Yu Shaopeng, Zhang Qiuheng, Zhong Xueqing, Wang Chao, Shi Wenqing, Zhuang Jiahua, Zhang Rui, Jin Fangjie, Zhang Jiange, Zhao Qunfei, Chen Gu-Zhou, Ye Wenbo, Lin Guo-Qiang
The Research Center of Chiral Drugs, Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Shanghai 200032, China.
Org Lett. 2024 Nov 15;26(45):9704-9709. doi: 10.1021/acs.orglett.4c03433. Epub 2024 Nov 4.
A chemoenzymatic synthesis access to resibufogenin and bufalin was developed in seven steps without protecting groups. Starting with androstenedione (AD), an α-OH was introduced directly at C14 by hydroxylase P-450, which was further used as the directing group for hydrogenation to fully control the C17 configuration in the β-orientation after Suzuki cross-coupling. Dehydration of 14α-OH followed by an epoxidation delivered resibufogenin. Simultaneously, bufalin was also obtained via a challenging anaerobic Mukaiyama hydration.
开发了一种七步无保护基的化学酶法合成途径来制备脂蟾毒配基和蟾毒灵。以雄烯二酮（AD）为起始原料，通过细胞色素P-450羟化酶在C14位直接引入α-OH，该α-OH进一步用作氢化的导向基团，以在铃木交叉偶联后完全控制C17位的β构型。14α-OH脱水后进行环氧化反应得到脂蟾毒配基。同时，还通过具有挑战性的厌氧向山加水反应获得了蟾毒灵。
