Toward the Synthesis of Pestalustaine A: Structural Revision and Formation of Original Strained Tricyclic Architectures

W Wei Cao (State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering) A Alicia Ross (Department of Chemistry University of California Davis Davis California USA) J Jean‐Pierre Baltaze (Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO) Orsay France) R Régis Guillot (Institut de Chimie Moléculaire et des Matériaux d’Orsay, CNRS) M Menglin Xu (State Key Laboratory of Chemical Safety College of Chemistry and Chemical Engineering China University of Petroleum (East China) Qingdao People's Republic of China) R Rongzhen Qin (State Key Laboratory of Chemical Safety College of Chemistry and Chemical Engineering China University of Petroleum (East China) Qingdao People's Republic of China) B Bingcheng Yang (State Key Laboratory of Chemical Safety College of Chemistry and Chemical Engineering China University of Petroleum (East China) Qingdao People's Republic of China) I Isabel Wong (Sacramento City College Sacramento California USA) K Katayoon Formul (Sacramento City College Sacramento California USA) C Cyrille Kouklovsky (Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO) Orsay France) D Dean J. Tantillo (Department of Chemistry, University of California Davis, One Shields Ave. Davis, Sacramento, California 95616, United States) V Vincent Gandon G Guillaume Vincent (Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO) Orsay France)

Abstract

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.

Article Details

Volume / Issue Vol. 1, Issue 1
Published July 09, 2026
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (13)

W

Wei Cao

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering

A

Alicia Ross

Department of Chemistry University of California Davis Davis California USA

J

Jean‐Pierre Baltaze

Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO) Orsay France

R

Régis Guillot

Institut de Chimie Moléculaire et des Matériaux d’Orsay, CNRS

M

Menglin Xu

State Key Laboratory of Chemical Safety College of Chemistry and Chemical Engineering China University of Petroleum (East China) Qingdao People's Republic of China

R

Rongzhen Qin

State Key Laboratory of Chemical Safety College of Chemistry and Chemical Engineering China University of Petroleum (East China) Qingdao People's Republic of China

B

Bingcheng Yang

State Key Laboratory of Chemical Safety College of Chemistry and Chemical Engineering China University of Petroleum (East China) Qingdao People's Republic of China

I

Isabel Wong

Sacramento City College Sacramento California USA

K

Katayoon Formul

Sacramento City College Sacramento California USA

C

Cyrille Kouklovsky

Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO) Orsay France

D

Dean J. Tantillo

Department of Chemistry, University of California Davis, One Shields Ave. Davis, Sacramento, California 95616, United States

V

Vincent Gandon

G

Guillaume Vincent

Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO) Orsay France