Toward the Synthesis of Pestalustaine A: Structural Revision and Formation of Original Strained Tricyclic Architectures
Abstract
We report our quest toward the total synthesis of the reported structure of the sesquiterpene pestalustaine A and its unprecedented tricyclic skeleton. Our retrosynthesis involved a transannular Michael addition of a 1,3‐keto‐ester and enal‐containing bicyclo[4.4.1]undec‐3‐ene obtained from the ring expansion of a chiral γ,γ−disubstituted cyclohexanone and stereoselective Hosomi‐Sakurai reaction. Serendipity allowed us to uncover powerful divergent and unexpected cyclizations of this bicycle in ionic or oxidative conditions, giving access to complex tricyclic architectures such as tricyclo[5.2.1.1 2,5 ]undecane, octahydro‐1,5‐methanonaphthalene, octahydro‐12,6‐methanonaphthalene frameworks, and the octahydro‐1,5‐methanoazulene reported skeleton of pestalustaine A. The present synthetic study also led us to note a discrepancy between the reported structure of pestalustaine A and the 2D NMR data, which led us to propose a revised structure of the natural product to a caryophyllene‐type framework, a reassignment supported by computational prediction of NMR chemical shifts.
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BibTeX
@article{cao2026toward,
title = {{Toward the Synthesis of Pestalustaine A: Structural Revision and Formation of Original Strained Tricyclic Architectures}},
author = {Wei Cao and Alicia Ross and Jean‐pierre Baltaze and Régis Guillot and Menglin Xu and Rongzhen Qin and Bingcheng Yang and Isabel Wong and Katayoon Formul and Cyrille Kouklovsky and Dean Tantillo and Vincent Gandon and Guillaume Vincent},
journal = {Angewandte Chemie International Edition},
year = {2026},
month = jul,
doi = {10.1002/anie.7194437},
url = {https://universite-paris-saclay.hal.science/hal-05688259v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Toward the Synthesis of Pestalustaine A: Structural Revision and Formation of Original Strained Tricyclic Architectures
AU - Wei Cao
AU - Alicia Ross
AU - Jean‐pierre Baltaze
AU - Régis Guillot
AU - Menglin Xu
AU - Rongzhen Qin
AU - Bingcheng Yang
AU - Isabel Wong
AU - Katayoon Formul
AU - Cyrille Kouklovsky
AU - Dean Tantillo
AU - Vincent Gandon
AU - Guillaume Vincent
PY - 2026
DA - 2026/07/09
JO - Angewandte Chemie International Edition
DO - 10.1002/anie.7194437
UR - https://universite-paris-saclay.hal.science/hal-05688259v1
AB - We report our quest toward the total synthesis of the reported structure of the sesquiterpene pestalustaine A and its unprecedented tricyclic skeleton. Our retrosynthesis involved a transannular Michael addition of a 1,3‐keto‐ester and enal‐containing bicyclo[4.4.1]undec‐3‐ene obtained from the ring expansion of a chiral γ,γ−disubstituted cyclohexanone and stereoselective Hosomi‐Sakurai reaction. Serendipity allowed us to uncover powerful divergent and unexpected cyclizations of this bicycle in ionic or oxidative conditions, giving access to complex tricyclic architectures such as tricyclo[5.2.1.1 2,5 ]undecane, octahydro‐1,5‐methanonaphthalene, octahydro‐12,6‐methanonaphthalene frameworks, and the octahydro‐1,5‐methanoazulene reported skeleton of pestalustaine A. The present synthetic study also led us to note a discrepancy between the reported structure of pestalustaine A and the 2D NMR data, which led us to propose a revised structure of the natural product to a caryophyllene‐type framework, a reassignment supported by computational prediction of NMR chemical shifts.
SN - 1433-7851
SN - 1521-3773
ER -