Doisynolic acid

Many years ago, doisynolic acid (39), a steroid degradation product, was shown to have such activity. Over the years many simple compounds have been synthesized following the idea of molecular dissection. One of these is fenesti-el (38). Hageman s ester (35) is alkylated to 36 by t-BuOK and ethyl-bromide. The regioselectivity observed is generally... 

Dobutamine, 53 Doisynolic acid, 9 Domazoline, 256 DOPA, 52, 119 Dopamantine, 52 Dopamine, 51 Dorastine, 457 Doxapram, 236, 237 Doxaprost, 3 Drocinonide, 186... 

Although known for almost forty years, and in spite of a total synthesis of its racemate, the stereochemistry of doisynolic acid has remained in doubt. This problem has now been settled by a stepwise chemical conversion (Scheme 23) of 14)5-oestrone methyl ether (339), prepared from natural oestrone (114a), into c/s-doisynolic acid methyl ether (342). Osmium tetroxide oxidation of the enol acetate corresponding to (339) provided 16a-hydroxy-14)S-oestrone methyl ether. Subsequent periodic acid oxidation afforded the lactol (340), which upon treatment with diazomethane gave the aldehydo-ester (341). Electrochemical reduction of the aldehyde (341) afforded a methyl ester which by alkaline hydrolysis provided (-f )-ds-doisynolic acid 3-methyl ether (342), thus defining its complete stereochemistry. ... 

Doisynolic Acid. I-Ethyl-1,2,3,4,4a,9,I0,I0a-octa-hydro-7-hydroxy-2-methyl-2-phenanthrenecarboxylic acid ] -ethyl -7-hydroxy-2-methy]-],2,3,4,4a,9,]0,]0a-octahy-dr-ophenanthrene-2-carboxylic add 3-hydroxy-16,17-seco-estra-l,3,5(10)-trien-17-oic acid. mol wt 288.37. 

In the last case, a mixture of isomers of doisynolic acid (118) was also obtained, but it was impossible to obtain individual products from it. 

From the keto esters A, B, and C (119, 124, 123) were also obtained five spatial isomers of doisynolic acid [233, 235] by the method described previously (Schemes 3 and 11) for the synthesis of bis - and monodehydro-doisynolic acids. The structures assigned to them apparently require additional confirmation, since they are not fully in agreement with the formulas of the initial keto esters given in Scheme 12. 

Syntheses via Diphenylethane Derivatives. Total syntheses of doisynolic acids, their 8-aza analogs, and numerous tricyclic ABC intermediates have been effected by this route (Schemes 48-51). 

---