Ren L,
Lu Z,
Wu D,
Ma M,
Li A *.
Shanghai Institute of Organic Chemistry and University of Chinese Academy of Sciences,
Shanghai, P. R. China
Total Synthesis of Paxdaphnine A and Daphlongamine B via Aza-Prins Cyclization Strategy.
J. Am. Chem. Soc. 2025;
147: 27137-27142
DOI:
10.1021/jacs.4c04779
Keywords
(±)-paxdaphnine A - (±)-paxdaphnine B - Suzuki–Miyaura cross coupling - Kumada cross-coupling
- Swern oxidation - nitrone dipolar cycloaddition - Pauson–Khand reaction - aza-Prins
reaction
Significance
Li and co-workers report the first total synthesis of the daphniphyllum alkaloids
(±)‑paxdaphnines A and B and (±)-daphlongamine B. (±)‑Paxdaphnine A possesses a highly
congested heptacyclic scaffold with eight consecutive stereocenters. Pivotal for the
successful construction of the molecule’s core were a nitrone dipolar cycloaddition
and a Pauson–Khand reaction.
Comment
The synthesis commenced with coupling of enone A with alkene B. Effective decoration of the cycloheptane in D furnished oxime G in seven steps. Reduction of G and subsequent dioxolane deprotection generated directly a putative nitrone which,
when heated in PhMe, gave isoxazole H. N–O bond reduction and elimination gave enyne I, which smoothly underwent Pauson–Khand reaction. (±)-Paxdaphnine B, accessed from
enone J through functional group interconversions, was converted into (±)-paxdaphnine A by
aza-Prins reaction.
