Phương pháp tổng hợp exemestan từ họp chất androsta-1,4-dien-3,17-dion

Abstract

As regarding exemestane (1) as a 3rd-generation aromatase inhibitor widely used for treatment of hormone dependent breast cancer in postmenopausal women, it was synthesized with a 3-step method from androsta-1,4-diene-3,17-dione (2). Firstly, compound 2 was converted to 1,3-dipyrrolidinoandrosta-3,5-dien-17-on (3) and the intermediate product 3 was used immediately in the second step to afford 6-(hydroxymethyl)androsta-1,4-dien-3,17-dion (A), the combined yield of fist two steps was 77 %. In the final step, exemestane was archived from compound 4 with 88.2 % yield. The synthesis achieved the overall yield of 67.9 %. The structures of exemestane and intermediate products were confirmed by MS and NMR.