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Five Step Total Synthesis of Lythranidine
Author(s) -
Magann Nicholas L.,
Blyth Mitchell T.,
Sherburn Michael S.
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202107524
Subject(s) - stereocenter , natural product , diastereomer , total synthesis , chemistry , intermolecular force , combinatorial chemistry , biomimetic synthesis , hydride , stereochemistry , enantioselective synthesis , organic chemistry , molecule , catalysis , metal
A concise synthesis of the alkaloid lythranidine is reported. The strategy exploits the target's local C 2 symmetry by adopting a two directional synthetic approach, first in an acyclic environment, then in a cyclic system and finally in a bridged macrocyclic domain. The latter phase of the synthesis, which installs all four stereocenters, involves a thermodynamically controlled, twofold intermolecular/transannular aza‐Michael addition and a twofold hydride reduction. The synthesis is one third of the length of the most step‐economic previous approach, providing access to gram quantities of the natural product. The broad‐spectrum nature of the synthesis is demonstrated through the preparation of three diastereomeric analogues of the natural product.