Iridoid glycosides of additional Penstemon species

Pergamon

0031-9422(94)00470-6

IRIDOID GLYCOSIDES

OF ADDITIONAL

Phytochemmry. Vol. 37, No. 5, pp. 1283-1286, 1994 Copyright 8 1994 Elsenn Sciena Ltd Prialed in Great Britain. All righls resewed CO31-9422,94 57 00 + 0.00

PENSTEMON

SPECIES*

FRANK R. STERMITZ,ANDREI BLOKHIN,CHRISTINAS. POLEY and ROBERTE. KRULL Department of Chemistry, Colorado State University, Fort Collins, CO 80523, U.S.A. (Received 20 Apri/ 1994)

Key Word Index-fenstemon

barrettiae, P. glaber, P. parryi; Scrophulatiaceae;

iridoid glycosides.

Abstract-Previously undescribed iridoid glycosides were isolated from Penstemon species as follows: P. parryi: 8epitecomoside or 7b-hydroxyplantarenaloside, 2’-O-coumaroyl-8-epitecomoside and 2’-O-coumaroylplantarenaloside, and P. barrettiae: 2’-0-foliamenthoylplantarenaloside. Detailed high field NMR assignments were made for durantoside-I which was isolated from P. glaber.

INTRODUCTION

Novel iridoid and other glycosides continue to be reported from species of the American wildflower genus Penstemon [ 1, 23. We report here the iridoid glycoside content of several species from the western U.S.A. RESULTS AND DISCUSSION

Penstemon parryi (Gray) Gray belongs to subsection Centranthifolii of section Peltanthera, subgenus Penstemon [3]. The content of iridoid glycosides from none of the 29 species in the section have as yet been reported. In the U.S.A., P. parryi is apparently restricted to the lower deserts of the southwest. Above ground plant parts yielded the common iridoids catalpol and plantarenaloside and the previously undescribed iridoids 8epitecomoside or 7-fi-hydroxyplantarenaloside (l), 2’-O-coumaroyl-8-epitecomoside (2) and 2’-O-coumaroylplantarenaloside (3). Only trace amounts of catalpol, 2, and 3 were found so the species is dominated by plantarenaloside and 1, a novel pattern among penstemons so far studied. P. barrettiae Gray is in subgenus Dasanthera, from which P. cardwellii [4], P. newberryi [S] and P.fruticosus [6] have previously been studied. P. barrettiae is a rupiculous endemic in the Columbia river gorge area of the northwest U.S.A. It is extremely rare in nature, but has been propagated for planting along Interstate 84 in Oregon. Leaves of P. barrettiae were found to contain aucubin, catalpol, geniposidic acid, plantarenaloside (the major iridoid) and the previously unreported 2’-foliamenthoylplantarenaloside (4). The acetophenone glycoside picein was also found. For comparison, P. cardwellii had been reported [4] to contain mussaenoside and bartsio-

*Chemistry of the Scrophulariaceae, Part 31. Part 30: Stermitz, F. R., Abdel-Kader, M. S., Foderaro, T. A. and Pomeroy, M. (1994)Phytochemistry.37, 997.

side, P. newberryi was reported [S] to contain catalpol (the major iridoid), I-epiloganin, mussaenoside, gardoside methyl ester and lO-bisfoliamenthoylcatalpol, along with p&in and verbascoside, while P. fiuticosus had aucubin, eurostoside (IO-p-coumaroylacubin), mussaenoside and Z’cinnamoylmussaenoside [6]. In terms of iridoid glycoside content at least, these four species of subgenus Dasanthera are therefore quite distinct chemically. P. glaber Pursh. is in section Habroanthus (=Glabri), along with several other widespread blue-flowered penstemon species of the Rocky Mountains. Several of these have at one time or other been designated as varieties of P. glaber. Leaf material of a sample from the northernmost range of the species yield catalpol, globularin and lamiide as major iridoids, along with a small amount of durantoside-I, 5, previously known from Duranta repens (Verbenaceae) [7]. Since complete high field NMR data were not previously published for 5, these are given in Table 1. The relatively uncommon iridoids globularin and lamiide were also reported [8] from P. strictus, a close relative of P. glaber, also from section Habroanthus. Compound 4 tested negative for activity against a variety of gram positive, gram negative and yeast organisms as well as Mycobacterium smegmatis and M. fortuitum. 8-Epitecomoside (7-fl-hydroxyplantarenaloside) (1) and its derivatives 2 and 3

The major component, [all5 - 122 (MeOH; c 1.34), from P. parryi had M, 376 by electrospray MS. The presence of 16 carbons in the ‘%NMR spectrum and analysis of the ‘H NMR spectrum (Table 1) suggested the molecular formula Ci6H,,0io which would be that of tecomoside [9-l 11. The spectral data were close to, but not identical with, those reported for tecomoside, although DEPT ’ 3C NMR spectra revealed the same number of methyl, methylene and methine carbons as in

1283

F. R.

1284

STFRMITZ

et al.

R2

R = OH = coumaroyl R = H = cinnamoyl

R’

1 2

Glucosyl 2-O-coumaroyl

R2

R3

R4

Cl10

OH

H

Cl10

OH

H

Cl-10

H

II

CIfO

H

H

glUCOSyl

3

2-O-coumaroyl glucosyl

4

2- O-foliamenlhoyl

5

Glucosyl

foliamelhoyl

glucosyl COOMc

0-cinnamoyl

tecomoside. NMR differences were mainly confined to the C-6 to C-9 portion of the molecule, which suggested stereochemical changes at C-7 and/or C-8 when compared with tecomoside. Interestingly, a ’ 3C NMR spectrum had been calculated for the then unknown 1 [ll] (Table 1) and used as partial evidence for a revision in the original proposed structure for tecomoside. The pertinent resonances for 1 were remarkably close to those calculated [I I]. In particular, the C-9 resonance (651) was described as diagnostic for an r rather than /I C-8 methyl. A simulated “CNMR spectrum [8] for 5hydroxy-8epiloganin, which bears a carbomethoxy instead of an aldehyde group at C-4, was also similar to that of 1. Although these data and the calculated spectra closely matched those expected for 1, a corresponding structure with a C-7a-OH remained a possibility since such a structure was not available for comparison. Irradiation of the C-10 methyl hydrogens at 60.92 resulted in a large enhancement of the H-7 proton resonance at 63.45 which confirmed that the methyl and H-7 were on the same side of the ring. This assured the structure as 1 and confirmed the empirical 13C calculations [8, 1 I]. A minor component of P. parryi had M, 522 according to electrospray MS and had ‘% and ‘HNMR spectra (Table 1) which corresponded to those of 1 with the addition of an acylating coumaroyl group. The ‘H NMR resonances for H-7 and H-6’were not shifted significantly from those in 1. A new resonance ofd4.66 was present and could be assigned to a downlield shifted proton on the sugar portion of the molecule. A decoupling experiment showed this resonance to be coupled to the anomeric H on the sugar, thus placing the coumaroyl group at C-2’ and resulting in structure 2. Another minor component, 3, had M, 506 from electrospray MS, which indicated one 0 atom less than 2 and the NMR spectra (Table 1) confirmed the general relationships between 2 and 3. In the i3CNMR spectra a chief difference was the replacement of the C-7 677 resonance for 2 by one at 632.9, which suggested that 3

OH

lacked an oxygen at C-7 and hence was 2’-O-coumaroylplantarenaloside. This was confirmed by comparison of the spectra with those of plantarenaloside, isolated from the same plant, as well as a decoupling experiment which placed the coumaroyl group at the C-2’ sugar OH as for 2.

2’-0-Foliamenthoylplantarenaloside

(4).

The 13C and ‘HNMR spectra (Table 1) of 4, [z]:: - 70.1 (MeOH; c 1.06), isolated from P. barrettine, were essentially those for plantarenaloside in terms of resonances for the iridoid aglycone portion of the molecule. Similarly, one could account for a foliamenthoyl group by comparison with literature data for other iridoids, such as nemoroside [12, 131. which contain such a functionality. A 64.64 quartet ‘H resonance for a proton on a carbon bearing an acylated oxygen was present and this resonance was shown to be coupled to the anomeric sugar proton at 64.72. These data confirmed the structure as 4.

EXPERIMENTAL

Plunt sources. Plants were identified by Prof. D. M. Wilken, Department of Biology, Colorado State University and vouchers (with FRS Nos as below) were deposited in the Colorado State University Herbarium. Collections were as follows: P. parryi (FRS 3 15), 14 March 1987, Pima Co., Arizona, I mile west of Quijotoa along SH 86; P. horrettiae (FRS 445), 28 April 1992, Hood River Co., Oregon, at the Mosier exit (89) off Interstate 84 east of Hood River, Oregon; P. glaher (FRS 474) I3 June 1993, Fremont Co., Wyoming, US Highway 287 20.5 miles south of SH 28 junction. Isolutions. Dried, ground leaves (24 g) of P. parryi were extracted twice with MeOH for 24 hr. the extracts combined, and coned in uacuo to yield 3.4 g of dry extract. This was partitioned between H,O and Et,0 and the

77.7 43.0 51.1 13.9 192.5 98.8 74.2 77.3 71.5 78.4 62.7

97.4 165.3 122.7 70.7 46.3

78.1 41.7 50.0 13.6

1 3 4 5 6

7 8 9 10 I1 1’ 2 s 4 5’ 6

1.97 dd (7.3, 13.3) 2.53 dd (I 3.3, 5.6) 3.45 m 2.22 nr 2.71 dd (1.1, 10.8) 0.92 d (7.3) 9.20 s 4.56 d (7.9) 3.11-3.36m 3.1 l-3.36 m 3.1 l-3.36 m 3.11 3.36m 3.61 dd (6.1, 12) 3.87 dd (1.8, 12)

5.81 d (1.1) 7.35 s

1

7.37 d (8.6) 6.71 d(8.6) --

6.20 d (16) 7.45 d (16)

1.82 dd (8.6, 2.45 dd (5.6, 3.55-3.60 m 2.lOm 2.66dd(1.3, 0.84 d (4.5) 8.75 s 4.74 d (8.0) 4.65 dd (8.0, 3.21-3.34 m 3.21-3.34 m 3.21 -3.34 m 3.61 dd (6.1, 3.86dd(1.8,

-

5.74 d (1.5) 7.11 s

2

12) 12)

9.3)

11.7)

12.8) 12.8)

C-2”(128.6,

---), C-3”(144.1,6.72

3.30.

169.5 114.7 48.3 127.0 131.6 116.9 161.5

32.9 34.2 52.6 16.6 192.0 98.3 75. I 75.3 71.6 78.5 62.7

97.4 163.3 126.1 73.7 37.2

I. NMR spectral

4.72. 5 at 500 MH.q Ref. CH,OD

169.5 114.4 148.4 126.5 131.5 117.1 162.3

77.8 42.4 51.5 13.9 191.8 98.3 75.1 75.3 71.6 7g.6 62.7

97.1 163.4 126.5 70.5 45.2

Voliamenthoyl Portion (C and corresponding H): C-l”(169.3~). l.75), C-IO” (16.2, 1.60).

Kalculated [I I]. SOverlapping multiples.

lCD,OD. 1-J at 300 MHG 4 at 200 MHz; Ref. HDO

OMe

4”

2” 3 ,,

;i 1I,

co

96.5 164.0 126.4 70.4 46.8

It

CorH

Table

I). C-4”(28.1,

7.43 d (8.5) 6.77 d (8.5)

6.27 d (16) 7.51 d (16) _

P

33.0 34.3 52.5 16.6 191.7 98.0 73.7 75.3 71.7 78.5 62.7

97.1 163.4 126.1 73.7 37.3

“2.2 m), C-5”(39.1,2.13),

1.85 m 2.25 m 0.9, 1.8 m 1.8 m 2.41 hs 0.85 d (6.6) 8.80 s 4.77 d (8.1) 4.70 dd (8.1, 9.2) 3.24-3.38 m 3.24-3.38 m 3.24-3.38 m 3.64 m 3.90 dd (2, 12)

-

5.79 d (0.5) 7.18 s

3

data for iridoid glycosides*

C-6”(138.4,

I

168.1 119.3 146.4 135.9 130.0 129.2 131.5 51.7

80. I 78.4 58.4 21.3 168.0 99.7 74.4 77.5 71.7 78.7 62.8

94.0 152.2 115.7 69.0 45.6

---), C-7”(125.7,5.33),

i.35 hs 0.85 d (6.6) 9.00 s 4.72 d (8) 4.64 dd (8, 9.2) 3.2-3.7 m 3.2-3.7 m 3.2-3.7 m 3.6 m 3.86 dd (2. 12)

$ 0.9, 1.8 m

1.77 m

-

5.76 s 7.18 s

4

C-fj”(59.4,4.03),

7.61 m 7.40 m 7.4Om 3.74 s

C-9”

d (8.0) dd (8.0, 9.2) dd (8.7, 8.8) dd (9.6, 8.8) m dd (11.9, 2.2) dd (11.9, 6.0) 6.61 d (16.1) 7.78 d (16.1)

4.62 3.20 3.39 3.27 3.34 3.89 3.66 -

2.98 s 1.18s

2.34dd (1.6. 16.2) 2.49dd (5.1, 16.2) 4.85 dd (I .6, 5.0)

5.84 d (0.7) 7.45 s

5

(12.5,

1286

F. R. STERMITZ et

H,O evapd to yield 3.0 g of residue which was purified by gradient) with the VLC (Cl* silica gel, H,O/MeOH following results: fr. 2 (5% MeOH), 21.5 mg catalpol after rechromatography; frs 4-5 (15-20% MeOH), 480 mg of essentially pure 1; frs 18-9 (3540% MeOH), 220 mg plantarenaloside; frs lo- 11 (5060% MeOH), 20 mg of plantarenaloside and 18 mg of 2 after rechromatogrpahy; fr. 12 (70% MeOH), 16 mg of 3 after rechromatography. Dried, ground leaves (25 g) of P. barrettiae were extracted as above to yield 8 g of residue. Of this, 5.6 g was purified by VLC as above with the following results: fr. 3, 30 mg of catalpol/aucubin mixt.; fr. 4,214 mg of catalpol, aucubin, geniposidic acid mixt.; fr. 5, 430 mg of mixt. which was about 9: 1 geniposidic acid/picein as shown by rechromatography; frs 7-8, 1.02 g of pure plantarenaloside (frs 6 and 9 yielded an additional 625 mg of less pure plantarenaloside); frs 12- 13, 864 mg of 4. Dried, ground leaves (4.85 g) of P. glaber were extracted as above to yield 1.40 g of residue. This was purified as above with the following results: frs 4-6.73 mg of catalpol; frs 7-10, 111 mg of lamiide; frs 1l-17 (50-80% MeOH). 68 mg of globularin and 13 mg of durantoside-I, 5 after rechromatography. All known iridoids were compared with samples we had previously isolated with the exception of 5. Our NMR spectral data for 5 compared closely with those of the lit. [7] taken at 60 MHz and 5 had the same TLC R, as that of durantoside-I in an iridoid mixt. obtained as a standard.

al.

Acknowledgements-This work was supported by National Science Foundation grant CHE-90235608. We thank H. Rimpler for a sample of durantosides.

REFEREKCEIS

1. Abdel-Kader, M. S. and Stermitz, F. R. (1993) Phytochemistry 34, 1367. 2. Teborg, D. and Junior, P. (1991) Planta Med. 57, 184. 3. Bennett, R. W., Lodewick, K. and Lodewick, R. (1987) Penstemon Nomenclature, pp. 6-14. K. Lodewick, Eugene, OR. 4. Junior, P. (1984) Pfanta Med. 50, 530. 5. Stermitz, F. R., Abdel-Kader, M. S., Foderaro, T. A. and Pomeroy, M. (1994) Phytochemistry 37, 997. 6. Ofterdinger-Daegel, S. and Junior, P. (I 993) Planta Med. (Suppl.) 59, A602. 7. Rimpler, H. and Timm, H. (1974) Z. Naturforsch. 29c, 111. 8. Junior, P. (1985) PIanta Med. 49, 229. 9. Bianco, A., Guiso, M., Iavarone, C., Massa, M. and Trogolo, G. (1982) Gaze. Chim. Ital. 112, 199. 10. Imakura, Y., Kobayashi, S., Kida. K. and Kido, M. (1984) Phytochemistry 23, 2263. 11. Damtoft, S., Jensen, S. R. and Nielsen, B. J. (1981) Phytochemistry 20, 27 17. 12. Junior, P. (1983) Planta Med. 47, 67. 13. Arslanian, R. L.. Anderson, T. and Stermitz, F. R.

(1990) J. Nat. Prod. 53, 1485.