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Synthesis of Epibatidine Analogues by Pyrrole Diels–Alder Reactions: Rapid Access to Azabicyclo[2.2.1]heptane and 3,8‐Diazabicyclo[3.2.1]octane Scaffolds for Library Synthesis
Author(s) -
Murray Alexander T.,
Packard Emma,
Nortcliffe Andrew,
Lewis William,
Hamza Daniel,
Jones Geraint,
Moody Christopher J.
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201601177
Subject(s) - epibatidine , chemistry , heptane , bicyclic molecule , ozonolysis , octane , intramolecular force , amination , reductive amination , diels–alder reaction , combinatorial chemistry , pyrrole , methyllycaconitine , dabco , stereochemistry , organic chemistry , nicotinic agonist , nicotinic acetylcholine receptor , catalysis , receptor , biochemistry
Analogues of the nicotinic acetylcholine antagonist epibatidine, suitable for diversification, were synthesized by application of a pyrrole Diels–Alder strategy, allowing rapid generation of azabicyclo[2.2.1]heptane bicyclic cores. Further molecular complexity could be accessed by using intramolecular Diels–Alder reactions, or ring expansion by ozonolysis–reductive amination chemistry. Scaffolds were designed such that they could be orthogonally deprotected, yielding three points of diversity for library synthesis, exemplified by 24 compounds synthesized from four cores.