The chemistry of hop constituents. Part XL. Structure of a five-membered-ring oxidation product of colupulone

摘要

36 J.C.S. Perkin IThe Chemistry of Hop Constituents. Part XL.l Structure of a Five-membered-ring Oxidation Product of ColupuloneBy (Mrs.) Jean Coates and Derek R. J. Laws, Brewing Industry Research Foundation, Nutfield, Surrey RH1 4HYJohn A. Elvidge," University of Surrey, Guildford GU2 5XHOxygen acts on colupulone in petroleum at 60" to give 5-hydroxy-5-isobutyryl-3,3-bis-(3-methylbut-2-enyl)-cyclopentane-l,2,4-trione, which wetfind present in old hops. Cohulupone i s evidently an intermediate, but thenew product appears not to be an intermediate in the oxidation of cohulupone to hulupinic acid.THE hop resin constituent colupulone (I) is rapidlyoxidised in stored hops and when oxygen is passedthrough its solutions. Whilst there may be cyclisationof a side chain onto an oxygen substituent of the ring,loss of a side chain, and introduction of hydroxy-groups,the six-membered carbocyclic ring either persists orcontracts to a five-membered ring.Products of the firsttype include benzodipyrans,2 dihydroben~opyrans,~ anddihydrobenzof ~ r a n s . ~ Ring- contraction products includecohulupone (11) and hulupinic acid 5 (111) (both minorconstituents of hop resin 8,7), and a cyclopentafuran and acyclopentapyran.8n n(rn) UYIWe now describe the isolation and characterisation ofa new oxidation product (IV), obtained by passingoxygen through a solution of colupulone (I) in lightpetroleum at 60deg;.9 It forms yellow prisms, has thecomposition C,,H,O,, and gives a U.V. spectrum likePart XXXIX, M.Collins and D. R. J. Laws, J.C.S. PerkinD. M. Cahill and P. V. R. Shannon, J . Chem. Soc. ( C ) , 1969,E. Byrne, D. M. Cahill, and P. V. R. Shannon, J . Chem.D. Wright, J . Chem. SOC., 1963, 1769.J. S. Burton, R. Stevens, and J. A. Elvidge, J . Chem. SOC.,I , 1973, 2013.938.SOC. (C), 1970, 1637.1964,952.that of cohulupone (11) except that the maxima do notshift when alkali is added to the solution. Evidently thenew product has a five-membered ring and a p-tricarbonylsystem, similar to cohulupone, but is incapable of enolis-ation. In contrast to cohulupone, which shows en01hydroxy-absorption at 3450 cm-l,lo the new productshows a reasonably sharp hydroxy-band at 3350 cm-1.These observations suggest the structure (IV) in whichenolisation is blocked by a hydroxy-group.Strongsupport comes from the lH n.m.r. spectrum. In theT 9.0-50 region, the spectrum closely resembles that ofcohulupone (11) but at low field there is no sharp signalfrom a chelated enolic proton, only a very broad one-proton signal centred at 7 0.3. When the solution isshaken with water, separated, and re-examined, the lastsignal has moved upfield to T 3.4 and is less broad, be-haviour typical of a non-chelated hydroxy-group.We conclude that the new oxidation product of colu-pulone (I) is 5-hydroxy-5-isobutyl-3,3-bis-(3-methyl-but-2-enyl) cyclopentane-l,2,4-trione (IV) .In agreement with this constitution, the compound isobtained from cohulupone (11) by oxygenation inpetroleum. Although the yield is low, it is much higherthan from colupulone (I), suggesting that in the oxidationof the latter to the new product (IV), cohulupone (11) isan intermediate.Attempts to oxidise the new product(IV) further to hulupinic acid (111), by oxygen in boilingethan01,~ failed, compound (IV) being recovered (68).Thus the new compound (IV) appears not to be an inter-mediate in the oxidation of cohulupone (11) to hulupinicacid (111) but is presumably a parallel oxidation product.The new compound (IV) is present in old hops, asfound by extraction, trimethylsilylation, and separationby g.1.c. The complex chromatogram shows a peak6 R. Stevens and D. Wright, J . Inst. Brewing, 1961,67,496.7 J. S. Burton and R. Stevens, J . Inst. Brewzng, 1965,71, 51.8 R.Van den Bossche, M. Anteunis, M. Vandewalle, and 31.9 Cf. P. R. Ashurst and J. A. Elvidge, J . Clzem. SOC. (C), 1966,10 L. 0. Spetsig and M. Steninger, J . Inst. Brewing, 1960, 66,11 S. Forsen, M. Nilsson, J. A. Elvidge, J. S. Burton, and R.Verzele, J.C.S. Perkin I , 1972, 1699.675; B. E. Connett and J. A. Elvidge. ibid., 1968, 1193.413.Stevens, Acta Chem. Scand., 1964, 18, 6131974 37identical in retention time with that from the authentic tri-methylsilyl derivative of compound (IV) . Furthermore,separation of ethereal hop extract on a t.1.c. plate, elutionof the appropriate zone, trimethylsilylation, and theng.1.c. separation, gives (apart from the solvent peak) astrong peak in the chromatogram, with the retention timefor the derivative of compound (IV).This peak is en-hanced by the prior addition of compound (IV) to thehop extract.Having a somewhat bitter taste, the new compoundpossibly contributes to the bittering properties of hops.EXPERIMENTALU.V. and i.r. spectra were measured with a Pye-UnicamSP 1800 and a Perkin-Elmer 157G spectrophotometer,respectively. 1H N.m.r. spectra were recorded with aPerkin-Elmer R10 (60 MHz) spectrometer.Oxidation of Co1upuZone.-Colupulone (I) (15 g) wassuspended in light petroleum (800 ml; b.p. 60-8O0) andplaced in a jacketed tube (4 x 100 cm). The mixture wasmaintained a t 60" by circulating water through the jacketwhile oxygen (6 1 11-1) was passed through the petroleumsolution for 18 11. The mixture was cooled to 20" thenfiltered, and the filtrate was evaporated to leave a yellow oil(12.2 g).A portion of this oil (2.0 g) was chromatographedon a column of silicic acid (60 x 2.5 cm), and was elutedwith hexane-ether (400 ml; 9 : 1) followed by hexane-ether(200 ml; 6 : 1) ; 50 ml fractions were collected. Fractions8-10 gave a pale yellow oil (0.9 g) which crystallised a t 0".The yellow crystals were washed with light petroleum (b.p.40-60') and dried to give 5-hydroxy-5-isobuty~yZ-3,3-bis-(3-rvleth3/Zbut-2-enyZ)cyclopentane-1,2,4-t~ione (IV) (40 mg) , m.p.107" (Found: C, 68.0; H, 7.7. C,,H,,O, requires C, 68.3;H, 7-8y0), Lx. (acidic EtOH) l2 255 and 325 nm (E 9160 and0130), A,, (alkaline EtOH) l2 253 and 324 nm (E 12,660 and8900), vmx. (Nujol) 3350 (OH), 2980 and 2940 (CH), 1755,1710, 1695, and 1670 (CO), 1460s, 1380s, 1325w, 1270w,1150w, 1115w, 1095w, 1080, 970w, and 850 cm-l, T (CDCl,)8-89 (d, J 6-7 Hz, Me, of acyl group), 8.44 (s, 2 x Me, of alkyll2 J.A. Elvidge and D. R. J. Laws, J . Chem. SUG. (C), 1968,1193.groups), 7.59 (d, J 8 Hz, 2 x CH,), 6-31 (septet, J 6.7 Hz,CH of acyl group), 5.17 (ca. t, 2 x CH= of alkyl groups), and0.3 (1.8 p.p.m. broad, OH).Oxidation of CohzcZzcpone.-Freshly distilled cohulupone(200 mg) in light petroleum (10 ml; b.p. 60-80") wasoxidised as for colupulone. Evaporation of the solution lefta pale yellow oil, which at 0" afforded yellow prisms of com-pound (IV) (15 mg), m.p. and mixed m.p. 107".Detection of Compound (IV) in Old Hops.-NorthernBrewer hops (100 g) from 1965 growth were extracted withether (4 1) for 18 h, and the extract was concentrated (to 500ml), treated with charcoal (5 g), and filtered.A portion(0.25 ml) was streaked onto a t.1.c. plate (20 x 20 cm)coated with Kieselgel H (0.2 mm thick), and compound (IV)was used as a marker. After development with benzeneether (16 : 1) the chromatogram was allowed to dry, and themarker chromatogram (only) was sprayed with 1 yo iron(II1)chloride in methanol to reveal, as a yellow spot (RP 04), theposition of compound (IV). The corresponding zone in thehop-extract chromatogram was removed from the plate,eluted with methanol (20 ml) for 2 h; the extract wasfiltered and dried (MgSO4). The combined extract from sixplates was evaporated, and the residue shaken with NO-bis-(trimethylsily1)acetamide (100 p1) for 1 h. A portion (1 p1)was then chromatographed in nitrogen (46 ml min-l) on acolumn (9 f t x 0.25 in) packed with 3 methyl silicone gumon Diatomite CQ (100-120 mesh) (temperature programme100-300" at 30" min-l; flame ionisation detector). Thechromatogram showed a peak with the same retention time(487 s) as the trimethylsilyl derivative of compound (IV).The former peak was appropriately enhanced when com-pound (IV) was added to the original ethereal hop extractand the procedure repeated.A portion of the ethereal hop extract was treated withNO-bis(trimethylsily1)acetamide and the mixture wasexamined by g.1.c. as before. In the complex chromatogramthere was a small peak with the same retention time (487 s)as the authentic trimethylsilyl derivative of compound (IV).We thank Dr. C. E. Dalgliesh for his interest.3/1611 Received, 31st JuZy, 1973