Citation: Ming-Zhu Zhu, Ze-Jun Xu, Jiao-Zhen Zhang, Li-Zhi Shi, Zong-Xu Gao, Yi Li, Shuang-Zhi Yuan, Yan-Rong Ma, Ai-Xia Cheng, Hong-Xiang Lou. Haploides A–G: Diterpenoids featuring four new carbon skeletons via non-carbocation-driven skeletal diversification[J]. Chinese Chemical Letters, ;2026, 37(7): 111584. doi: 10.1016/j.cclet.2025.111584 shu

Haploides A–G: Diterpenoids featuring four new carbon skeletons via non-carbocation-driven skeletal diversification

Ming-Zhu Zhu ^{a, d, 1} ,
Ze-Jun Xu ^{a, b, 1} ,
Jiao-Zhen Zhang ^a ,
Li-Zhi Shi ^a ,
Zong-Xu Gao ^a ,
Yi Li ^a ,
Shuang-Zhi Yuan ^a ,
Yan-Rong Ma ^a ,
Ai-Xia Cheng ^a ,
Hong-Xiang Lou ^{a, b, c, *,}

a.
Department of Natural Products Chemistry, Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Ji'nan 250012, China
b.
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shandong University, Ji'nan 250012, China
c.
Joint research institute of Medical and Pharmaceutical Sciences, Qilu Hospital, Shandong University, and Shandong Maternal and Child Care Hospital, Ji'nan 250012, China
d.
Department of Pharmacy, The Second Hospital, Cheeloo College of Medicine, Shandong University, Ji'nan 250033, China

louhongxiang@sdu.edu.cn

Received Date: 7 May 2025
Revised Date: 8 July 2025
Accepted Date: 11 July 2025
Available Online: 11 July 2025

Figures(4)

A series of highly rearranged labdane diterpenoids featuring previously unreported skeletons, including 9,18-cyclolabdanes (1 and 2), 1,10-seco-9,18-cyclolabdanes (3–5), 7,18-cyclolabdanes (6), and 1,10-seco-1,5-cyclolabdanes (7), along with seven novel labdanes (8–14), two novel halimane diterpenoids (15 and 16), and three known congeners (17–19), were isolated from Chinese liverwort Haplomitrium mnioides. Their structures were unequivocally determined through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations. These diverse diterpenoids were biosynthesized through an aldol-type cascade process, using 19 as the starting material, distinguishing them from compounds generated via conventional carbocation rearrangement. Anti-inflammatory assays revealed that haploide O (15) and haplomitrenolide C (17) significantly inhibited the secretion of proinflammatory cytokines interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in vitro in concanavalin A (ConA)-induced murine spleen cells.
- Labdane diterpenoids,
- New carbon skeletons,
- Haplomitrium mnioides,
- Biosynthesis,
- Single-crystal X-ray diffraction,
- Anti-inflammatory activity
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