Bioinspired Asymmetric Synthesis of Hispidanin A.
The first enantiospecific synthesis of hispidanin A (4), a dimeric diterpenoid from the rhizomes of Isodon hispida, was achieved with a longest linear sequence of 12 steps in 6.5 % overall yield. A key component is the use of the abundant and naturally occurring diterpenoids (+)-sclareolide and (+)-sclareol as starting materials, which enables the gram-scale preparation of the key intermediates totarane (1) and s-trans-12E,14-labdadien-20,8β-olide (2). Subsequently a thermal or an erbium-catalyzed intermolecular Diels-Alder reaction of totarane (1) with labdadienolide (2) provide convergent and rapid access to the natural product hispidanin A (4). The synthetic studies have offered significant impetus for the efficient construction of these architecturally complex natural products.
Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Fuzhuo
F
Li
Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Qian
Q
Tu
Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Sijia
S
Chen
School of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400030, China.
Lei
L
Zhu
School of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 400030, China.
Yu
Y
Lan
Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Jianxian
J
Gong
Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.|Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Science, College of Chemistry and Molecular Engineering, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.|Laboratory for Marine Drugs and Bioproducts of Qingdao, National Laboratory for Marine Science and Technology, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.
Zhen
Z
Yang
D004224:Diterpenes / Q000138:chemical synthesis* / Q000145:classification; D037602:Isodon / Q000737:chemistry; D015394:Molecular Structure; D027343:Rhizome / Q000737:chemistry
D004224:Diterpenes
Diels-Alder reaction; asymmetric synthesis; biosynthesis; hispidanin A; natural products