Strophanthidin, synthesis

The full account has appeared " of the synthesis of the A °-marine steroid (284). In addition the isolation and synthesis of the related 3iS-hydroxy-A -compound (285) " and the lla-hydroxy-3-oxo-A -compound (286) were reported. In the synthesis of (286) the 17/3-ethenyl group was constructed through exhaustive methylation of the 20-amino-compound followed by Hofmann elimination. Epimerization of pregnenolone at C-17 led to the synthesis of a number of 20-methyl-17a-pregnanes. Syntheses have been reported for the four isomeric 3,ll-diamino-5a-pregnanes, and the 6,19-dimethoxy-3,5-cyclopregnan-20-one (287) was synthesized in model experiments aimed at a strophanthidin synthesis. ... 

ZnCl2 is essential. The reaction was utilized in the synthesis of strophanthidin. Only the q, /3-alkene in the a, fi- and 7, (5-unsaturated ketone 51 is reduced selectively[47], Triethoxysilane is another reducing agent of the enone 52 and simple alkenes[48]. 

In their synthesis of convallatoxin, Reichstein and coworkers16 made some minor modifications in the Meystre-Miescher procedure. Because of the low solubility of strophanthidin (2) in benzene, the anhydrous aglycon was dissolved in a small volume of absolute p-dioxitne. Pure, dry silver carbonate was introduced and, under efficient stirring, a solution of the halide in benzene was added over a period of three hours, while distillation was maintained at a rate equal to that of the addition, thus keeping the volume of the solution in the flask at a constant (and small) volume. After addition of the halide was complete, a small volume of absolute benzene was added dropwise over a period of one hour, with distillation maintained as in the foregoing. By this procedure, the yield of tri-O-acetylcopvalla-toxin amounted to 44%. 

Following this work, Reichstein and coworkers15 effected the first partial synthesis of a naturally occurring cardenolide, convallatoxin. Convalla-toxin [3/3-0-(6-deoxy-a-n-mannopyranosyl) strophanthidin (9)] is considered to be the most potent of all the known, naturally occurring cardenolides, and is obtained from the blossoms of the lily-of-the-valley (Convallaria majalis). The coupling of strophanthidin (2) with 2,3,4-tri-0- acetyl-6-deoxy-a- L-mannosyl bromide was performed using silver car-... 

Neighbouring group participation has been employed to control the regioselectivity of HOBr addition across a double bond in the crucial step of the synthesis of strophanthidin. Two molecules of the reagent were used in order to introduce two hydroxy groups in one step (148 - 149)241. 

Selective oxidation of a primary alcohol. The final step in a recent synthesis of strophanthidin required selective oxidation of the primary hydroxyl group of stro-phanthidol (1) to an aldehyde group. Oxidations with chromic acid, N-haloamides,... 

Further studies in the synthesis of 14-deoxy-14a-strophanthidin were reported.220 221 A new synthesis of 15-hydroxy-cardenolides involved the addition of 2-methoxy-4-furyl lithium to A15-17-oxo-compounds as a key step.222 A novel approach to cardenolides from 17-oxo-steroids is outlined223 in Scheme 13. Anhydroxysmalo-... 

Interest in the possible cytotoxic activity of the amino-glyco-cardenolides has led to the synthesis of 3/S-(4 -amino-4, 6 -dideoxy-) -D-galactopyranosyl)-14j5-hydroxy-5) -card-20(22)-enolide (33) and the 2-amino-2-deoxy- -D-gluco-pyranosides of digitoxigenin, of strophanthidine (34), and of pregnenolone. ... 

Addition and elimination of 5-unsubstituted fiaran-2-ones has been shown with primary amines. In 1960, while developing a synthesis of amino derivatives of strophanthidin, Bembry and coworkers speculated that 4-phenylfuran-... 

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