in human and animal medical practice throughout the world.

Structural determination of ascorbic acid 2-o-phosphate formed via acid hydrolysis of an ascorbic acid 3-O-phosphinate

Abstract The synthesis and X-ray structural determination of 3-O-[(bis-morpholino)phosphinyl]-5,6-O-isopropylidene- l -ascorbate (9) are described. Acid-catalyzed hydrolysis of 9 afforded the 2-O-phosphate 6. Definitive structural proof of 6 is based on a study of the pH profile of its UV spectra as compared with those of ascorbic esters, 2 and 9 (Figs. 1–3).

17-Esters and 17, 21-diesters of 9α, 11β-dichlorocorticoids. Synthesis and anti-inflammatory activity

Abstract The syntheses of some 17,21-diesters of dichlorisone (9α, 11β-dichloro-17α, 21-dihydroxy-1,4-pregnadiene-3, 20-dione), 16α-methyldichlorisone and 16β-methyldichlorisone and some 17-monoesters of 16α-methyldichlorisone are reported. Anti-inflammatory activity, as measured by a granuloma pouch technique, reached a maximum for the 17-butyrate and 17-valerate of 16α-methyldichlorisone and for the 17, 21-dipropionate and 17, 21-dibutyrate of 16α-methyldichlorisone.

The synthesis of 25-hydroxy-cholecalciferol-23,23,24,24-t4 of high specific activity

Abstract Catalytic tritium reduction of cholest-5-en-23-yne-3β,25-diol diacetate ( VIII ) gave cholest-5-ene-3β,25-diol diacetate- 23 , 23 , 24 , 24 - t 4 ( IX ) having a specific activity of 92 Ci/mmol. Bromination, dehydrobromination and hydrolysis of the labelled material gave cholesta-5,7-diene-3β,25-diol- 23 , 23 , 24 , 24 - t 4 ( XI ) which was photolyzed to the previtamin and then thermally equilibrated to 25-hydroxy-cholecalciferol- 23 , 23 , 24 , 24 - t 4 ( I ).

Vanadium (IV) chloride induced allylic rearrangement of a steroidal alcohol

Abstract 17-α-Vinylestradiol 3-methyl ether 1 undergoes allylic rearrangement in the presence of vanadium (IV) chloride to produce a Δ17(20)-21-chloride 2 in high yield. The latter compound can be converted to the 21-acetoxy-17α-hydroxy-20-keto side-chain by two different routes.

Ketone exchange in a sugar bisacetal

Abstract An acid-catalyzed reaction of 2,3:4,6-di- O -isopropylidene-α- l -sorbofuranose with ketones resulted in replacement of the isopropylidene groups with alkylidene groups derived from the ketonic solvent. Kinetically controlled exchange occurs at the 4,6-position. Under equilibrium conditions exchange occurs at the 2,3- as well as the 4,6-position. Participation by the hydroxyl group at C-1 in the rate determining step of exchange at the 2,3-position could not be demonstrated.