Bioinspired Asymmetric Synthesis of Hispidanin A

Angewandte Chemie - International Edition

5 years ago

Bioinspired Asymmetric Synthesis of Hispidanin A

Fuzhuo Li, Yu Lan, Jianxian Gong, Qian Tu, Lei Zhu, Sijia Chen, Zhen Yang

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. When two become one: An enantiospecific synthesis of hispidanin A, a dimeric diterpenoid from Isodon hispida, was achieved with a longest linear sequence of 12 steps and 6.5 % overall yield. Key component are the use of the diterpenoids (+)-sclareolide and (+)-sclareol as starting materials to prepare the key intermediates totarane (1) and labdadienolide (2), and intermolecular Diels–Alder reaction of 1 with 2 to give hispidanin A.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201700838