Abstract:

Some investigations discovered that estradiol has specific affinity to the tumor sites. With estradiol as the carrier chlorambucil can accumulate specifically t o the tumor sites and exhibit a strong antitumor effect. Among the reported estr adiol carriers 1-methyl-3-hydroxy-1,3,5(10),9(11)-estratetraene-17-one (1) is characterized by high affinity to the tumor sites and low estrogenic activity, and thus exhibits promising use. In the present pa per nitormethylation and nitroethylation of 11-α-hydroxyandrosta-1,4-diene-3,17-dione (2) and 1,4,9(11)-androstatriene-3,17-d ione (3) were investigated. With ethylenediamine as the catalyst refluxing 2 and nitromethane the condensation s electively occurred at the 17-carbonyl and gave 11α-hydroxy-17-nitromethyl-ideneandrosta-1,4-diene-3-one in 60% yield no any reaction occurred at 3-carbonyl. With the same procedure the condensation of 2 and nitroethane exclus ively gave 11α,17β-dihydroxy-17α-ethylandrosta-1,4,8(14)-triene-3-one in 23% yield neither 17-nor 3-carbonyl nitroethylation product was obtained. In the presence of tosyl chloride and pyridine 2 was co nverted into 11α-p-to luenesulfonyloxyandrosta-1,4-diene-3,17-dione (4) in 94% yield. At 90 ℃ in the presence of potassium acetate and acetic anhydrid e 4 was eliminated and 3 was obt ained in 80% yield. Refluxing the mixture of nitromethane and 3 for 1 h, removing at least 10% of nitromethane via distillatio n, treating the residue with ethylenediamine, and refluxing the mixture for anot her 1 h gave specifically 1 in 96% yield. Refluxing the mixture of 3, notromethane and ethylenediamine the cond ensation gave 17-nitrome thylidene-1,3,11(12)-androstatriene-3-one (5) in 45% yield. Under the same conditions and increasing the amount of ethylenediamine t he simultaneously nitromethylation of 3-and 17-carbonyl of 3 resulted in 1 and 5 in 50% and 40% yield, respectively. Refluxing the mixture of 3, notroethane and ethylenediamine the condensation gave 17β-hydroxy-17α-ethyl-androsta-1,4,8(14),9(11)-tetraene-3-one in 17% yield.