Norcyperone, a Novel Skeleton Norsesquiterpene from Cyperus rotundus L

A novel norsesquiterpene, named norcyperone (1), and three known compounds: (-)-clovane-2,9-diol (2), rosenonolactone (3), and 5α,8α-epidioxy-(20S,22E,24R)-ergosta-6,22-dien-3β-ol (4) were isolated from the rhizomes of Cyperus rotundus L. The structure of 1 was elucidated as 8,11,11-trimethylbicyclo[5.3.1]undecane-5α, 8α-epoxy-3-one on the basis of extensive spectroscopic analyses, including 1D- and 2D-NMR, MS experiments, and single-crystal X-ray diffraction. This is the first report of a 8,11,11-trimethyl- bicyclo[5.3.1]undecane-3-one type norsesquiterpene with a tetrahydrofuran ring at C-5 and C-8.


Introduction
The rhizomes of Cyperus rotundus L. have been used in traditional Chinese medicine as an estrogenic and anti-inflammatory agent for the treatment of women's diseases and also used for treatment of stomach ache and bowel disorders [1]. The extract of the rhizomes of C. rotundus L. showed anti-diabetic activity [2], acetylcholinesterase inhibitory activity [3] and antidiarrhoeal activity [4], as well as inhibition of nitric oxide and superoxide production [5]. Previous phytochemical studies on C. rotundus L. have led to the identification of more than 60 sesquiterpenes with a diversity of skeletons [6,7] besides flavonoids, furochromones, triterpenes and sterols [8,9]. In the course of our phytochemical investigation of this species, a novel norsesquiterpene 1, named norcyperone, together with three known compounds: (-)-clovane-2,9-diol (2), rosenonolactone (3), and 5α,8αepidioxy-(20S, 22E,24R)-ergosta-6,22-dien-3β-ol (4) were isolated from the rhizomes of C. rotundus L. Herein we report the isolation and structural elucidation of these compounds.
The relative stereochemistry of 1 was determined on the basis of a NOESY spectrum. The NOESY correlations between H-1/CH 3 -12, CH 3 -12/ H-7, H-7/CH 3 -14, H-5/H-6a, H-6a/H-7 suggested that all these atoms were in β-orientation (Figure 3), which further confirmed by single-crystal X-ray diffraction ( Figure 4). The crystal structure showed a six-numbered ring A in 'twist boat' conformation, an eight-numbered ring B in 'boat' conformation, and a five-numbered tetrahydrofuran ring C in an 'envelope' conformation, in which rings A and C are cis-fused. Thus, the structure of 1

Conclusions
A novel skeleton norsesquiterpene, norcyperone, together with three known compounds 2-4 were isolated from the rhizomes of C. rotundus L. Although a 8,11,11-trimethylbicyclo[5.3.1]undecane has been reported as a synthetic intermediate derived in the course of synthesis of the taxane-AB-fragment with a spiro-cyclopropyl group [14], this is the first report of a 8,11,11-trimethylbicyclo[5.3.1]undecane-3-one type norsesquiterpene with a tetrahydrofuran ring at C-5 and C-8. Compounds 2-4 were isolated from the genus Cyperus for the first time. These findings enrich our knowledge of the chemical constituents of C. rotundus L.

General
Melting points were determined on Fisher-Johns Melting Point Apparatus and are uncorrected. IR spectra were measured with a Bruker IFS-55 infrared spectrometer (KBr). Optical rotations were recorded on a Perkin-Elmer 241 automatic recording spectropolarimeter. EI mass spectra were recorded on a Zabspec E mass spectrometer. HR-ESI-MS was taken on a LTQ Orbitrap TM Mass spectrometer. Column chromatography was performed over Silica gel (200-300 mesh) (Qingdao Marine Chemical Factory) and Sephadex LH-20 (Pharmacia). Nuclear magnetic resonance (NMR) spectra were measured on a Varian Inova-600 spectrometer operating at 600 MHz ( 1 H) and 150 MHz ( 13 C), respectively.

Plant material
The