A Convenient Synthesis Of (16S,20S)-3β-Hydroxy-5α-Pregnane-20,16-Carbolactam And Its N-Alkyl Derivatives

The study described a concise synthesis of (16S,20S)-3β-hydroxy-5α-pregnane-20,16-carbolactam and its N-alkyl derivatives from tigogenin, achieving high yields through a process involving lactone ring-opening with an aminoalane reagent, followed by oxidation and cyclization. Various methods, including reductive amination and microwave-assisted reactions, were employed to produce the lactam and its derivatives. The configurations at stereogenic centers were confirmed by NOE and ROESY experiments. The synthesis yielded different derivatives, such as 3-TBS lactam 4b and 3-hydroxy-lactam 4a, with yields of 73% and 14%, respectively. Two alternative methods for synthesizing bisnorcholanic lactams were also described, with the first method being more efficient and stereoselective, producing the desired lactam in a quantitative yield. Further studies were planned to explore the application of these lactams in synthesizing steroidal alkaloids and evaluating their biological activity.