{Reference Type}: Journal Article
{Title}: Total synthesis of 1,4a-di-epi-ent-pancratistatin, exemplifying a stereodivergent approach to pancratistatin isomers.
{Author}: Sun C;Inokuma T;Tsuji D;Yamaoka Y;Akagi R;Yamada KI;
{Journal}: Chem Commun (Camb)
{Volume}: 60
{Issue}: 53
{Year}: 2024 Jun 27
{Factor}: 6.065
{DOI}: 10.1039/d4cc02199a
{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.