Absolute Configuration and Anticancer Activity of Taxiresinol and Related Lignans of Taxus wallichiana Sunil K. Chattopadhyay, a, * T. R. Santha Kumar, a Prakas R. Maulik, b Sachin Srivastava, a Ankur Garg, a Ashoke Sharon, b Arvind S. Negi a and Suman Preet S. Khanuja a a Central Institute of Medicinal and Aromatic Plants (CIMAP), PO CIMAP, Lucknow-226 015, India b Central Drug Research Institute, Chattar Manzil Palace, Lucknow-226 001, India Received 11 July 2003; accepted 6 September 2003 Abstract—Absolute configuration of taxiresinol 1, a lignan from the heartwood of Taxus wallichiana has been determined as 8R, 8 0 R, and 7 0 R with the help of chemical correlation method and X-ray crystallography. The anticancer activity of taxiresinol 1 and other two lignans 2, 3 were also studied. Taxiresinol 1 showed notable anticancer activity in the in vitro bioassays against colon, liver, ovarian and breast cancer cell lines. # 2003 Elsevier Ltd. All rights reserved. Introduction The Himalayan yew (Taxus wallichiana Zucc.) is a high value tree species that naturally grows on either side of Himalayas. In contrast to the European yew (Taxus baccata L), the Himalayan yew, T. wallichiana has a remarkable history of medicinal use and is also used as a coloring matter and as incense. 1 As a part of our systematic studies on the chemical constituents of the different parts of T. wallichiana, we have isolated and identified several taxoids of different structural types and five of them were new molecules. 2 6 Though the main thrust of phytochemical work on T. wallichiana has been concentrated mainly on the isola- tion and identification of various taxoids, there has not been much work reported on the non-taxoids con- stituent of the plant in comparison to its taxoid con- stituents. In continuation of our studies on the isolation of anti- cancer compounds from the plant T. wallichiana, anti- cancer activity has been detected for three lignans, which have been isolated from the heartwood of the plant. The three lignans have been characterized as taxiresinol 1, isotaxiresinol 2 and ()-secoisolariciresinol 3 on the basis of their spectral characteristics. 7 Recently, we have done a crystal structure of ()-secoisolariciresinol and its absolute stereochemistry has been confirmed as 8R, 8 0 R as previously determined by chemical correlation method. 8 Taxiresinol 1 was previously isolated from the heart- wood of T. wallichiana and its structure was established by Mujumdar et al. in 1972 with the help of low-reso- lution NMR. 7 However, the orientation of the vanillyl and the catechol moiety with respect to the tetra- hydrofuran ring has not been established conclusively, and no 2D NMR data is available for the compound. Most importantly, the absolute stereochemistry of taxi- resinol 1 has not yet been established. In this paper, we would like to report the absolute con- figuration of taxiresinol 1, which has been established with the help of chemical correlation methods and X-ray crystallography. Furthermore, the anticancer properties of taxiresinol 1 and two other lignans, ()- secoisolariciresinol 3 and isotaxiresinol 2 are also reported for the first time for the above molecules. Results and Discussion Taxiresinol 1 was isolated from the ethyl acetate soluble fraction of the methanol extract of the heartwood of T. wallichiana. The molecular formula of C 19 H 22 O 6 for the 0968-0896/$ - see front matter # 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.bmc.2003.09.010 Bioorganic & Medicinal Chemistry 11 (2003) 4945–4948 *Corresponding author. Tel.: +91-522-271-7529; fax: +91-522-234- 2666; e-mail: chattsk@yahoo.com