%0 Journal Article
%T Total synthesis of 1,4a-di-epi-ent-pancratistatin, exemplifying a stereodivergent approach to pancratistatin isomers.
%A Sun C
%A Inokuma T
%A Tsuji D
%A Yamaoka Y
%A Akagi R
%A Yamada KI
%J Chem Commun (Camb)
%V 60
%N 53
%D 2024 Jun 27
%M 38864269
%F 6.065
%R 10.1039/d4cc02199a
%X 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.