Total Synthesis of Maoecrystal P: Application of a Strained Bicyclic Synthon
Fan Su
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 China
These authors contributed equally.
Search for more papers by this authorYandong Lu
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 China
These authors contributed equally.
Search for more papers by this authorLingran Kong
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 China
Search for more papers by this authorJingjing Liu
Peking-Tsinghua Center for Life Sciences, Academy of Advanced Interdisciplinary Studies, Peking University, Beijing, 100871 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Tuoping Luo
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 China
Peking-Tsinghua Center for Life Sciences, Academy of Advanced Interdisciplinary Studies, Peking University, Beijing, 100871 China
Search for more papers by this authorFan Su
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 China
These authors contributed equally.
Search for more papers by this authorYandong Lu
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 China
These authors contributed equally.
Search for more papers by this authorLingran Kong
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 China
Search for more papers by this authorJingjing Liu
Peking-Tsinghua Center for Life Sciences, Academy of Advanced Interdisciplinary Studies, Peking University, Beijing, 100871 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Tuoping Luo
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871 China
Peking-Tsinghua Center for Life Sciences, Academy of Advanced Interdisciplinary Studies, Peking University, Beijing, 100871 China
Search for more papers by this authorGraphical Abstract
Less is not always more: A strategy involving the incorporation of a substituted cyclopropane ring to generate an overbred intermediate was devised for the total synthesis of the highly oxidized bioactive ent-kauranoid maoecrystal P. Starting from a strained bicyclo[4.1.0] ketone, a sequence based on intermolecular Diels–Alder cycloaddition, allylic oxidation, SmI2-mediated cyclization, and late-stage oxidation reactions led to the target molecule.
Abstract
A new strategy was devised for the total synthesis of highly oxidized ent-kauranoids. A highly regio- and diastereoselective intermolecular Diels–Alder cycloaddition involving a diene embedded in a substituted bicyclo[4.1.0] skeleton was used to assemble all carbon centers but C17 of the target molecule at an early stage of the synthesis. Subsequent synthetic steps, including redox manipulations, SmI2-mediated cyclization, and isomerization reactions, afforded the antitumor natural product maoecrystal P.
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