Pierre. Crabbe

Long-acting contraceptive agents: Design of the who chemical synthesis programme

The great demand for improved long-acting injectable steroid contraceptives, particularly in developing countries, and the relative lack of interest from the pharmaceutical industry to develop such products stimulated WHO to launch a synthetic and screening programme to find improved, safe and acceptable injectable preparations. More than 210 esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) and levonorgestrel (D-(-)-13 beta-ethyl-17 alpha-ethynyl-17 beta-hydroxygon-4-en-3-one) have been prepared in university-based research laboratories situated mainly in developing countries, and then screened by NICHHD in animal models. The following three compounds, levonorgestrel butanoate, cyclopropylcarboxylate and cyclobutylcarboxylate, proved to be particularly long-acting when administered as microcrystalline suspensions. The overall strategy of this research and development programme is described.

Steroids cclix. The synthesis of 5β,19 and 6β,19-cyclo steroids

Abstract The solvolysis of 3β,19-dihydroxyandrost-5-ene-17-one-3-acetate 19-tosylate (Ib) led to the Δ6-5, 19-cyclo steroid IIa or a variety of 6α-substituted 5,19-cyclopropanes V depending upon the reaction conditions. The possibility that these reactions proceed through an intermediate homoallylic bridged cation is discussed. The formation of 6β,19-cyclobutanes from 19-hydroxyandrost-4-ene 3,17-dione tosylate (VIb) is described