An aliphatic δ-lactone from Hyptis urticoides

An aliphatic δ-lactone from Hyptis urticoides

Phytochemistry, Vol. 30, No. 7, pp. 2417-2418, 1991 Printedin Great Britain. AN ALIPHATIC 0 &LACTONE ALFONSO ROMO 0031-9422/91 %3.00+0.00 1991 Pe...

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Phytochemistry, Vol. 30, No. 7, pp. 2417-2418, 1991 Printedin Great Britain.

AN ALIPHATIC

0

&LACTONE

ALFONSO ROMO

0031-9422/91 %3.00+0.00 1991 PergamonPressplc

FROM HYPTZS URTICOIDES*

DE WVAR, PATRICIA VIDALES and

ANA-LIDIA

PEREZ

Instituto de Quimica, Universidad National Autonoma de Mexico, Circuito Exterior, Ciudad Universitaria, Coyoacan, 04510, Mexico, D.F. (Received 22 October 1990) Key Word Index---Hyptis urticoides; Labiatae; triterpene acid; flavone; a$-unsaturated-&lactone.

Abstract-The new b-lactone hypurticin has been isolated from Hyptis urticoides as its main secondary metabolite. The flavone salvigenin and the triterpenoid ursolic acid were also isolated. The structure of hypurticin was established mainly on spectroscopic grounds.

INTRODUCTION

?A”

Although the genus Hyptis is very large [l] and the majority of its species have shown interesting biological properties [2, 31, relatively few species have been examined chemically. Most of the Hyptis species already studied contain B-lactones of the highly substituted x,/Iunsaturated dodecanoic acid [4-71. The isolation of the new lactone hypurticin (1) and some known compounds from the Mexican plant Hyptis urticoides is reported.

PAc

OAc

1

RESULTSAND DISCUSSION When the aerial parts of Hyptis urticoides were extracted successively with hexane and ethanol, the alcoholic extract yielded the new 8-lactone hypurticin (1) as an oil and ursolic acid, which was identified by direct comparison with an authentic sample. A better yield of hypurticin (0.45%) was obtained when the plant was extracted directly with ethanol and the extract treated with lead acetate. This procedure also afforded ursolic acid and salvigenin (5hydroxy-6,7,4’-trimethoxytlavone) identified by comparison of its spectroscopic data with those reported in the literature [8]. Hypurticin (1) showed IR bands at 1735 and 1635 cn- ’ due to an u&unsaturated-6-lactone as that present in hyptolide [7-j. Its CI mass spectrum showed the molecular ion at m/z 427 (C2,,H2606) and important peaks at m/z 367, 307,247 and 187 which correspond to the successive loss of 60 units, thus indicating the presence of four acetoxy groups. These functions were corroborated by the signals observed in ‘H and 13C NMR spectra (see Experimental). The conjugated double bond of the 6lactone was shown clearly in the ‘H NMR spectrum by the chemical shifts of H-2 (66.24, d, J = 9.8 Hz) and H-3 (6 6.98, dd, J = 9.8, 5.6 Hz). An acetoxy group is attached to C-4 as its gem hydrogen is shown at 6 5.32 as a double doublet signal (.I = 5.6,2.93 Hz). The coupling constant of H-4 with H-3 (5.6 Hz) is indicative of its tl quasi-equatorial configuration [4]. Therefore the side chain at C-5 is

*Contribution No. 1048 from the Institute de Quimica, U.N. A.M.

B quasi-equatorial as indicated by the coupling constant of 2.93 Hz between H-4 and H-5. The absolute stereochemistry of the lactone ring was established by chiroptical measurements. The CD curve showed a positive Cotton effect at 267 nm similar to those obtained for olguine [4] and hyptolide [7], therefore, in hypurticin both C-4 and C-5 have the S-configuration. Hypurticin contains in its side chain a disubstituted double-bond with Z configuration as indicated by the coupling constant of 10.98 Hz shown by the vinylic hydrogens. This unsaturation is localized between C-6 and C-7 since decoupling and COSY experiments have revealed that H-5 is coupled to both H-6 (8.3 Hz) and H-7 (0.98 Hz). These experiments have also shown the presence of acetoxy groups at C-8, C-9 and C-l 1 and that C10 is present as a methylene. The terminal methyl group of the side chain appeared as a doublet (6 1.22, J = 6.6 Hz) due to the interaction with a methyne (64.97, m) which bears an acetoxy function. The above discussion lead us to establish structure 1 for hypurticin. EXPERIMENTAL

Plant material. Hyptis urticoides H.B.K. was collected in Tierra Blanca, Veracruz, Mexico, in July, 1987 (A voucher specimen is deposited in the Herbarium of Colegio de Postgraduados, Chapingo, Mexico). Extraction and separation. Air-dried parts linely ground (1.87 kg) were extracted with hexane and EtOH. The hexane extract (36.4g) chromatographed in silica gel afforded non-polar compounds which did not receive further attention. The alcoholic extract (100.6g) was chromatographed over silica gel and

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Short Reports

eluted with hexane and hexane-EtOAc gradient. HexaneEtOAc-(7:3) fractions gave 2.25 g of ursolic acid. The mother liquors after successive chromatographies yielded 1.3 g ursolic acid and 960 mg hypurticin (1). Air-dried parts of Hyptis urticoides (1.75 kg) were extracted with EtOH. Lead acetate was added to the alcoholic soln and worked-up in the usual manner [9]. CH,CI, residue (16.7 g) was chromatographed in silica gel using as eluent hexane and hexane-EtOAc gradient. Hexane-EtOAc (4: 1) fractions yielded 70 mg ursolic acid and 55 mg salvigenin. Hexane-EtOAc (7: 3-l : 1) frs were combined and purified by successive chromatographies to give 8g hypurticin (1). The ursolic acid was identified by comparison with an authentic sample. The spectroscopic data of the llavone salvigenin were identical to those reported in the literature [8]. Hypurticin (1). [@lo+ 175” (MeGH; c 0.2). UV I~$“‘nm (logs): 204 (4.234). IR v~:i’cn-‘: 1735, 1635. CIMS (CH,) 200 eV, m/z (rel. int.): 427 [M + 11’ (7.5), 367 [427-HOAc]’ (IOO), 307 [367-HOAc]+ (17.3), 247 [307-HOAc]+ (lo), 187 [247-HOAc]+ (19.5), 181 [C,H,O,]+ (13.7), 121 Cl81 - HOAc] + (7.5). EIMS 70 eV, m/z (rel. int.): 43 [C,H,O]+ (100). CD AQ,,~+ 15.56, A~~,~+24.4, AsZ4,+0.48, As,,, + 1.24, Ae2s5 f0.38 (MeOH; c 0.027). ‘H NMR (300 MHz, CDCl,): 66.24 (lH,d,J,,,=9.8 Hz, H-2), 6.98(1H,dd,J,,,=9.8, J,.,=5.6Hz, H-3), 5.32(1H, dd, 5,,,=5.6, J,,,=2.93 Hz, H-4), 5.5O(lH, ddd, J,,,=2.93, J,.,=8.3, 5,.,=0-.98Hz, H-5), 5.79 (lH, dd, J,,, =8.3, J,.,=10.98 Hz, H-6), 5.61 (lH, ddd, 55,7=0.98, .I,,, =10.98, J,,,=9.52Hz, H-7), 5.47 (lH, dd, J,.,=9.52, J,,, =6.1 Hz, H-8), 4.98 (lH, m, H-9), 2.0 (lH, ddd, 5=14.4, 8.5, 6.0 Hz, H-lOa), 1.86 (lH, ddd, J= 14.4, 7.0, 3.17 Hz, H-lob), 4.97 (lH,m, H-11), 1.22(3H,d,.l=6.6 Hz,H-12),2.09(3H,s,Ac),2.08 (3H, s, AC), 2.042 (3H, s, AC), 2.039 (3H, s, AC). ‘%NMR (75.43 MHz, CD&): 6 162.07 (s, C-l), 124.84 (d, C-2), 140.20 (d, C-3), 63.71 (d, C-4), 74.77 (d, C-5), 132.16 (d, C-6), 127.0 (d, C-7),

66.67 (d, C-8), 71.04 (d, C-9), 34.95 (t, C-10) 70.52 (d, C-l 1). 14.68 (t, C-12), 170.50, 170.24, 169.76, 169.72(s, AC), 21.02,20.99,20.96, 20.47 (q, AC). Acknowledgements- -We are indebted to Dr C. Rodriguez and J. Garcia of Colegio de Postgraduados, Chapingo, for collection and identification of the plant material. We also thank Dr Andrts Hernandez Arana of the Universidad Autonoma Metropolitana for the CD analysis and to the chemists, Misael Valentino Torres, Ma. de1 Rocio Patifio, Luis Velasco, Josefina Espifieira, Ruben Gavifio and Jorge Cardenas for technical assistance. This work was supported in part by IOCD-CONACyT project (PVT/AI/NAL/8613662).

REFERENCES

1. Epling, C. (1949) Rev. Museo Plata 7, 153. 2. Sheth, K., Jolad, S., Wiedhopf, R. and Cole, J. R. (1972) J. Pharm. Sci. 61, 1819. 3. Saluja, A. K. and Santini, D. D. (1981) Indian Drugs 19, 127. 4. Alemany, A., Fayos, J. and Martinez-Ripoll, M. (1979) Tetrahedron Letters 3579. 5. Alemany, A., Marquez, C., Pascual, C., Valverde, S., Martinez-Ripoll, M., Fayos, J. and Perales, A. (1979) Tetrahedron Letters 3583. 6. Delgado, G., Romo de Vivar, A. and Pereda-Miranda, R., (1985) Heterocycles 23, 1869. 7. Achmad, S., Hoyer, T., Kjaer, A., Makmur, L. and Norrestam, R. (1987) Acta Chem. Stand. B41, 599. 8. Wollenweber, E. and Wassum, M. (1972) Tetrahedron Letters 797. 9. Mabry, T. J., Miller, H. E., Kagan, H. B. and Renold. W. (1966) Tetrahedron 22, 1139.