TY - JOUR
T1 - Divergent Total Syntheses of 7,20-Epoxy, 3,20-Epoxy, and 6,7-seco-ent-Kaurane Diterpenoids
AU - Wang, Bo
AU - Ma, Wenjing
AU - Zhuang, Andrew-Go
AU - Luo, Han
AU - Zhu, Lizhi
AU - Han, Wei
AU - Lee, Chi-Sing
N1 - B.W. and W.M. contributed equally to this work. This work is financially supported by the National Natural Science Foundation of China (grant no. 22471231), University Grants Committee of Hong Kong (GRF 12301320 and 12303821), Peking University Shenzhen Graduate School and Hong Kong Baptist University. A special thanks to Prof. Wing-Tak Wong (Hong Kong Polytechnic University) for the X-ray crystallography of (±)-12, (±)-17, (±)-15-epi-enmelol, and (±)-neolaxiflorin.
Publisher copyright:
© 2025 The Author(s). European Journal of Organic Chemistry published by Wiley-VCH GmbH
PY - 2025/6/3
Y1 - 2025/6/3
N2 - The genus Isodon is a well-known traditional medicinal herb that serves as a rich source of cytotoxic ent-kaurane diterpenoids, which bear the same tetracyclic core of ent-kaurane with different oxygenation, bond-cleavage, and rearrangement patterns. The 7,20-epoxy-ent-kaurane diterpenoids are the most studied subclasses, which show promising anticancer activities. Moreover, they also have the potential for transforming to other subclasses of ent-kaurane diterpenoids. Herein, the details of this study on developing a highly diastereoselective synthetic strategy for the 7,20-epoxy-ent-kaurane diterpenoid (5 natural products) and its conversion to the 3,20-epoxy (2 natural products) and 6,7-seco derivatives (2 natural products) are reported. The synthetic strategy features a thermal Diels–Alder cycloaddition for the construction of the AB ring system, an intramolecular Mukaiyama Michael/carbocyclization cascade reaction for establishing the CD ring system, a site-stereoselective oxidation/reduction strategy for completion of the total syntheses of several representative 7,20-epoxy-ent-kaurane diterpenoids, and the divergent syntheses of Isodon diterpenoids in the 3,20-epoxy and 6,7-seco subclasses via bioinspired strategies.
AB - The genus Isodon is a well-known traditional medicinal herb that serves as a rich source of cytotoxic ent-kaurane diterpenoids, which bear the same tetracyclic core of ent-kaurane with different oxygenation, bond-cleavage, and rearrangement patterns. The 7,20-epoxy-ent-kaurane diterpenoids are the most studied subclasses, which show promising anticancer activities. Moreover, they also have the potential for transforming to other subclasses of ent-kaurane diterpenoids. Herein, the details of this study on developing a highly diastereoselective synthetic strategy for the 7,20-epoxy-ent-kaurane diterpenoid (5 natural products) and its conversion to the 3,20-epoxy (2 natural products) and 6,7-seco derivatives (2 natural products) are reported. The synthetic strategy features a thermal Diels–Alder cycloaddition for the construction of the AB ring system, an intramolecular Mukaiyama Michael/carbocyclization cascade reaction for establishing the CD ring system, a site-stereoselective oxidation/reduction strategy for completion of the total syntheses of several representative 7,20-epoxy-ent-kaurane diterpenoids, and the divergent syntheses of Isodon diterpenoids in the 3,20-epoxy and 6,7-seco subclasses via bioinspired strategies.
KW - Isodon
KW - bioinspired strategies
KW - cascade cyclizations
KW - divergent syntheses
KW - ent -kaurane diterpenoids
UR - http://www.scopus.com/inward/record.url?scp=105005096739&partnerID=8YFLogxK
U2 - 10.1002/ejoc.202500156
DO - 10.1002/ejoc.202500156
M3 - Journal article
SN - 1434-193X
VL - 28
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
IS - 21
M1 - e202500156
ER -
