Diastereoisomeric macrocyclic polydisulfides from the mangrove Bruguiera gymnorrhiza Xiao-Ying Huang a , Qi Wang a , Hai-Li Liu a , Yu Zhang a , Guo-Rong Xin b , Xu Shen a , Mei-Ling Dong b, * , Yue-Wei Guo a, * a State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zu Chong Zhi Rd. 555, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China b Institute of Biological Science, Sun Yat-Sen University, Xin Gang West Road 135, Guangzhouo 510275, PR China article info Article history: Received 29 May 2008 Received in revised form 26 March 2009 Available online xxxx Keywords: Bruguiera gymnorrhiza Rhizophoraceae Macrocyclic polydisulfide 3,3 0 -Dihydroxy-1,5,1 0 ,5 0 - tetrathiacyclodecane abstract The uncommon macrocyclic polydisulfides, trans-3,3 0 -dihydroxy-1,5,1 0 ,5 0 -tetrathiacyclodecane (1), cis- 3,3 0 -dihydroxy-1,5,1 0 ,5 0 -tetrathiacyclodecane (2), along with five known related cyclic disulfides, gym- norrhizol (3), neogymnorrhizol (4), bruguiesulfurol (5), brugierol (6), and isobrugierol (7), were isolated from the mangrove Bruguiera gymnorrhiza collected from Guangdong Province, China. Structures of com- pounds 1 and 2 were determined by extensive analysis of their spectroscopic data, by comparison of their NMR spectroscopic data with those of the co-occurring known compounds, as well as by single-crystal X- ray diffraction analysis. A possible biogenetic origin was also proposed. Ó 2009 Published by Elsevier Ltd. 1. Introduction Cyclic polysulfides are relatively uncommon in nature. Many exhibit interesting biological activities ranging from those of anti- cancer (Homhual et al., 2006), antifungal (Searle and Molinski, 1994), and antibacterial (Makarieva et al., 1995; Litaudon et al., 1994) agents to inhibitors of protein kinase C (Compagnone et al., 1994). Cyclic polysulfides have mainly been found in the mushroom Lentinus edodes (Morite and Kobayashi, 1976; Morite and Kobayashi, 1966), the red alga Chondria californica (Wratten and Faulkner, 1976), and in the tropical mangrove of the genus Bruguiera (family Rhizophoraceae) (Homhual et al., 2006; Kato and Takahashi, 1976; Kato and Numata, 1972; Loder and Russell, 1969). The mangrove, Bruguiera gymnorrhiza (L.) Savigny (Rhizophora- ceae), is widely distributed on seashores and edges throughout tropical Asia, southern and eastern Africa, and northern Australia (Hou, 1970). In Thailand, its flowers are used as a vegetable (Bunyapraphatsara, 2000). The fruits and bark of the title plant have also been used traditionally for treating diarrhea in mainland China (Bamroongrugsa, 1999), whereas its roots and leaves are used for treating burns (Othman, 1998). A previous investigation of the flowers of the title plant collected in Samutsongkram Prov- ince, Thailand, resulted in isolation of the cyclic disulfides, bruguie- sulfurol (5), brugierol (6) and isobrugierol (7)(Homhual et al., 2006). Some of these natural products also exhibited anti-tumor activity against HepG2 hepatoma cells, antibacterial activity against Lactobacillus acidophilus and Bacillus subtilis, and termicidal activity against Coptotermis formosanus (Homhual et al., 2006; Yoga et al., 1991; Kato, 1973), respectively. In the course of our search for bioactive secondary metabolites from mangroves along the Chinese coasts (Wang et al., 2007; Wang et al., 2006; Wang et al., 2005), the stems of B. gymnorrhiza collected from Guangxi Autonomous Region, China were investigated. A 15-membered macrocycle polydisulfide, gymnorrhizol (3)(Sun and Guo, 2004; Sun et al., 2004), possessing an unprecedented novel carbon skele- ton, was isolated and characterized from the title plant. Interest- ingly, 3 exhibited potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). The latter is an enzyme involved in regulation of insulin signaling and is regarded as a key target for treatment of Type-II diabetes and obesity (Klaman et al., 2000; Elchebly et al., 1999). Its IC 50 value of 14.9 lM stimulated our interest to perform a more-in-depth pharmacological evaluation on this molecule. Unfortunately, the limited amounts of 3 from the Guangxi collection prevented us from further biological inves- tigation. In order to obtain sufficient amounts of 3, we collected the same plants from Guangdong and Hainan Provinces of China and investigated them chemically. In the course of this study, a series of disulfides or polydisulfides were isolated from the collections 0031-9422/$ - see front matter Ó 2009 Published by Elsevier Ltd. doi:10.1016/j.phytochem.2009.06.014 * Corresponding authors. Tel.: +86 20 84114373; fax: +86 20 84115665 (M.-L. Dong), tel./fax: +86 21 50805813 (Y.-W. Guo). E-mail addresses: ls89@zsu.edu.cn (M.-L. Dong), ywguo@mail.shcnc.ac.cn (Y.-W. Guo). Phytochemistry xxx (2009) xxx–xxx Contents lists available at ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem ARTICLE IN PRESS Please cite this article in press as: Huang, X.-Y., et al. Diastereoisomeric macrocyclic polydisulfides from the mangrove Bruguiera gymnorrhiza. Phytochem- istry (2009), doi:10.1016/j.phytochem.2009.06.014