Resolution of δ-Lactams Provides Access to Nonracemic Benzoquinolinones: The Synthesis of LY300502 and LY300503

摘要

Recently, LY191704 (1) was synthesized and identified as a selective, potent, noncompetitive type Ⅰ inhibitor of 5-α-reductase in cell cultures derived from human foreskin fibroblasts. This activity may be useful in the development of new drugs for the treatment of acne, male pattern baldness, benign prostatic hyperplasia, or pros-tatic cancer and may augment the utility of finasteride (2). As part of the development portfolio for this new drug, a reliable and efficient process for the preparation of large amounts of 1 was required. In addition, the enantiomers of 1, LY300502 (3) and LY300503 (4), were required for preclinical evaluation and potential commercial development.