Chiroptical studies. Part LXXXVII. Circular dichroism of some sparteine alkaloids

摘要

1974 2565Chiroptical Studies. Part LXXXVII.l Circular Dichroism of SomeSparteine AlkaloidsBy William Klyne," P. Molly Scopes, and R. Nigel Thomas, Westfield College, Hampstead, London NW3 7STJerzy Skolik, Jacek Gawrosriki, and Maciej Wiewiorowski, A. Mickiewicza University, Poznari, PolandC.d. data have been recorded for seventeen compounds of the sparteine series related to 11 P-sparteine (a-iso-sparteine) and 1 1 a-sparteine. The chromophores involved are the tertiary amine and NN-dialkyl-lactarn systems ;the compounds studied include eight amines, eight amino-lactams, and one dilactam.THE sparteine alkaloids are of considerable interest forchiroptical studies because they contain chromophoresof two different types (NN-dialkyl-lactam and tertiaryamine) in a rather rigid system of four fused six-membered rings (1).The skeleton may be consideredl Preceding papcr in the Westfield series, hitherto entitled' Optical Rotatory Dispersion and Circular Dichroism,' PartLXXXVI, L. Bartlett, D. N. Kirk, and P. M. Scopes, J.C.S.P e r k k I , 1974, 2219.as two quinolizidine systems fused together, or as adiazabicyclo3.3. llnonane which has been extended byone six-membered ring at each end (for general referencessee ref. 2). The chiroptical properties of the amide' The Alkaloids,' ed. R. H. I?. Manske, Academic Press, NewYork and London: N. J. Leonard in vol. 3, 1963, p. 119, and vol.6, 1960, p. 253; F. Bohlmann and D. Schumann in yol. 9, 1967,p. 191; R. K. Hill in ' Chemistry of the Alkaloids, ed.S. W.Pelletier, Van Nostrand, New York, 1070, pp. 418-4222566 J.C.S. Perkin Ichromophore have been much studied, though not inthe substitution pattern found here ; few chiroptjlcalstudies on tertiary amines are available. Some 0.r.d.measurements on sparteine derivatives have beenrep~rted.~Conjiguration and Nomendatwe.-The absolute con-figurations of compounds in the group are known fromstudies by Okuda.* Most of the known naturallyoccurring compounds have the configurations at C-6,C-7, and C-9 shown in formula (2); in particular, theyhave the 6p(H)-configuration (in terms of steroid con-ventions). The configuration at C-11 is variable, andwe suggest that for semisystematic nomenclature thestem-name ' sparteine ' should imply the configurationsat C-6, C-7, and C-9 shown in (2), i.e.(6R,7S,9S), andthat the configuration of the hydrogen atom (or anygroup replacing hydrogen) at C-11 should be stated asa or p, following the pattern employed for ~ter0id.s.~Thus compound (3), hitherto known simply as 'spar-teine,' becomes 11 a-sparteine ; ' cc '4sosparteine (2)becomes 11 P-sparteine.Conformation and Symmetry.-1 1 p-Spaxteine (2) is arigid molecule with an all-chair conformation in allcircumstances (2A) ; its skeleton shows C, symmetry,and may be represented as part of a diamond network.The llcc-sparteine system (3) can exist either in an' all-chair ' conformation (3A) or in a conformation inwhich ring c is a boat, and the remaining three ringsare chairs (3B). Extensive studies on the conform-ations of the sparteine alkaloids by i.r.and n.m.~.~*'spectroscopy have been carried out.The conformation of any particular 11 a-compounddepends on the nature and position of ring substituents,on the state (crystalline or in solution), and on thecharacter of the solvent. For many lla-compoundsn.m.r. and i.r. measurements indicate the all-chairconformation in polar solvents, but the ' c-boat ' con-formation in non-polar solvents ; in certain cases,however, the ' c-boat ' conformation may occur also inS. Iskanderov and S. Yu. Yunusov, Khim. prirod. Soedinenii,1970,8,494 (Chem. Nut. Compounds, 1970,6,519) ; S. Iskanderov,R. A. Shaimardanov. and S. Yu. Yunusov, ibid., 1971, 7, 636(Chem. Nut. Compounds, 1971, 7, 615).4 S.Okuda, K. Tsuda, andH. Kataoka. Chem. a7d Ind., 1961,1116, 1751; cf. W. Klyne and J. Buckingham, An Atlas ofStereochemistry,' Chapman and Hall, London 1974, p. K21.1.U.P.A.C.-I.U.B. Rules of Steroid Nomenclature, PureAppl. Chem., 1972, 31, 286.(a) P. Baranowski, P. Skolik, and M. Wiewiorowski, Tetra-hedron, 1964,20, 2383; (b) M. Wiewiorowski, 0. E. Edwards, andM. D. Bratek-Wiewiorowska, Canad. J . Chem., 1967, 45, 1447;(c) J. Skolik, P. J. Krueger, and M. Wiewiorowski, Tetrahedmn,1968, 24, 6439; ( d ) J. Skolik, M. Wiewiorowski, and K. Jedrze-jczak. Bull. Acad. polon. Sci. Sir. chim., 1969, 17, 201; (e) J .Skolik, M. Wiewiorowski, and P. J. Krueger, J . Mot. Strztcture,1970, 5, 461.polar solvents as a result of intramolecular hydrogenbonding (cf.p. 2567).It had been hoped that c.d. measurements in arangeof solvents would provide further evidence regardingconformations; the c.d. results, however, show no clearcorrelation with the i.r. studies. In the present state ofknowledge of the c.d. behaviour of arnides and oftertiary amines, our c.d. results are therefore presentedon their own in an empirical fashion.The Bis-(tertiary amines) .-These compounds include11 a-sparteine, 11 P-sparteine, and their hydroxy-deriva-tives, in which the only chromophores are the tertiarynitrogen atoms at the bridgeheads of the quinolizidinesystems. Earlier data on the U.V. absorption of tertiaryY( 2 1 ( 2A 1 all-chair,'Ilp-H( 3A 1 all-chair, llcc-Hamines are summarised(38 ) chair, chair,Absorption C.d. Absorption C.d.Compound1 l(3-Sparteine(' a '-Isosparteine)1 la-Sparteine(Spar teine)4a(eq) -Hydroxy- 1 la-sparteine12P(ax)-Hydroxy-l la-sparteine13a(eq) -H ydroxy- 1 1 a-sparteine13p(~x) -Hydroxy-1 la-sparteineLupinineEpilupinineE368081807300520081007300710046004300A/nm240210205198198201201198205A t + 2-79- 8.89+1! - 0-39 + 3.12$2.11-0.17 + 0.78+0-12 - 0.40 + 1-98-2.8!- 0.36 + 3.98- 0.54+3*61 + 0.29- 1-2 I + 0.05- 0.35 + 0*4!A/nm245217194236202-208189238220234213198186237208237208209195225204185 A/nm A t1880 225 + 1.224800! 202 - 3.55- 0.063600 199 + 0.59 + 1.6!3500 206 + 0.46- 1.063850 203 + 1.683300 203 + 1-98+0*11A/nm230206242208195200202197201211* None of the compounds listed in this Table showed any c.d.in acidic methanol. t All A values are maxima except thosemarked ! (lowest wavelength measured).six of their hydroxy-derivatives. We find for 11 p-sparteine an absorption maximum in hexane a t 210 nm( E ca. 8180) with a shoulder at 240 nm (e 3680); othermembers of the series with and without hydroxy-groups show similar absorption bands at about 200-205 nm, but in most cases the shoulder at 240 nm cannotbe detected. Lupinine and epilupinine (a), which areuseful models for one-half of the sparteine skeleton,show absorption at about 200 nm with E ca.4000.l2 R. G. Kostyanovsky, I. M. Gella, V. I. Markov, and 2. E.Samojlova, Tetvahedron, 1974, 30, 39.l3 E. Tannenbaum, E. M. Coffin, and H. Harrison, J . Chem.Phys., 1953,21, 311; L. W. Pickett, M. E. Corning, G. M. Wieder,D. A. Semenow, and J. M. Buckley, J . Amer. Chem. Soc., 1953, '45,1618.l4 J. C. Craig and S. K. Roy, Tetrahedron, 19ti5, 21, 401; J. C.Craig, ' Some Newer Physical Methods in Structural Chemistry,'ed. R. Bonnett, London, 1967, p. 170; H. C. Beyerman, L. Maat,J. P. Visser, J. C. Craig, and R. P. K. Chan, Rec. Trav. chim., 1969,88, 1012; G. Fodor, E. Bauerschmidt, and J. C. Craig, Canad. J .Chem., 1969, 47, 4393; H. C. Beyerman, S. van den Bosch, andJ. H. Brenker, Rec.Trav. chim., 1971, 90, 755; H. C. Beyerman,B. S. L. Bordes, L. Maat, and F. M. Varnaar, ibid., 1972, 91,1441.bands disappeared, as expected, on acidification of amethanolic solution. 11 p-Sparteine is considered firstbecause of its inherent C, symmetry; it shows in liexanea moderate positive c.d. band at 245 nm, and two strongbands at 217 and r h E A/nm AE A/nm E A/nm A5 i A/nin17,80017,2507 7006OOsh2200530sh570018,00010,600770sh13,400215209207250208265211206210241209+ 5.30- 4-37- 4.68 -+ 4.32- 9.28 + 6-95 + 0.80sh + 1.16+ 1.05~h- 2.67-/- 3.03- 7.20 + 3.31- 7-34 + 8.44 + 0.53- 1.05 - 1-42 -+ 4.25- 7-98+5*0! + 0.88- 10.2+11*7!- 3.32 + 2.37sh+ 3-82+ 7.90+5-7!- 7.14-5.10236215193235208190245235208254235208241210190233209298a24321119424422018523321520723621820519316,20018,0006100GO0085008OOsh21001200sh620018,70011,9007400210205'1 1211205255211260209205206211+ (3.96 - G.96+ 5.83- 6.17$- 4.80- 4.45-b 5.49- 7.45- 0.21 + 1.48- 2.094- 0.62- 0.56- 1.47-f- 1.33- 1-95+3.3!- 6-95 + 6.04- 5.24+5.4!+ 2.46+ 2.7 !- 1.43d3 999198224200223200224197259 C225207225206293 d246212195220202226206223210197-0.26 264+3-64 333 -0.04 26212,900 207 -10.2 216 13,200 209 +7.92 220+22-8 204 +7-7! 206Salt in methanol aC.d.:I bsorptionE Alnm AE t A/nm+8.35 22712,500 207 -17.0 202+6*52 22415,400 205 -9.26 200+5*55 222--8*9! 197+6*28 224-8.63 197-2.53 257*+1-89 220-23.0 203-2.18 254*-21.0 201+590 255-7*2! 20016,900 207 -12.4 203+4*83 227-1.22 255+3*4! 206-0.82 228+4*08 205-0.05 264f8-13 219+7.68 2067 All 4~ values are maxima except those marked sh (shoulder) or ! (lowest wavelength measured).a Salts were formed by adding an excess of HCl to the methanolic solution of the base, except in two cases marked * where thecrystalline perchlorate was used.13a-Hydroxy- 15~-(5-hydroxymethyl-2-furyl)-2-oxo-l la-sparteine was also examined inmethanol AE + 7.94 (228 nm), -3.97 (201 nm), -6.2! (195 nm) and in acidic methanol AE + 10.8 (225 nm), -8.6 (201 nm);the compound was insoluble in hexane.Measurcd on base liberated from the perchlorate. Ketonic n + x* band.even in hydroxylic solvents. Lupinine (4; P-CH,OH)and epilupinine (4; a-CH20H) show c.d. bands whichseries at all four possible positions (2, 10, 15, and 17),but in the more symmetrical 11P-sparteine series onlythe 2-oxo-compound is available. Various hydroxy-2-oxo-1 la-sparteines have been studied, and also 2,13-dioxo-1 la-sparteine, in which the 13-oxo-group is ofnormal ketonic character.There is no reason to suppose that the c.d. behaviourof the substituted amide group would be significantlyaltered in acidic methanol; the c.d. bands of amines atabout 200 nm are obliterated by acid,13 and the observedc.d. of the monolactam monoamino-compounds in acidis presumably essentially that of the lactam chromo-phore alone (perturbed by quaternary nitrogen).deO" m,30( 4 ) ( 5 1are much less intense than those given by the bis-(tertiary amine) skeleton in 11 cc- and 11 P-sparteine.Lactatla-Tertiary Amines (Oxosparteitzes) .-Several im1974Literature data on the U.V. absorption of lactams aresparse.ls~~~ We found for three of the lactams studiedU.V.maxima at 205-207 nm (cmx. 12,000--17,000) inacidic methanol, and rather more intense maxima atsimilar wavelengths in (neutral) methanol and inhexane.No extensive collection of c.d. data for lactams isavailable; some recent papers, in which references toearlier work may be found are given as refs. 20-25(as well as 18 and 19); very few of the compoundsconsidered in these references are NN-dialkyl-lactamsof the kind found in the sparteine series.C.d. studieson acetamido-derivatives of chiral amines, whichappear to show a surprising measure of conformationalrigidity, are also noted.2-0xo-conzpo.unds. We consider first the 2-oxo-l l a-and l l p-sparteines (5) carrying no other substituents;each compound gives, down to about 200 nm, the samec.d. pattern in hexane, in methanol, and in acidicmethanol; viz. a strong positive band at about 225-230 nm and a strong negative band at about 200-215nm. A further band at about 190 nm is negative forthe llp- and positive for the lla-compound. It wouldbe tempting to consider the first two bands as a coupletdue to interaction between two chromophores thetransitions of which are of approximately the sameenergy.However, such a hypothesis is untenablebecause the apparent couplet is present with evengreater intensity in acidic methanol, in which the tertiaryamine group has been quaternised and shows noabsorption in the region of 200 nm. The coupledoscillator or exciton chirality treatment has beenapplied primarily to compounds containing a pair ofidentical or almost identical chromophores, by, forexample, Mason 26 (cf. refs. 27 and 28); it has recentlybeen applied to pairs of chromophores, the members ofwhich are of significantly different character althoughthe energies of the transitions involved are ~ i m i l a r . ~ . ~ ~The 13a- and 13P-hydroxy-2-oxo-1 la-sparteines showc.d.curves generally similar to those of the parentoxo-compound. The two 17P-hydroxy-substituted 2-oxo-llct-sparteines (6) as salts have an additionalCotton effect at about 255 nm which is not present forthe other 2-oxosparteines ; the short-wavelength nega-tive maxima near 200 nm are very much more intense(A -20) than those for the rest of the series. TheH. Basch, 31. B. Robin, and N. A. Kuebler, J . Chem. Phys.,1968, 49, 5007.C. G. Overberger, G. Montando, J. Sebenda, and R. A.Veneski, J . Anzer. Chem. SOC., 1969, 91, 1256.*O J. A. Schellman, Accounts Chcm. Xes., 1968, 1, 144.*l D. W. Urry, Ann. Rev. Phys. Chent., 1968, 19, 477.22 H. Wolf, Tetmhedrogz Letters, 1965, 1075; 0. Cervinka, L.Hub, 1:.Snatzke, and G. Snatzke, Coll. Czech. Chem. Comm., 1973,88, 897.f3 W. Klync and P. M. Scopes in ‘ Fundamental Aspects andRecent Developments in O.R.D. and C.D.,’ ed. F. Ciardelli and1’. P. Salvadori, Heyden, London, 1973, p. 126.24 M. Goodman, C. Toniolo, and J. Falcetta. J . Amer. Chem.SOC., 1969, 91, 1816.25 H. Rehling and H. Jensen, TetvahedrovL Letters, 1972, 2793;H. Ogura, H. Takayanagi, K. Kubo, and K. Furuhata, J . Amer.Chew. SOC., 1973, 95, 8056; H. Ogura, H. Takayanagi, and K.Furuhata, Ckcm. LrtteiTs, 1973, 387.maximum near 255 nm presumably arises from tlieprotonated carbinolamine structure “-16, C( 17)-OH,which exists as an iminium salt (Nf=C) in the presence ofstrong acid (for chiroptical properties of C=N groupssee ref.31a).( 6 )2,13-Dioxo-lla-sparteine (7) has: in addition to thelactam group and the tertiary nitrogen, a ketoniccarbonyl chromophore at C-13 which gives rise to amoderate negative Cotton effect near 295 nm (n _t X*transition). The molecule is believed to exist in aconformational equilibrium containing equal proportionsof the all-chair and ‘ c-boat ’ conformers; for eitherconformation the observed negative Cotton effect is inaccordance with the prediction of tlie Octant Rule, asrefined recently.32 (0.r.d. measurements for a 40x0-sparteine have been reported.) On addition of acidto the methanolic solution the ketonic Cotton effect forcompound (7) disappears, owing to hemiacetal form-ation; the form of the c.d. curve is then the same asthat for 2-0x0-1 la-sparteine and its hydroxy-derivatives.10-0x0-1 la-sparteine (8) gives astrong apparent c.d.couplet of opposite sign to that ofthe 2-oxo-analogue in hexane and methanol; this maybe a reflection of the fact that the surroundings of theamide chromophores in the two compounds (i.e. rings Aand B) are quasi-enantiomeric. However, the c.d. curvefor 10-oxo-lla-sparteine in acidic methanol is of thesame sign as for the 2-oxo-analogue. The c.d. curves for15-oxo-lla-sparteine are of opposite sign to those forthe 2-oxo-analogue ; the amide chromophore here ispart of the CD ring fragment of the molecule and (if wedisregard possible conf ormational differences) is of atype quasi-enantiomeric to that in the 2-oxo-compound.The c.d.results for 17-oxo-lla-sparteine are distin-guished from those of the 2-oxo-analogue by the smallermagnitudes of the Cotton effects; the signs are the sameas those of the bands for the 2-oxo-compound in hexaneand in methanol; in acidic methanol the signs arereversed.Other oxosparteines.26 S. F. Mason and G. W. Vane, J . Chetn. SOC. ( B ) , 1966, 370;for a list of applications and correlations with the Bijvoet X-raytechnique, see S. F. Mason, J.C.S. Chem. Comm., 1973, 239.27 0. E. Weigang, jun., and M. J. Nugent, J . Amer. Chem. SOC.,1969, 91, 4555.28 N. Harada and K. Naksnishi, Accounts Chem. Res., 1972, 5,257.20 N. Harada, J . Amer. Cltem. SOC., 1973,95, 240; M. Koreeda,N. Harada, and I(. Nakanishi, ibid., 1974, 96, 266.30 G.Ohloff, E. Otto, V. Rautenstrauch, and G. Snatzke, Helv.Chim. Ada, 1973, 56, 1874.31 P. CrabbC, ‘An Introduction to the Chiroptical Methods inChemistry,’ Mexico 1971, (a) p. 64; (b) pp. 54-56.32 D. N. Kirk and W. Klyne, J.C.S. Perkist I , 1974, 1076.33 S. I. Goldberg and R. F. Moates, J . Org. Chem., 1967, 32,1832.a4 C. Djerassi, L. A. Mitschcr, and B. J. Mitscher, J . Anzrr.Chem. SOC., 1959, 81, 9472570 J.C.S. Perkin IDiZactam. The only dilactam available is 2,17-dioxo-lla-sparteine (9). The c.d. curve in methanol is un-usual in showing two maxima of the same sign (positive)at about 220 and 206 nm; as expected it is virtuallyunchanged by addition of acid. In contrast, the c.d.3 m 2 NI APh( 9 ) (10)curve in hexane shows a very strong ‘ couplet ’ (A-10, 216 nm; +22, 204 nm).Data for this compound (described as ‘ D-OXO-lupanine ’) in other solvents have been published.352-AryZs~arteines.-C. d.data for 2a-phenyl-1 I a-sparteine (10) and the corresponding 2,3-didehydro-compound (which are insoluble in hexane) are presentedfor methanolic and acidic methanolic solutions (Table 3).2oc-Phenyl-lla-sparteine shows a small positive Cottoneffect centred at 261 nm, with the vibrational finestructure characteristic of the aromatic nucleus. Thesign of this lLb Cotton effect, is as expected, unaffectedby protonation. Maxima below 220 nm arise from thesuperposition of Cotton effects due to the aromaticnucleus (IL, transition) and the tertiary nitrogen.The 2,3-didehydro-compound exhibits in methanol aseries of overlapping Cotton effects with positive maximaat 277 and 246 nm (styrene chromophore) 31b and ashoulder at 219 nm.On addition of acid there is a35 F. A. Bovey, Pure Appl. Chem., 1968, 16, 417.marked change in the c.d. curve; the first two maximaare negative (at 267 and 255 nm) and the next is positiveat 213 nm with a shoulder at 222 nm.TABLE 3C.d. of arylsparteinesFree base(MeOH)r A€2-Phenyl-lla-sparteine (10) + 0.23 + 0.24 + 0-23+0-17 + 1.07- 5.62sh- 8.04 !2,3-Didehydro-2-phenyl- + 6.041 la-sparteine + 7.81 + 2.84sh- 4.26 IX/€lm’268261255248219202195277246219203This inversionSalt(MeOH)bAc A/nm+0*17 268+0*19 261+0*13 255+0*09 248-0.80 215-1.89 267-1.30sh 255+2*37sh 222+3*20 213of sign is presumably associated partly with the isomeris-ation of the double bond from 2,3- to 1,2- (which isknown to occur on protonation of 2,3-didehydro-2-phenylsparteine), and also with the related change inconformation from CD boat-chair to all-chair.EXPERIMENTALAll compounds examined were available from thecollection of M. W. in Poznafi. Compounds available as thefree base were examined in hexane and in methanol; theywere converted into salts by the addition of aqueous10M-hydrochloric acid (1 drop) to the rnethanolic solutionof the base (ca. 5 ml}; two compounds available only asthe perchlorate were converted into the free base bydissolving the salt in water, adding alkali, and extractingthe base into ether.C.d. curves were recorded on a Jouan Dichrographe 185with solutions of concentration 1 mg ml-l or less and pathlengths 10 mm or less. U.V. absorption data were re-corded for the same solutions on a Unicarn SP 800 spectro-meter.The London authors thank the S.R.C. for a researchgrant, and the Poznafi authors thank the Polish Academyof Sciences for support.4/1616 Received, 2nd August, 1974