Abstract：
The total synthesis of 1,4a-di-epi-ent-pancratistatin, a novel stereoisomer of the anti-tumor Amaryllidaceae alkaloid pancratistatin, was achieved in 14 steps starting from D-mannitol. The construction of the pancratistatin skeleton involved conjugate addition of organocuprate to a nitrosoolefin, which was generated in situ from inosose oxime. This was followed by stereoselective reduction of the oxime to an amine and site-selective formylation. Biological evaluations revealed that the newly synthesized compounds exhibit cytotoxicity toward cancer cells and significant ferroptosis inhibitory activity. These compounds constitute a promising small-molecule library for the development of potent bioactive agents.
摘要：
1,4a-二-epi-ent-pancreatin的全合成，一种新的立体异构体的抗肿瘤石豆科生物碱pancratistatin，从D-甘露醇开始，共14个步骤。pancratistatin骨架的构建涉及有机铜酸盐与亚硝基烯烃的共轭加成，它是由尿糖肟原位生成的。随后将肟立体选择性还原为胺和位点选择性甲酰化。生物学评估表明，新合成的化合物对癌细胞具有细胞毒性和显着的铁凋亡抑制活性。这些化合物构成了用于开发有效生物活性剂的有希望的小分子文库。
