17%
HAROLD CONKOY ~CUXTRI€lUlIoN FROM
Picrotoxin.
THE
DEPARTMEST O F CHEMISTRY
01)HriAXLlEIS
UNIVERSI 1.Y]
a-Picrotoxininic and Bromopicrotoxininic Acids ; Apopicrotoxininic Dilactone
111.
BY HAROLD CONROY RECEIVED J U L Y 30, 1956 Arguments are presented allowing delineation of the structures of the a-picrotosininic arid broinopicrotoxiiiinic acids, long known as degradation products of picrotoxinin. Evidence for their formulation as complex glycidic acids is drawn primarily from several remarkable transformations yielding the new derivatives designated a s diliydro-P-bromopicrotoxiiiinic acid and as apopicrotoxininic dilactone.
Although the structures of several important simpler degradation products of picrotoxinin have been elucidated, these have been formed in reactions sufficiently complex or drastic t o make dubious any detailed structural correlation with the parent compound. The fundamental relationships among picrotoxinin, its bromination products and the picrotoxininic and bromopicrotoxininic acids as set forth in the figure were first studied by Meyer and Bruger2 and by H ~ r r m a n n . Adduc~ tion of structure proof for these more intimately related but more complicated substances, and as well of picrotoxic acid,4 Schlittler’s “compound C”j and neopicrotoxinin,6is still desired.’
acid8; (b) the alkaline cleavage productsg (I1 and 111); and (c) picrotoxinide’ (IV), the product of pyrolysis of dihydro-a-picrotoxininic acid. The evidence for the functional groups present in picro-
HooCmoH d
j$
o”r”co::A HO
o
lV
toxinin suggests that from the skeleton (I) must be constructed two lactone systems, one hydroxyl picrotoxinin, CisHlsOs group and one ether linkage. The hydroxyl group B r 2 if Zn appears to be tertiary, for picrotoxinin cannot be acetylated by usual procedures, nor can it be oxia-broino~icrotoxinin,ClsHijOsBr 8-hrornopicrotoxinin, CI5Hi5O6Br dized to any corresponding ketone; moreover this tertiary hydroxyl must be located within bonding OH,)OHdistance of the isopropenyl group of I, because it and is no longer participates in a-bromopicrotoxiuinic B-broinopicrotoxininic acid CIsH170;Br,monobasic acid CLsHI7O7Br, monobasic present in the bromopicrotoxinins. l 1 The skeletori (I) contains two oxygens (i.e., a t C-6 and (2-13) which might qualify as the hydroxyl, and that a t C-6 could well, configurations permitting, be exa-picrotoxiriiriic acid, ClbH180,, monobasic-pected to bridge to the double bond on brominaI Hz Hfl tion. The mechanism of the consecutive dealdodihydro-a-picrotoxininic acid, P-picrotoxininic acid, lizations’ leading to the formation of the Schlittlcr ClaHpoO,, monobasic C15H180:, monobasic cleavage products (I1 and 111)9requires that the C-6 oxygen be not bound in a stable oxide bridge in \Ye have drawn the carbon-oxygen framework the compounds which do undergo the cleavage, and ( I ) ’ from three sets of degradation products: (a) F..4ngelico, Goza c h i m . ilal , 41, i i , 337 (1911); A . Oglialoro, picrotic acid, picrotonol and hydroxynorpicrotic i b i (8) d . , 21, ii, 213 (1891); J . C. Warlandand A . Robertson, J . C h e m Sor ,
4
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037 (1939); D . Mercer. A Rohertson and K S . Cahn, ibid., !I87 (1935). (9) 51. Sutter anti E . Schlittler, Hell,. Lliiiit. A d a , SO, 403 (1947); i b i d . , 30, 2102 (1947), ibid., 32, 1863 (1949); ibid.,32, 18FO (10491 (10) R. XV. H . O’Donnel. A . Robertson and J . C . Harland, J . Chriiz. S O L . ,1261 (19391. ( 1 1) T h e bromopicrotoxinins contain a n e x 8-bromoetlier linkage. T h e fact t h a t two compounds are formed was interpreted on t h c basis t h a t a new asytnnietric renter is introduced:
11) T h e previous articles in this series appear iu T H I S JOURIAI., 7 4 , 4!)1 (1052); 74, 3046 (1952). 12) R. J . I\Ieyer and P. Bruger, B e y . , 31, 2985 (1898). ( 3 ) P. Horrmann, ibid., 46, 2090 (1912); 4 6 , 2793 (1913). An alternative crpl:tn;ition n o u l i l Ibe that one of the Iironio d e r i \ , I (4) P. Horrmann, A m . , 411, 273 (1916). t i v e s is formed as given a l m v c vbile the other ari.es Iron1 a d d i t l o l l i n ( 5 ) M Sutter and E. Schlittler, H e l v . Chiin. Aclu, 33, 902 (l!)50). t h e reverse sense, as shrjwn: (6) D. Mercer and A. Robertson, J . C h e m S u c . , 288 (19SG); S . S. Slater, ibid., 806 (1949); S. IT.Slater a n d A . T. Wilson, X a t i r v c , 1 6 7 , 324 (1951). (7) I n a brief preliminary report [H. Conroy, THISJ O U R X A L , 73, 1889 ( 1 9 5 1 ) ] structures for picrotoxinin, a-picrotoxininic acid and picrotoxic acid were proposed on t h e basis of t h e very limited evit i r i i w t h i i i : L \ uil:LIBIt, ‘I‘hc j>r(il>li.iiii01 llir i t r i i r t i i r r q of ~ > i r r o t i i ~ i i i i i i J I ~ < 1I t t r 1 u l t , u < . :t
