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Asymmetric Total Synthesis of Onoseriolide, Bolivianine, and Isobolivianine
Author(s) -
Du Biao,
Yuan Changchun,
Yu Tianzi,
Yang Li,
Yang Yang,
Liu Bo,
Qin Song
Publication year - 2014
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.201304378
Subject(s) - intramolecular force , total synthesis , cyclopropanation , chemistry , allylic rearrangement , stereochemistry , cascade , stereoselectivity , combinatorial chemistry , catalysis , organic chemistry , chromatography
Abstract In this article, we describe our efforts on the total synthesis of bolivianine ( 1 ) and isobolivianine ( 2 ), involving the synthesis of onoseriolide ( 3 ). The first generation synthesis of bolivianine was completed in 21 steps by following a chiral resolution strategy. Based on the potential biogenetic relationship between bolivianine ( 1 ), onoseriolide ( 3 ), and β‐( E )‐ocimene ( 8 ), the second generation synthesis of bolivianine was biomimetically achieved from commercially available (+)‐verbenone in 14 steps. The improved total synthesis features an unprecedented palladium‐catalyzed intramolecular cyclopropanation through an allylic metal carbene, for the construction of the ABC tricyclic system, and a Diels–Alder/intramolecular hetero‐Diels–Alder (DA/IMHDA) cascade for installation of the EFG tricyclic skeleton with the correct stereochemistry. Transformation from bolivianine to isobolivianine was facilitated in the presence of acid. The biosynthetic mechanism and the excellent regio‐ and endo selectivities in the cascade are well supported by theoretical chemistry based on the DFT calculations.