New 2(3→20)Abeotaxane and 3,11-Cyclotaxane from Needles ofTaxus cuspidata

Abstract

Two new taxoid metabolites, 2; 7; 10-triacetoxy-5,13-dihydroxy-2(3 ! 20)abeotaxa-4(20),11-dien-9-one (1) and 2-acetoxy-5-cinnamoyloxy-9,10-dihydroxy-3,11-cyclotax-4(20)-en-13-one (2), were isolated from the methanol extract of needles of the Japanese yew, Taxus cuspidata.Key words: Taxus cuspidata; Taxaceae; needles; 2(3 ! 20)abeotaxane; 3,11-cyclotaxane Yew trees are a rich source of biologically active taxane diterpenoids such as taxol Ò (paclitaxel), one of the most important drugs for ovarian and breast cancer currently on the market.1,2) Its unique mechanism of action, limited solubility and shortage have generated worldwide interest, and extensive chemical studies have been carried out.1-4) In a continuation of our studies on taxanes, 5,6) two new compounds were isolated from needles of the Japanese yew, Taxus cuspidata.Compound 1 was isolated from a methanolic extract of needles of Taxus cuspidata as white powder {½ D 22 ¼ À40 (c 0.06, CHCl 3 )} and its HR-FABMS analysis revealed the molecular formula as C 26 H 36 O 9 (m=z 531.1998 [MþK] þ , calcd. for C 26 H 36 O 9 K requires 531.1996). A combined analysis by 1-D and 2-D NMR (Table 1) revealed that 1 had a 2(3 ! 20)abeotaxane skeleton 3,5-10) with one keto, two hydroxy and three acetoxy groups. The positions of these functionalities was established by the HMBC spectrum. The relative configuration and proposed conformation of 1 were estimated from the results of an NOESY experiment (Table 1 and Fig. 1), enabling compound 1 to be unambiguously characterized as 2; 7; 10-triacetoxy-5,13-dihydroxy-2(3 ! 20)abeotaxa-4(20),11-dien-9-one. This was the 2-O-acetyl derivative of the compound previously isolated by us from the Chinese yew, Taxus mairei. 10)Compound 2 was isolated as a colorless gummy substance {½ D 22 ¼ þ19 (c 0.11, CHCl 3 )}. Its quasimolecular ion at m=z 561.2256 (MþK) þ generated by HR-FABMS revealed that the molecular formula of 2 was putatively C 31 H 38 O 7 (calcd. for C 31 H 38 O 7 K requires 561.2255). The 1 H-and 13 C-NMR, COSY and HMBC spectra tabulated in Table 2 indicated compound 2 to have a 3,11-cyclotaxane skeleton 3,6,11) with one acetoxy, one cinnamoyloxy, one keto and two hydroxy groups. The HMBC spectrum showed that the acetoxy and the cinnamoyloxy groups were respectively located at the 2-and 5-positions. The relative configuration was determined by an NOESY experiment, and the conformation is proposed to be that shown in Fig. 1. The structure of 2 was characterized as 2-acetoxy-5-cinnamoyloxy-9,10-dihydroxy-3,11-cyclotax-4(20)-en-13-one. This is the 10-O-deacetyl derivative of taxane isolated from seeds of the Chinese yew, Taxus yunnanensis. Biosci. Biotechnol. Biochem., 68 (7), [1584][1585][1586][1587] 2004 Note preparative column (22 Â 500 mm). Plant material. Needles of Taxus cuspidata, which were identified by Prof. Takashi Oritani of Toyama Prefectural University (Japan), were collected in the autumn of 2000 at Tsutsuzigaoka Park (Sendai, Japan).Extraction and isolation. Air-dried needles of Taxus cuspidata were ground...

Diterpenoids

“…132 Taxanes with amino acid side chains at C-5 have been obtained from T. canadensis. 133 Some further taxanes containing an oxetane ring have been isolated 134 from T. chinensis, whilst the rearrangement product 83 was obtained 135 from needles of T. cuspidata.…”

Taxusecone, a Novel Taxane with an Unprecedented 11,12-Secotaxane Skeleton, fromTaxus cuspidataNeedles

“…[6][7][8] of H-5 and H 3 -19. The extensive molecular modeling studies of 1 not only supported the relative conformation, but also explained the anomalous spectral features of H-1.…”

A Novel Taxane 13-Glucoside and Other Taxanes from the Leaves ofTaxus cuspidata

“…T. cuspidata is one of the most extensively investigated yews, and more than 120 taxanes have been isolated from it [1][2][3][4][5][6]. As a continuation of our research on plants from the Taxus genus, we reinvestigated the leaves of T. cuspidata collected at Sendai, Japan [7][8][9][10][11][12][13][14][15], and isolated three new taxanes (l " Fig. 1 [10,11,16]).…”

“…The structure of 1 was concluded to be 2α,9α,10β-triacetoxy-13α-(β-D-glucopyranosyloxy)taxa-4(20),11-dien-5α-ol, the first example of a taxane with 13-glycosidic linkage [18]. [9] was subjected to preparative TLC and HPLC using the same conditions as above to afford compound 1 (2.0 mg, t R = 15.4 min). a Multiplicity: s, singlet; d, doublet; dd, doublet of doublets; m, multiplet; br., broad; o., overlapped.…”