ORGANIC LETTERS
A 9-Hydroxyiridoid Isolated from Junellia seriphioides (Verbenaceae)
2000 Vol. 2, No. 5 699-700
Henrik Franzyk,† Søren Rosendal Jensen,*,† Carl Erik Olsen,‡ and Juan Marcelo Quiroga§ Department of Organic Chemistry, The Technical UniVersity of Denmark, DK-2800, Lyngby, Denmark, Department of Chemistry, The Royal Danish Agricultural and Veterinary UniVersity, DK-1871 Frederiksberg C, Denmark, and Centro Nacional Patago´ nico, CONICET, 9120 Puerto Madryn, Chubut, Argentina
[email protected] Received January 14, 2000
ABSTRACT
An unusual iridoid glucoside, namely 9-hydroxy-8-epihastatoside (1), was isolated from Junellia seriphioides (Verbenaceae), together with the known compounds auroside (2), pulchelloside I (3), and 8-epihastatoside (4) as well as verbascoside.
Junellia seriphioides (Gillies & Hook.) Moldenke (Verbenaceae) belongs to the dryland vegetation in Northern Patagonia; it has been used in traditional medicine by Tehuelches Amerindians since pre-Hispanic times. Previous chemical work on this genus comprises only an investigation of the nectar composition.1 We have now studied the polar constituents of the plant. The water-soluble part of the ethanolic extract was submitted to reverse phase chromatography with H2OMeOH mixtures as eluents. This gave four iridoid glucosides (1-4) as well as verbascoside. Compounds 2-4 were identified as auroside,2 pulchelloside I,3 and 8-epihastatoside,4 respectively, by comparison with published NMR data. Compound 1 was obtained as a glass [R]21D ) -246° (c 0.5; MeOH) and the FAB MS of m/z 443 [M + Na]+ corresponded to the formula C17H24O12. The 13C NMR spectrum showed 17 peaks of which 6 could be assigned to a β-glucopyranosyl moiety. The chemical shifts of the †
Technical University of Denmark. The Royal Danish Agricultural and Veterinary University. § Centro Nacional Patago ´ nico, Argentina. (1) Bernadello, G.; Galetto, L.; Forcone, A. Biochem. Syst. Ecol. 1999, 27, 779. (2) Junior, P. Planta Med. 1985, 51, 229. (3) Bianco, A.; Caciola, P.; Guiso, M.; Iavarone, C.; Trogoli, C. Gazz. Chim. Ital. 1981, 201. (4) Foderato, T. A.; Stermitz, F. R. Phytochemistry 1992, 31, 4191. ‡
10.1021/ol0055521 CCC: $19.00 Published on Web 02/04/2000
© 2000 American Chemical Society
remaining 11 peaks indicated an iridoid aglucone, and the presence of a carbonyl signal (δ 214.3) suggested a structure similar to that of 8-epihastatoside (4) also present in the plant. Comparison with the spectrum of this showed a good overall similarity, except that 1 contained a hydroxyl-bearing, quaternary carbon atom not seen in 4. The 1H NMR spectrum showed the presence of a proton at C-8 in 1 since the 10CH3 peak appeared as a doublet (J ) 7 Hz), and the remaining part was also otherwise very similar to that of 4. This left us with the only possibility of assigning the quaternary hydroxyl-bearing carbon atom as C-9, thus leading to the structure 1 for the new compound. HSQC and HMBC spectra allowed assignment of all signals in the NMR spectra (Table 1). In particular, the HMBC spectrum proved the low-field position of C-9 since a strong three-bond interaction was seen between the signal at δ 75.8 and that of the 10-methyl group.
Table 1. 13C NMR (75 MHz) and 1H NMR (500 MHz) Data for 1 and the Model Compounds 4 and 5 1 atom
δC
1 3 4 5 6 7a
96.6 157.5 107.5 75.4 214.3 39.5
7b 8 9 10 11 Me 1′ 2′ 3′ 4′ 5′ 6′
36.2 75.8 17.7 168.0 53.1 100.5 73.4 76.4 70.6 77.3 61.5
4
5
δH
δH
δH
5.70, s 7.72, s
5.95, s 7.75, s
2.56, dd (17.6, 9.6) 2.25, dd (17.6, 7.0) 2.39, m
1.13, d(7.2) 3.66, s 4.73, d(8) 3.29, dd 3.46, t 3.37, t 3.44, m 3.86, dd 3.69, dd
2.50, dd (18.3, 8.6) 2.23, dd (18.3, 6.9) 2.62, m 2.72, d (10.3) 1.01, d(6.9) 3.65, s 4.75, d(8) 3.24, dd 3.46, t 3.35, t 3.45, m 3.89, dd 3.67, dd
5.92, d(1.5) 7.74, s
2.74, dd (18.4, 9.3) 1.93, dd (18.4, 8.4) 1.97, m 2.23, dd (10.2, 1.5) 1.11, d(6.4) 3.64, s 476, d(8) 3.25, dd 3.45, t 3.36, t 3.46, m 3.87, dd 3.68, dd
Assuming the usual iridoid glucoside configuration at C-1, C-5, and C-9, only the stereochemistry at C-8 remained to be determined. The co-occurrence of 1 with 2-4 in the plant, and the possibility of 4 being the immediate precursor of 1, suggested the 8R-configuration shown. However, in a few cases members of both epimeric series can be present in the same plant as seen in some Penstemon species4 and also in Verbena,5 a genus closely related to Junellia. Consequently, we had to solve this problem. It has earlier been shown that an NOE between H-8 and H-1 cannot be used as proof of the configuration at C-8 due to conformational shifts in the cyclopentane ring when going from one epimer to the other.6,7 The chemical shift of C-9 is in many iridoid (5) Miltz, S.; Rimpler, H. Z. Naturforsch. 1979, 34c, 319. (6) Franzyk, H.; Jensen, S. R.; Stermitz, F. R. Phytochemistry 1998, 49, 2025.
700
glucosides indicative of the stereochemistry at C-8,8 but this is limited to compounds where both these carbon atoms carry a proton, which was not the case here. Also, direct comparison of the 13C NMR spectrum of 1 with those5,7 of 4 and its 8-epimer, hastatoside (5), was not conclusive due to lack of similar model compounds. The 1H NMR data proved more useful. In both 4 and 5 the coupling constant J8,9 has a large value (ca. 10 Hz, Table 1), demanding the dihedral angle ∠8,9 to be either ca. 180° or ca. 0.° Molecular models showed that a conformational change in the cyclopentane ring was necessary to obtain such angles when going from 4 to 5. Thus, an 8E-like conformation was necessary in the former and an E8-like conformation in the latter, respectively. This would allow both conformers to have a pseudoequatorial methyl group and a pseudoaxial proton at C-8, consistent with the measured coupling constants. The J7,8 coupling constants measured for 1 (Table 1) were very similar to those seen for both 4 and 5. Therefore, 1 presumably assumes a conformation similar to one of them. Upon comparison of the shift values from the two protons at C-7 in the spectrum of 1 (δ 2.56 and 2.25) with those of 4 (δ 2.50 and 2.23), they were found to be almost identical. Conversely, the corresponding values for 5 (δ 2.74 and 1.91) differed considerably. Consequently, we conclude that the new compound is 9-hydroxy-8-epihastatoside. 9-Hydroxy-substituted iridoid glucosides are very rare. So far, a few have been reported from Gelsemium,9 but these are all atypical with the glucosyl moiety at either the 3- or at the 7-position. Thus 1 is the first ordinary iridoid glucoside with a 9-substituent among the more than 1000 different compounds so far published. Acknowledgment. We thank Dr. Alejandro Bisigato, Centro Nacional Patago´nico, for identifying the plant material. Supporting Information Available: Experimental details. This material is available free of charge via the Internet at http://pubs.acs.org. OL0055521 (7) Franzyk, H.; Jensen, S. R.; Thale, Z.; Olsen, C. E. J. Nat. Prod. 1999, 62, 275. (8) Damtoft, S.; Jensen, S. R.; Nielsen, B. J. Phytochemistry 1981, 20, 2717. (9) Jensen, S. R.; Kirk, O.; Nielsen, B. J. Phytochemistry 1987, 26, 1725.
Org. Lett., Vol. 2, No. 5, 2000
