TY - JOUR
T1 - Evolution of a Unified Strategy for Complex Sesterterpenoids
T2 - Progress toward Astellatol and the Total Synthesis of (-)-Nitidasin
AU - Hog, Daniel T.
AU - Huber, Florian M.E.
AU - Jiménez-Osés, Gonzalo
AU - Mayer, Peter
AU - Houk, Kendall N.
AU - Trauner, Dirk
N1 - Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Astellatol and nitidasin belong to a subset of sesterterpenoids that share a sterically encumbered trans-hydrindane motif with an isopropyl substituent. In addition, these natural products feature intriguing polycyclic ring systems, posing significant challenges for chemical synthesis. Herein, the evolution of our stereoselective strategy for isopropyl trans-hydrindane sesterterpenoids is detailed. These endeavors included the synthesis of several building blocks, enabling studies toward all molecules of this terpenoid subclass, and of advanced intermediates of our initial route toward a biomimetic synthesis of astellatol. These findings provided the basis for a second-generation and a third-generation approach toward astellatol that eventually culminated in the enantioselective total synthesis of (-)-nitidasin. In particular, a series of substrate-controlled transformations to install the ten stereogenic centers of the target molecule was orchestrated and the carbocyclic backbone was forged in a convergent fashion. Furthermore, the progress toward the synthesis of astellatol is disclosed and insights into some observed yet unexpected diastereoselectivities by detailed quantum-mechanical calculations are provided. Two and a half molecules: Astellatol and nitidasin are polycyclic sesterterpenoids, posing considerable challenges for synthetic chemists. In this full account, the evolution of a synthetic strategy for these and structurally related natural products is given (see scheme). The presented work includes efforts toward a biomimetic synthesis of astellatol, a successful route for the first total synthesis of (-)-nitidasin, and quantum-mechanical investigations into unexpected diastereosectivities.
AB - Astellatol and nitidasin belong to a subset of sesterterpenoids that share a sterically encumbered trans-hydrindane motif with an isopropyl substituent. In addition, these natural products feature intriguing polycyclic ring systems, posing significant challenges for chemical synthesis. Herein, the evolution of our stereoselective strategy for isopropyl trans-hydrindane sesterterpenoids is detailed. These endeavors included the synthesis of several building blocks, enabling studies toward all molecules of this terpenoid subclass, and of advanced intermediates of our initial route toward a biomimetic synthesis of astellatol. These findings provided the basis for a second-generation and a third-generation approach toward astellatol that eventually culminated in the enantioselective total synthesis of (-)-nitidasin. In particular, a series of substrate-controlled transformations to install the ten stereogenic centers of the target molecule was orchestrated and the carbocyclic backbone was forged in a convergent fashion. Furthermore, the progress toward the synthesis of astellatol is disclosed and insights into some observed yet unexpected diastereoselectivities by detailed quantum-mechanical calculations are provided. Two and a half molecules: Astellatol and nitidasin are polycyclic sesterterpenoids, posing considerable challenges for synthetic chemists. In this full account, the evolution of a synthetic strategy for these and structurally related natural products is given (see scheme). The presented work includes efforts toward a biomimetic synthesis of astellatol, a successful route for the first total synthesis of (-)-nitidasin, and quantum-mechanical investigations into unexpected diastereosectivities.
KW - computational chemistry
KW - natural products
KW - stereoselective synthesis
KW - terpenoids
KW - total synthesis
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U2 - 10.1002/chem.201501423
DO - 10.1002/chem.201501423
M3 - Article
C2 - 26300211
AN - SCOPUS:84941599149
SN - 0947-6539
VL - 21
SP - 13646
EP - 13665
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 39
ER -