J. CHEM. SOC. PERKIN TRANS. I 1989 Synthesis of the First Natural Host Germination Stimulant for Striga asiatica Melvyn V. Sargent * and Sirichai Wangchareontrakul Department of Organic Chemistry, The University of Western Australia, Nedlands, Western Australia, 6009 The germination stimulant, 5-methoxy-3-(8'Z,11 'Z)-pentadeca-8',11 ',I4'-trienyl benzene-I ,2,4-triol, exuded by Sorghum bicolor for the seeds ofStriga asiatica (witchweed) has been synthesized. A little understood feature of parasitism in plants is that the host may exude a stimulant which causes the germination of the parasite. Some of the host plants involved constitute food crops of vast economic and social importance. These include the legumes sorghum, maize, and millett which are staple foods in many tropical areas of the world where the plants are parasitized by various species of the genus Striga.' A potent germination stimulant for Striga species, the sesquiterpene strigol, was isolated from cotton which is not a natural host for Striga.2 According to a recent report, however, the first germination stimulant for Striga asiatica seeds, 5-methoxy- 3-(8'Z,11'Z)-pentadeca-8',11',14'-trienylbenzene-1,2,4-triol (17), was isolated in minute quantity from a natural host, Sorghum bicol~r.~This compound is active at 10-7~ concentration and is capable of defining the distance away from the host root at which Striga germinates.We now describe an efficient synthesis of this compound and the related biologically inactive quinone (18).We chose to adopt a convergent synthetic route to the target molecule (17) in which the (Z)double bond at the 8'-position in the side chain would be constructed by a Wittig reaction at a late stage in the synthesis. For this purpose we therefore required the phosphonium salt (6) (Scheme 1) and the protected aldehyde (15) (Scheme 2). The starting material for the synthesis of the phosphonium salt (6) was the known tetrahydropyranyl ether (1) of but-3-yn-1-01 which was allowed to react as its Grignard reagent with ally1 bromide in the presence of copper(r) chloride. Deprotection of the crude product gave the eneynol (2) as an oil (67), b.p. 45 "C at 0.01 mmHg. Partial reduction now gave pure (2)---* HCs CCH2CH2OTHP dienol (3) (89),b.p. 60 "Cat 0.5 mmHg.' This compound was now converted sequentially into the tosylate (4) (82),the iodo compound (5) (loo), and finally into the phosphonium iodide (6) (96),m.p.145-147 "C. The starting material for the synthesis of the aldehyde (15) was the phosphonium bromide (7)6 which as its derived ylide was caused to undergo a Wittig reaction with ethyl 7-oxoheptanoate.' The crude product was converted by hydrolysis and reduction into the acid (8) (loo), m.p. 6amp; 62 "C.Methylation now gave the ester (9) (9573, b.p. 200 "C at 0.01 mmHg, which on reduction afforded the alcohol (10) (loo), b.p. 230deg;C at 0.01 mmHg. This latter compound was protected as its benzyloxycarbonyl derivative (1 1) (100)which on oxidation with chromium trioxide under mild conditions supplied the quinone (12) (90) as yellow needles, m.p.40- 41 "C. Thiele acetylation of the quinone gave the triacetoxy compound (13) (91). The structure of this compound, and hence the regiospecifity of the Thiele reaction, was confirmed by a NOESY experiment. In the spectrum of compound (13) there was a strong off-diagonal interaction between the resonance of the aromatic proton and that of the methoxy group. Deprotection of compound (13) by hydrogenolysis gave the alcohol (14) (77) which on oxidation with pyridinium chlorochromate supplied the required aldehyde (15) (100). Wittig reaction between the aldehyde (15) and an excess of the ylide derived from the phosphonium iodide (6) gave the triene (16) (56) which on deprotection by treatment with lithium aluminium hydride gave the germination stimulant (17) (100)as an unstable oil the spectroscopic properties of which were in accord with the literat~re.~The stereochemical H2C= CHCH2CECCH2CH20H Z 1;H~C-CHCH~CH-CHCH~CH~OTSYH,C=CHCHZCH=CHCH~CH~OH vii Z + H2 C=CHC H2 CHsCHCH2 CH2 I _I_____) H2C= CHCHzC H =C HC H2CH2 PPh3I-(5) (6) Scheme 1.Reagents and conditions: i, EtMgBr, THF, Ar, 60 "C,45 min; ii, CuCI, CH,=CHCH,Br, Ar, 60 "C,45 min; iii, PPTS, MeOH, Ar, 55 "C, 18 h; iv, H,, 5 Pd/BaSO,, C,H,N; v, CHCI,, p-MeC,H,SO,Cl, C,H,N, 0 "C, 6 h; vi, NaI, Me,CO, 25 "C, 2 d; vii, Ph,P, MeCN, reflux, Ar, 2 d. 1172 J. CHEM. SOC. PERKIN TRANS. I 1989 OMe OMe OMe OMe 1,ii.iI i.iv Scheme 2.Reagents andconditions: i, BuLi, THF, Ar, 25 "C; ii, OHC(CH,),CO,Et, Ar, 25 "C; iii, NaOH, H20, MeOH, reflux, 5 h; iv, H,, 10 Pd/C, EtAc; v, MeOH, H2S04, reflux, 16 h; vi, LiAlH,, Et,O, 25 "C, 3 h; vii, CIOCOCH,Ph, C,H,N, PhMe, 0-60 "C, 3 h; viii, 4 equiv. CrO,, AcOH, H,O, 6-25 "C, 1.5h; ix, Ac,O, H,SO,, 25 "C, 12 h; x, H,, 10 Pd/C, EtAc, 2 h; xi, PCC, NaOAc, CH,Cl,,O-25 "C, 3 h; xii,4equiv. (6),BuLi, THF, -78 "C, Ar, 0.5 h; xiii, HMPA, THF, -78 "C, Ar, 2 h; xiv, THF, LiAIH,, Ar, 25 "C, 10 min; xv, PhH, 1 aq. FeCl,, 15 min. homogeneity of this material was confirmed by the I3C n.m.r. spectrum.8 Mild oxidation of the stimulant provided the quinone (17) as yellow plates (loo),m.p. 37-39 "C.Again the spectroscopic data for this compound were in accord with the Iiterat~re.~ References 1 A.W. Johnson, Chem. Br., 1980,16,82. 2 C. E. Cook, L. P. Whichard, M. E. Wall, G. H. Egley, P. Coggon, P. A. Luhan, and A. T. McPhail, J. Am. Chem. Suc., 1972,94,6198. 3 M. Chang, D. H. Netzly, L. G. Butler, and D. G. Lynn, J. Am. Chem. Sue., 1986, 108,7858. 4 S. C. Jain, D. E. Dussourd, W. E. Connor, T. Eisner, A. Guerro, and J. Meinwald, J. Org. Chem., 1983,48, 2266. 5 This compound has been prepared previously as a mixture of stereoisomers: B. B. Snider, G. B. Philips, and R. Cordova, J. Org. Chem., 1983, 48, 3003; L. Crombie and R. D. Wyvil, J. Chrm. Suc., Perkin Trans. I, 1985, 1983. The stereochemical homogeneity was confirmed by the I3C n.m.r. spectrum (assignments assisted the DEPT technique) 6,(75.5 Hz; CDCI,) 30.56 (C-2), 31.47 (C-5), 62.02 (C-l), 114.73 (C-7), 126.37 (C-4), 129.77 (C-3), and 136.65 (C-6). 6 E. Reimann, Chem. Ber., 1969,102,2881. 7 R. K. Clark, Jr., and J. R. Schenck, Arch. Biochem. Biophjv., 1952,40, 270. 8 I3CN.m.r. spectrum: 6,(75.5 MHz; CDCI,) 23.83 (C-l'), 25.56 (C-lo), 27.22 (C-7'), 29.06, 29.25. 29.44, 29.63, and 29.66 (each CH,), 31.51 (C-13'), 56.56 (OMe), 97.95 (C-6), 114.67 (C-15'), 116.69 (C-3), 126.78, 127.51, and 129.31 (C-9', C-ll', and C-12'), 130.46 (C-8'), 135.82, 135.99, 137.70, and 139.88 (C-1, C-2, C-4, and C-5), and 136.83 (C-14'). Received 8th November 1988 (Accepted 22nd February 1989); Paper 9/00805E
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