January 24, 2023


January 24, 2023

Anti-HIV macrocyclic daphnane orthoester diterpenoids from Daphne pedunculata

A research group led by Professor Wei Li of the Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Toho University, in collaboration with Shenyang Pharmaceutical University in China and Duke University Medical Centre in the United States, discovered for the first time that Daphne pedunculata (Thymelaeaceae) contains a substance inhibiting replication of human immunodeficiency virus (HIV). Further research is expected to lead the discovery of drugs with superior anti-HIV activity. It is expected that further research could potentially lead to the discovery of new drugs with superior anti-HIV activity for HIV treatment. The results of this research were published in the “Journal of Natural Products” of the American Chemical Society (ACS) on December 14, 2022, and were also selected as the cover illustration for the issue.
From left: Dr. Wei Li, Ms. Kouharu Otsuki, Mr. Lingjian Tan, Ms. Mi Zhang, Dr. Takashi Kikuchi
Key Points:
  • Daphne pedunculata, belonging to the Thymelaeaceae family, contains macrocyclic daphnane orthoesters that have potent anti-HIV activity.
  • This is the first to report on the anti-HIV macrocyclic daphnane orthoesters isolated from D. pedunculata.
  • Further elucidation of the anti-HIV macrocyclic daphnane orthoesters in plant of Thymelaeaceae is expected to contribute to the discovery of new anti-HIV drugs.
The Thymelaeaceae family consists of 53 genera and more than 800 species widely distributed throughout the world except in the arctic zone. Plants of this family characteristically contain daphnane and tigliane diterpenoids (Note 1), which have excellent biological activities, such as anti-cancer and anti-HIV activity. Macrocyclic daphnane orthoesters have excellent anti-HIV activity by eliminating latent HIV-infected cells and are attracting attention as potential novel treatment candidates for against HIV infection, which are different from existing anti-HIV drugs. Daphne pedunculata belongs to the family Thymelaeaceae that is distributed exclusively in Yunnan Province, China. This plant is an evergreen shrub and the yellow flowers bloom between November and December. In this study, a research group isolated 12 macrocyclic daphnane-type diterpenoids, including six new compounds, from D. pedunculata and elucidated their anti-HIV activity. The results of this study have deepened our knowledge of the structure–activity relationship of macrocyclic daphnane orthoesters. These findings are expected to lead to the discovery of new drugs for the treatment of HIV infection.

(Note 1) Diterpenoids
A class of terpene composed of four isoprene units and biosynthesized using geranylgeranyl diphosphate (GGPP) as a precursor. Diterpenes are officially defined as hydrocarbons; therefore, diterpenes with heteroatom-containing functional groups are called diterpenoids.

(Note2) Macrocyclic daphnane orthoester
Among diterpenoids, daphnane-type diterpenoids are compounds characterized by a 5/7/6-membered ring backbone with isopropenyl group. Macrocyclic daphnane orthoesters are compounds with a macrocyclic structure in which the aliphatic chain is linked to the five-membered ring part of the daphnane skeleton via orthoester moiety.

Figure 1. Sturcture of macrocyclic daphnane orthoesters isolated from Daphne pedunculata.

Journal Journal of Natural Products, December 14, 2022.

Daphnepedunins A–F: Anti-HIV Macrocyclic Daphnane Orthoester Diterpenoids from Daphne pedunculata

Lingjian Tan, Kouharu Otsuki, Mi Zhang, Takashi Kikuchi, Misaki Okayasu, Isao Azumaya, Di Zhou, Ning Li, Li Huang, Chin-Ho Chen, Wei Li*



@ Toho University