110.Bioinspired Asymmetric Synthesis of Hispidanin A

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

Angew.Chem. Int. Ed. 2017, 56,5844

• Selected as Hot Paper in Natural Products

• Highlighted in Synfacts, 2017, 13, 569.

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.