Digitoxigenins

The most difflcult pharmaceutically relevant oxidation of steroids is the introduction of a 14 -hydroxyl group. This functional group is found in heart-active steroids (cardenolides) such as digitoxigenin, which also contain a 17/J-butenolide substituent. The 14/ -hydroxyl group is easily cleaved off by dehydration and must therefore not be treated with Lewis or... 

It is known that the presence of the 143-hydroxyl group and a sugar at the 3 position are absolute requirements for activity. A modified drug actodigin (100) demonstrates that reversal of the lactone 17 is consistent with activity. Reduction of digitoxigenin 91, the aglycone of digitoxin... 

Preliminary experiments on the coupling of the chloride (lb) with digitoxigenin (3/ ,14,/ -dihydroxy-5/ -card-20(22)-enolide) in the presence of silver carbonate, led to gross decomposition of the halide, and it was suspected that, under the conditions of the experiments, the silver carbonate was causing elimination of hydrogen chloride. When, however, digitoxigenin was treated with an excess of lb in a small volume of... 

Digitoxigenin is a heart stimulant obtained from the purple foxglove Digitalis purpurea and used in the treatment of heart disease. Draw the three-dimensional conformation of digitoxigenin, and identify the two —OH groups as axial or equatorial. 

What product would you obtain by reduction of digitoxigenin (Problem 27.39) with LiAl.H4 By oxidation with pyridinium chlorochromate ... 

Digitoxigenin, structure of, 1097 Digitoxin, structure of, 989 Dihalide, alkynes from, 261 Dihedral angle, 94 Diiodomelhane. Simmons-Smith reaction with, 228-229 Diisobutylaluminum hydride, reaction with esters, 812 structure of, 699 Diisopropylamine, pK.d of, 923 1,3-Diketone, pfCa of, 852 Dimethyl disulfide, bond angles in, 20 structure of, 20 Dimethyl ether, electrostatic... 

P2j Z = 2 D, = 1.24 R = 0.05 for 2,421 intensities. This molecule is a cardenolide / -D-glucopyranoside. The pyranoside conformation is 4C4, with Q = 58 pm, 0 = 6°. The terminal lactone ring is planar. The conformation was compared with that of digitoxigenin by means of molecular-mechanics calculations. 

An analogous dehydration in the synthesis of lactone substituted derivatives of digitoxigenin is reported in reference [21a]. 

Alkyl ethers of ttigitoxigenin. The Williamson ether synthesis fails when applied to digitoxigenin (1). In fact, only three successful methods arc known for preparation of the 3 alkyl ethers. The 3-melhyl ether can he obtained in 66, yield... 

Cardenolides.1 Digitoxigenin (7) has been synthesized by reaction of a 3/J-benzyloxy a./3-unsaturated 17-ketone (2) with 1, followed by further transformations as shown. Allylic rearrangement of the initial product 3 results in 4. After reduction... 

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