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T H E SQUIBS IN51IIb 1L FUR hItUlCA1,
The Germine-Isogermine-Pseudogermine Isomerizations1 BY
s. MORRISKUPCHAN, MARYFIESER, c.R. NARAYANAN, LOUISF. FIESERAND JOSEF FRIbL) RECEIVEDJANUARY 18, 1955
Evidence is presented for partial structures IX, X and XI for germine, isogermine and pseudogermine, respcctivcly
Recent studies of the hypotensive principles of several V e r a t r ~ r n ~and - ~ Zygadenuse species have revealed that many of the most active compounds in this series are polyesters of germine. Germine, C27H&N, was first isolated by Poethke in 1937.' Extensive degradative studies have been reported by Jacobs and his collaborators during the past twelve years,s-10 and these studies recently have led to proposal of skeletal structure I for germine." I
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are attributable to an aldehyde group, and a band at 5.62 p is indicative of the y-lactone function. Furthermore, the substance forms an oxime ( m . p 27S279' dec., [ a I z 3 D $4' (c 1.47, alc.)). The constitution of this aldehydo- y-lactone offered the first experimental confirmation for the presence of an aketol-5-membered hemiketal system in a germine derivative. In a parallel experiment, Barton and Brooks obtained an analogous aldehydo- y-Iactonc by periodic acid oxidation of cevine orthoacetate. l 2 In September, 1953, Dr. R. B. Woodward kindly informed us of his deduction concerning the veraccvine-cevagenine-cevine isomerizations (V-VII) . .' , , , -, '
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Experimental support for the view that veraceviiic and cevine contain the same a-ketol-5-membercd Shortly before discontinuance of research on the hemiketal system and differ only in the configuraester alkaloids of germine a t the Squibb Institute,2 tion of the hydroxyl group of the a-keto1 system one of us (J. F.) found that germine acetonide hy- followed soon afterward.I4 The close analogy of drochlorides" (11) consumes one mole of potassium the germine-isogermine-pseudogermine isomerizaperiodate and affords a crystalline oxidation prod- tions to the veracevine-cevagenine-cevine isomeriuct which reduces Tollens reagent (m.p. 274-276' zations suggested similar structures in the two dec., [ a I z 34~2' ( c 1.54, alc.)). Further character- series. l59I6 ization of the substance a t Harvard showed it to be Pseudogermine was prepared by isomerization an aldehydo-y-lactone (111). of germine with sodium ethoxide in ethanol. (Isogermine likewise gave pseudogermine under thc A A A same conditions and this reaction completes the 0 0 0 analogy to the cevine series.) Pseudogermine acc€I()--l -+ 1) . e-II() tonide hydrochloride (IV), m.p. 283-284O dec., I1 0 --&I I IiC--O 11- L OkI prepared by the standard procedure,sa on oxidation , I with potassium periodate gave an aldehydo-y-lacTI I11 I \; tone I11 identical with that derived from germine Thus infrared alisorptiori bands at 3.ti.i and 5.79 p acetonide (11) (mixed m.p. and infrared spectral comparisons of aldehyde and oxime). The fact that ' 1 , I'reliminary accounts of t h i s work h a r e been reported in Communications t o THISJ O U R N A L , 76, 1200, 5259 (1954). T h e investigathe same aldehydo-y-lactone is formed from both -
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tion was supported by research grants from the National Heart I n s t i t i i t e , of t h e h'ational Institutes of Health, Public Eealth Service (H-15fi3 (C3)) a n d Research Corporation. ( 2 ) !a) J Fried. H. L. White and 0. Wintersteiner, Tms J O U K N A L , 72, 4 6 2 1 ( 1 9 , X ) ; (I,) J . Pried, P. Kumerof and K. hI. C o y , ibid., 74, :3(! 11 (Is:?). ( 3 ) M. E'.Klohs, c / al., ihi,i , 74, ISil, 4473 ( 1 9 5 2 ) . ( 4 ) G. S.M y e r s , \\'. L. Glen. r l ( I ] . , ibt,!., 74, 3198 (1962); .Yufurc, 170, 932 (1952). (,j)H. A. h-ash and R. AT. Brooker, THISJ O U R X A I . , 76, 1942 (1953). 16) S . A I . Kupchan a n d C. V. Delimala, ibid., 74, 3202 (19521; 7 6 , 5545 (1951); S. A I . Kupchan, C . V. Deliwala a n d R . D. Zonis, ibid.,77, 755 (1955). ( i ) TV. Poethke, A r c h Phur,itz., 276, 6il (1937). (8) I,. C. Craig and W. .4 Jacobs, J . Rir~i.i ' h e m . . (a) 148, 57 (1RL3); (1,) 1 4 9 , 4 5 1 (1943). (9) 11. Jaffe and W.A. Jacobs, i b i t i , , 193, 82.5 11'351) 110) S. \V. Pelletier a n d \\'. A . J a c o h i , Trrrs J O U K X A L . 76, 3248 I) (1!)53)
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Indzcsliy, 5 1 , (12) D. H. R. Barton a n d C. J. W Brooks, Chemislvy 1301; (1933); D. H. R. Barton, C. J. W. Brooks and J. S . Ipnwcctt, J . Chem. S n r . , 2137 (1954). ( 1 3 ) D. H . I
