Chirality 1 Three Sesquiterpenoid Dimers from Chloranthus japonicus . Absolute Configuration of Chlorahololide A and Related Compounds

The genus Chloranthus (Chloranthaceae) is mainly distributed over the east of Asia, and it comprises 13 species and five varieties in China. Chloranthus japonicus Sieb (‘yin-xian-cao’ in Chinese) has been long used in traditional Chinese medicine for the treatment of bone fractures, trauma, rheumatism, and cough. The previous phytochemical investigations on this plant have resulted in the isolation of a number of sesquiterpenoid dimers. Some of them were reported to show multi-biological activities, such as antifungal, potent and selective tumor growth-inhibitory, inhibition of cell adhesion molecule expression and tyrosinase. As part of our ongoing search for new bioactive natural products from the traditional Chinese herbal medicines in the Qinba Mountains, chemical studies of the whole plant of C. japonicus were carried out, leading to the discovery of a new sesquiterpenoid dimer, named multistalide C (1), together with two known compounds, shizukaols C and D (2 and 3) (Chart 1). Herein, we describe the isolation, structural identification, including the absolute configuration, and brine shrimp larvae toxicity of the three compounds. Since compound 1 is structurally related to chlorahololide A (4), this latter compound was also reconsidered. In fact, the absolute configuration of chlorahololide A and several related sesquiterpenoid dimers has been assigned using the exciton chirality method, but without the necessary prerequisites for the application of this well-known approach. The limitations of the exciton chirality method for this family of chlorahololide analogues are discussed in details.