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A Flexible Approach to Grandisine Alkaloids: Total Synthesis of Grandisines B, D, and F
Author(s) -
Kurasaki Haruaki,
Okamoto Iwao,
Morita Nobuyoshi,
Tamura Osamu
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200901843
Subject(s) - iminium , stereoselectivity , moiety , chemistry , stereochemistry , ring (chemistry) , total synthesis , intramolecular force , imine , amine gas treating , combinatorial chemistry , ion , organic chemistry , catalysis
This article describes in detail the first total synthesis of grandisine alkaloids, grandisines B, D, and F, which show affinity for the human δ‐opioid receptor. The key steps in this synthesis are construction of the isoquinuclidinone moiety of 2 by intramolecular imine formation and the tetracyclic ring system of 4 by stereoselective ring closure of the enolate of amine 8 generated by 1,4‐addition of ammonia to 9 . Synthesis of key intermediate 9 featured a highly stereoselective Brønsted acid mediated Morita–Baylis–Hillman (MBH) reaction via the N ‐acyl iminium ion.