I100
Journal of Natural Products Vol. 50, NO.6 , pp. 1100-1 107, NOV-DK1987
HIGHLY UNSATURATED ISOPENTYL AMIDES FROM ACHILLEA WlLHELMSlI HARALDGREGER Institute of Botany, Uniwsity of Vienna, A-1030 Vienna, Austria and OTMARHOFER
Institute of Organic Chemistry, University of Vienna, A - 1 0 9 0 Vienna, Austria ABsTRKT.--The petroleum ether/Et,O extract of the underground parts of Achillea wilbelmsii afforded 13 novel alkamides. Their structures and stereochemistries were determined by spectroscopic methods. The general pattern is characterized by derivatives with highly unsaturated acid moieties with different carbon chain lengths. The C, amides predominate, and smaller amounts of C,4 derivatives are observed. This species is particularly characterized by the accumulation of isopentyl amides that represent a new type of alkamide.
The genus Achillea is characterized chemically by the frequent accumulation of olefinic and acetylenic alkamides, a biogenetic capacity that it shares with some other genera of the Compositae-Anthemideae as well as with members of the CompositaeHeliantheae. Besides the more widespread isobutyl and phenethyl amides, the occurrence of compounds with cyclic amide moieties is confined to the tribe Anthemideae (1). As shown in preceding articles, Achillea species are especially rich in piperidides, pyrrolidides, and the corresponding dehydro derivatives (piperideides, pyrrolideides) (1-4). More recently, a series of hitherto unknown pyrrolides has been isolated from Achillea ageratifolia (Sibth. & Smith) Boiss. (5). Apart from the different amine parts, trends towards different carbon chain lengths and stereochemistries as well as different levels of unsaturation within the acid residues have been shown to serve as additional chemotaxonomic criteria within Achillea ( 1,4,5). As part of a continuing comparative analysis on alkamides within that genus, we have now investigated Achillea wilhelmsii C. Koch (syn: Achillea santolina auct. mult., non L.), originating from Turkey. This is a Irano-Turanian element that is particularly characterized by strongly developed root suckers. In Egypt and in some Mediterranean countries the plant is used for stomach ailments and digestive disorders (6). Previous papers on this species have been concerned with sesquiterpene lactones (7- 10) and plyacetylenes (1 l), whereas a more recent article has described the different essential oil compositions of a Turkish and of an Egyptian provenance (6). The present study on the underground parts reveals a series of 13 new alkamides whose structures were elucidated by spectroscopic methods. RESULTS AND DISCUSSION The polar column fractions (Si gel) of the petroleum ether/Et,O extract afforded alkamides that fall into two groups on the basis of different carbon chain lengths of the acid residues. The C,, amides predominated, and smaller amounts of C14 derivatives were observed. The structure elucidation of the new alkamides was mainly based on 'H nmr (Tables 1 and 2) and mass spectra (see Experimental section). However, apart from the characteristic uv spectra of the highly unsaturated acid residues, special attention was also paid to the very informative ir data (4,18). C,, ALKAMIDESl-7.-Due to the highly unsaturated C,, fatty acid moieties of the acetylenic derivatives, the 'H-nmr spectra were relatively simple and, thus, allowed a straightforward interpretation. In the uv spectra the 2,4-dienamide
Nov-Dec 19871 Greger and Hofer: TABLE 1.
Unsaturated Isopentyl Amides
1101
'H-nmr Data for Compounds 1-Y Compound
Proton No.
1 2-H . 3-H . 4-H 5-H . 6-H . 7-H . 8-H . 9-H . 10-H NH . 1'-H . 2'-H 3'-H . 4'-H . ArylH
. . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2
6.35d 6.72d
6.33d 6.80d -
-
-
-
2.02s 5.48brt 3.37dt 1.44dt 1.61111 0.92 d
-
-
-
-
-
7.17-7.36 m
-
-
-
-
-
5.59dqb 6.24dq 1.95 dd 5 69brc 3 37dr 1.44dt 1.63m 0.92 d
5 74d 7 2Odd 6.14 dd 6.08dt 2.15 dr 1.45m 1.30111 1.30m 0 88t 5.38brt 3.36dt I45dt 1.64m 0.92d
-
-
-
5.60dqb 6.24dq 1.95dd 5.55 brr 3.19dd 1.84m 0.93 d
-
6
5
6.25 d 6.80d
6.33d 6.82d
-
-
4
3
5.59dqb 6.23dq 1.95dd 5.55brt 3.61dt 2.88~
Coupling constants (Hz): Acid moieties: 1.3,4: 2 . 3 ~ 1 5 ;8,9=11; 8,10=1.8; 9.10'7. 3: 5,6=6,7=9,10=7. Amine moieties: 1,2,5: NH,I'= 1',2'=2',3'=3'.4'=7. NH,1'=1',2'=7.
6.29d 6.73d -
-
2.02 s 5.52brt 3.61dt 2.85~
7
-
5.68d 6.10m 6.10111 2 14dr 1.44m 129m 1.29111 0.89 c 5.45brt 3.60dc 2.85 I
-
-
7.18-7.37m
7.17-7.37 m
-
2.6: 2,3=15. 5,7: 2,3=4.5=15; NH,1'=1',2'=2'.3'=7. 4,6,7:
chromophore of 5 and 7 was indicated by a sharp maximum at 25 1 nm; the en-diynenamide and triyn-enamide chromophores of the remaining compounds 1-4and 6 were clearly distinguished by a series of typical maxima (see Experimental). The ir spectra with the >N-H stretching at 3440 cm-' and a strong band at 1500 cm-' (>N-H/CH bend) were indicative for secondary amides. Phenethyl moieties were characterized TABLE2.
'H-nmr Data for Compounds S-13'
~~
Compound
Proton No. 8
9
~
I
~
-10
11
12
13 ~
2-H 3-H 4-H 5-H 6-H 7-H 12-H 13-H 14-H NH 1'-H 2'-H 3'-H 4'-H
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
. . . . . . . . . . . . . .
5.93d 7.32dd 6.48dd 7.05 dd 6.58 dd 5.66d 5.61dqb 6.21dq 1.97dd 5.46 br t 3.36dt 1.44dt 1.63 m 0.93 d
5.91d 7.26dd 6.40dd 6.56dd 6.77dd 5.83 d 5.60dqb 6.19 dq 1.95dd 5.45brt 3.37dt 1.44dt 1.63 m 0.92 d
5.77d 7.19dd 6.18dd 6.06dt 2.39m 2.391-11 2.24~ 0.99t 5.39brt 3.37dt 1.43dt d
0.93 d
5.95 d 7.31dd 6.47 dd 7.05 dd 6.58dd 5.66d 5.60dqb 6.20dq l.98dd 5.52 brt 3.18 dd 1.81 m 0.94d -
5.93d 7.25 dd 6.39 dd 6.56dd 6.76 dd 5.83 d 5.60dqb 6.18 dq 1.95 dd 5.52brt 3.18dd 1.81m 0.94 d
5.78d 7.20dd 6.21dd 6.08dt c
5.50dqb 6.14 dq 1.93 dd 5.43 brt 3.37dt 1.45 dt 1.65 m 0.93 d
"250 MHz, G/ppm, CDCI,/TMS. bbr pseudo d . '2.38-2.50 ppm. dl.50-1.70 pprn. Coupling constants (Hz): Acid moieties: 8,ll: 2,3=4,5=15; 3,4=5,6=6,7=12,13=11; 12,14= 1.8; 14,15=7. 9,12:2,3=4,5=6,7=15; 3,4=5,6=12,13=11; 12,14=1.8; 14,15=7. 10: 2 3 = 4 5=15; 3,4=11; 5,6=13,14=7. 13: 2,3=4,5=15; 3,4=12,13=11; 5,6=13,14=7; 12,14= 1.8. Amine moieties: 8,9,10,13: N H , l ' = 1',2'=2',3'=3',4'=7. 11,lZ: NH, i t =1',2'=2',3'=7. I
1
1102
Journal of Natural Products
9
8
[Vol. 50, No. 6
1
H
5
H 7
by weak or medium-sized bands at 3055 and 3020 cm-’ (aryl-H stretching) as well as at 699 cm-’; acetylenic stretching vibrations were reflected in the resonances at 2200 cm-’. A weak to medium-sized band at 1362 cm-* was typical for a terminal methyl group attached to a double bond (compare 1, 3, 4 , 8, 9, and 11-13).Moreover, the number of E-oriented double bonds conjugated with the carbonyl of the amide group may be deduced from two or three bands in the >N-C=O/(C=C), stretching region (at 1672 and 1605 cm-’ or 1670, 1633, and 1611 cm-’) and from a sharp band in the =C-H out-of-plane region (at 995 or 950 cm-’; compare also compounds 8-13 and Experimental). The major component 1 showed four olefinic protons: an AB system at 6.33 and 6.80 ppm for a trans-orientated -CH=CH- element g= 15 Hz) with no further vicinal couplings ( = C-CH=CH-CO-) and a &orientated -CH=CH- element fJ=11 Hz) with an additional vicinal coupling of 7 Hz for the proton at 6.24 ppm and a long range
Nov-Dec 19871 Greger and Hofer:
1103
Unsaturated Isopentyl Amides I4
8 l
H
0
I
I
13
coupling of 1.8 Hz for the proton at 5.59 ppm. The latter coupling showed up very clearly in the resonance signal of the terminal methyl group at 1.95 pprn (dd,J=7 and 1.8 Hz). The separation of the two olefinic systems by four acetylenic carbon atoms followed clearly from the mass fragments m/z 143 (loo%, CH,-CH=CH-C EC-C ZCCH=CH-CO+, equivalent to M+-NHC,H,,) and m/z 115 (79%, 143-CO). The isopentyl amide structure for the NHC5Hll moiety followed from the 'H-nmr spectrum: a dt (appearing as a somewhat broadened pseudo q) at 3.37 ppm (-NH-CH,-CH,-), a d t (pseudo q) at 1.44 pprn (-CH,-CH,-CH
