On Cardioactive Steroids. XVI. Stereoselective β-Glycosylation of Digitoxose: The Synthesis of Digitoxin

Two methods for stereoselective β-glycosylation of digitoxose were developed. The first achieved stereocontrol by a 1,3-participation of a N-methylurethane group under acid catalysis. The second utilized mercuric-ion catalyzed cleavage of thioglycosides and a 1,3-participation of a p-methoxybenzoyl group in a neutral medium. The first highly stereoselective and quite efficient synthesis of digitoxin ( C7 ) was achieved by a combination of these methods. The furyl-substituted precursor IV of digitoxigenin (Scheme 1) was used as aglycone, and the furan group was converted to the unsaturated lactone of digitoxin by our known oxidation procedure (m-chloroperbenzoic acid/NaBH₄) after the assembly of the carbohydrate portion of the molecule and its deblocking was completed.     

Synthesis of Cardioactive Steroids III Modified Synthetic Route to Isocardenolide

A modified synthetic route to isocardenolide (I) via furan intermediate (6) was studied. The diene (4) could easily be synthesized from carbinol (1) or acetate (2). Dissolving metal reduction of diene (4) to Δ¹, 17β-furyl compound (6) was successfully achieved.     

Synthesis of a Fluorescent,Cardioactive Analogue Digoxin

Abstract

In order to develop a better understanding of the mechanism of action of the cardioactive steroid glycoside digoxin, we have synthesized a fluorescent analogue of this drug which retains biological activity. Fluoroscein isothiocyanate has been coupled to digoxin via an ethyl lysine bridge, after mild periodate oxidation of the terminal glycase moiety. The conjugate can displace oubain from the plasma membrane digoxin receptor, Na⁺/K⁺ ATPase and can itself be displaced by native digoxin. The structure of the conjugate based on FAB mass spectroscopy is presented.     

Synthesis and Properties of Nonatungstotricobaltosilicate Isomers

Introduction Recently substituted-type of heteropolyanions has received much attention from the point of view of their catalysis. Hill, Finke, Neumann reported respectively that transition metal mono-substituted heteropolyanions PW_(11) M, P_2W_(17)M and SiW_(11) Ru have an ability to catalyze the epoxidation of olefin. We discovered that trisubstituted Keggin heteropolyanions have this property too. This paper describes the synthesis, properties of α- and β-[SiW_9O_(27)Co_3(H_2O)_3]~(10-) and its catalysis for the epoxidation of olefin by PhIO.     

Steroids. Synthesis of 1,4-oxazine derivatives of estrone

Estratrieno[3,2-b]-1,4-oxazin-3′-one (V) and estratrieno[3,4-b]-1,4-oxazin-3′-one (VI) have been converted to the corresponding amidines. The tautomerism of the thiones and the amidines are discussed.     

Optimization of Synthesis of Mono-O-methylglycerol Isomers

Parameters were refined for synthesis of glycerol 1-monomethyl ether by methylation of glycerol with dimethyl sulfate in the presence of alkali; a gas-liquid chromatographic procedure was proposed for identification of structural isomers of mono-O-methylglycerol.     

Synthesis and Hemolytic Propertiesof Arvensoside B Isomers

Summary.  The first partial syntheses of galactosyl-glucosyl oleanolic acid disaccharides are described. Arvensoside B and calenduloside A, which have earlier been isolated from Calendula arvensis and Calendula officinalis, and some further oleanolic acid glycosides were prepared from differently linked acetobromo sugars. The hemolytic properties of these saponins were investigated. Systematic variation of the carbohydrate structure and comparison with already synthesized glucosyl-glucosyl analogues enable general conclusions about structure-activity relationships. Received April 17, 2000. Accepted May 3, 2000     

Stereoselective Synthesis of 22,24-Dihydroxy Steroids

anti-22,24-Dihydroxy steroid derivatives were synthesized by successive transformation of 22-hydroxy-24-oxo steroids into -silyloxy ketones and intramolecular reduction of the latter.     

The Tricyclooctanone Approach to the Total Synthesis of Steroids. The Cyclization of the A-CD Unit

The first steps of a novel approach to the total synthesis of 9, 11-dehydroestrone via tricyclo[3.3.0.0^2,8]octan-3-one (2) are described. One route involves a tandem-type transformation of the key intermediate 3 (A-CD unit) consisting of cyclopropane cleavage and ring B closure to afford C, 18-bisnor-13 α, 17 α-estradiol derivatives. E.g. the 3-methoxy-9 ζ-hydroxy-17 α-methanesulfonyloxy derivative (-)- 6 has been synthesized in 8 steps and 10% overall yield from 1,3-cyclohexadiene. As an alternative, the A-CD type intermediate 4b has been prepared and could be used for a ring C enlargement prior to cyclization.     

Total Synthesis of Indole and Dihydroindole Alkaloids. XVIII. Isomers and analogues of vinblastine

The synthesis and conformational analysis of (3′R)-3-hydroxyleurosidine ( 5 ), (3′S)-3-hydroxyleurosidine ( 10 ), (3′S)-3-acetoxy-4′-deoxyleurosidine ( 15 ), (3′R)-3-acetoxy-4′-deoxyleurosidine ( 23 ), (3′R)-3-acetoxy-4′-deoxyvinblastine ( 16 ), (3′S)-3-acetoxy-4′-deoxyleurosidine ( 28 ) is discussed.