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Tetrahedronetters o. 7, pp.19-25,979. er&awn Press td. Printed nGreat ritain.

G.Stereochemical

KPOXIDATIORXPRRIKRRTS K VIVO ITEDRRYDROHYOSCYAMIREAKDRFLATEDOMPOlJRDSFodor, . Romeike, . Janzrd nd I. KoczorLaboratory,he Hungarian oademy f Scienoes, udapestand

The Research nstitute or Plant bysiologg,heGatersleben,ermany(Reoeived 1 YAW 1959)

Berlin cademy of Scienoes,

A PRRVIOUS aper f one of ml reported n the ability f overground rgrrneof Datura erox , to convert yosoyamine I) into (-)aoopolamine,.e.hyoscine IV), Prom the results f the synthesis f scopolamine*3 in-volving poxidationf tropenyl oetate2 nd (-)tropenylropoylate3(6.7-dehydrohyoacyamine),ne of us (G.F.) uggested4 5hat the conversionof hyoscyamine nto yoeoine akee he same athway.

In order o check he correctnessf this assumption eeding xperi-ments ith (-) 6.7-dehydrohyoscyemineIII) ave been carried utessentiallyy the same teohnique s used for hyoaoyamine.' atura erox ,

A. Romeike, lora $& 67 (1956).0. Fodor, . T&h, I. Koozor, . obb and I. Qinaze, hem. Ind,764 (1956); . Chem. oo, In press (1959).G. Fodor, . T&h, A. Romeike, . Vinose, . Dobd and 0. Janzeb,Anzev. hem, 2,678 (1957).G. Fodor, bhandl. tsch. kad. iss. l. Chem,93 (1957).0. Fodor. etrahedron, 86 (1956).

19

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20 Epoxidation experimente of dehydrohyoscyamine

grafted on Cynhomandra betacea (CAV) SENDTN, is practically void ofalkaloids. Branchee of half a year old Datura soione were cut (green weight15.5 g) and placed into a 1.5.103 molar solution of (-) 6,7-dehyaro-hyoscyamine acetate of pH 6.7.

After a week, the alkaloids were extracted and separated by paperchromatography. The fraction which showed the Rf value oharacteriatic for20hyoecine (IV) was converted into the picrate, m.p. 175, [a]D = -6.5(0 = 2; dimethyl formamide). (Found: C, 52.2; H, 5.0; N, 10.5.C23H24011N4 requires C, 51.9; H, 4.5; N, 10.596) identical in every respect

with an authentic sample and with the compound obtained from feedingexperiments with (-)hyoscyamine (Found: C, 52.0; H, 4.5; N, 10.196).

Decisive evidence for the intermediate role of tropenyl (-)tropoylate(II I) in the epoxidation of hyoeayamine was expected to be furnished byisolating 6.7-dehydrohyoscyamine after feeding of Datura ferox withhyoacyamine in the presence of oxidation inhibitors, e.g. calcium nitrateor cyeteine (cf. Romeike6),

In this case, however, no definite ring of tropenyl tropoylate couldbe found with certainty on paper ahromatograme, the main product being ahitherto unknown tropanol ester6 which la alao formed to a slighter extentalong with hyoscine in normal epoxidations. The alkamlne of this alkaloid U6

6 A. Romeike and L. Zlmmezvnan, Naturwisaenachaften 42, 187 (1958).7 The absolute oonflguration of valerine haa been determined byG. Fodor, I . Vlnose and J . T6th, Exoerientia 2, 183 (1957).

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Rpoxldetion xperiments f dehydrohyoeayamine 21

1s not identical ither with tropine or with pseudotroplne, eloldine,aaopine or oscine. Flrst, the structure f' $6E -)di~o~op5-tropic acid ester((-)tropoyl elerine, II) had been assumed,* nd thiscompound as synthesized ydrobromide .p. 174', a]f = -69' (o - 2; inwater); (Found: C, 55.6; H, 6.3r V, .8; Rr, 20.9. Cl$,,,04NRr equires C,52,5; , 6.3; J, .6; B, 20.7%~ and compared ith alkaloid U. Thesecompounds ere not identloel.

Feeding experimenta ith Z3(-) ropoyl alerlne (II) under the sameconditions s with dehydrohyoscyamine ed again to the formation fhyoscine, hile in the presence of cysteine it was converted nto thealkaloid U.

In contrast to intact branches of Dature ferox on Cyphomandre,homogenized cions thereof proved to be unable to carry out epoxidetioneither of hyoscyamine (I) or of dehydrohyoeayamine III). On the otherhand, sciona of Deture stramonium ., Daturs lnnoxie ILL,, Deture mete1 L.,Atrops beIladonne . grafted on Csphomandre nd fed with hyoscyamine nddehydrohyoscysmlne eave these compounds naffeoted.

No epoxidetion ook place when Dsture ferox on Cyphomsndra as fedeither with unesterified ropanols .g. tropine, tropenol, eloidine, rwith epoetropine; eocordlngly, he action of the oxidizing nzyme in playappears to be strongly stereospecific nd limited to the esters of 2 tropic

G G. Fodor, Leoture, Congress, 0thHungarian Chemists, udapest, syG. Janzsb. I. Koczor, A. Romelke.Kim. Folydirst 4, 296 (1958). _

nnivereery of the Society of16, 1958; . Fodor, P. Dcbb,J. T&h and I. Vincze, W,

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22 Epoxldation eqmimentr ofd~o~osq .ne

sold9 dth troplno, tropenol and jRr6R -tropandiol. However, mandelyl tropinehomatropine ir epoxldlaed in vlro; the optioal aotivlty of the new epow-tropanlum eater salt rtll l awaits invertigrtion to ahow whether the D orthe L mandelJ 1 eater (or both) 18 attaoked,

Our present working hypothesl8 for the lnteroonverrion of naturaltropane alkaloida In vlro may be deploted by the following sohemeI-DI I+II I -4v

I I I I

/ III dTr

9 S oonfiguration of (-) tropio sold haa been determlned reoentlyTy oorrelating with D (-) alanine b;r 0. Fodor and Cy. Ceepreghy,Tetrahedron Lettera No. 7, 16 (1959).

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Epoxidatlonxperimente f dehydrohyoscyamine 23

I , oateike auggeste for sUEslaid U th stmature of atropoyl-j$'@Q(-) dihydroxy ropene V), ege~3ing t ae ;L y-pm&at of hyoeclne orm-tion in the plant, nable o undergo poxidation,urther nveetigationeare in progress.