Universidad del Papaloapan, Tuxtepec, Oaxaca 68301, Mexico.
Posgrado en Ciencias Químicas. Benemérita, Universidad Autónoma de Puebla, 72570 Puebla, Pue, Mexico.
Steroids. 2021 Feb;166:108777. doi: 10.1016/j.steroids.2020.108777. Epub 2020 Dec 10.
In this work, we report the synthesis of two new azasteroids through the modification of the A and B rings of diosgenin 1. The 4-azasteroid derivative 12 was prepared in three steps using the α,β-insaturated-3-keto compound 11 as a precursor, which was first oxidized with KMnO/KIO followed by an oxidative cleavage of ring A, and subsequently cyclized with an ammonium salt, under focused microwave irradiation for a short time of 3 min. A second azasteroid was synthesized, for which the key step was the Beckmann rearrangement of ring B of the oxime 16, affording the lactam-type enamide 17 in good yield. The methodologies developed for the synthesis of the precursors derivatives 10 and 11 contribute to improved yields, compared to those reported in the literature. The biological activity of the azasteroidal compounds 12 and 17 and their precursors has been evaluated in cervical cancer cells (HeLa), colon (HCT-15), and triple negative breast cancer (MDA-MB-231) lines.
在这项工作中，我们通过修饰薯蓣皂苷元 1 的 A 环和 B 环，合成了两种新的氮杂甾体。以α,β-不饱和-3-酮化合物 11 为前体，经过三步反应得到 4-氮杂甾体衍生物 12，首先用 KMnO/KIO 氧化，然后进行 A 环的氧化裂解，随后在聚焦微波辐射下，在 3 分钟的短时间内用铵盐环化。合成了第二种氮杂甾体，其关键步骤是肟 16 的贝克曼重排，得到了具有良好收率的内酰胺型烯酰胺 17。与文献报道的方法相比，为合成前体衍生物 10 和 11 而开发的方法有助于提高产率。已经评估了氮杂甾体化合物 12 和 17 及其前体在宫颈癌（HeLa）、结肠癌（HCT-15）和三阴性乳腺癌（MDA-MB-231）细胞系中的生物活性。
