THESTRUCTURE OF GALANTHINE
hug. 20, 1956 [CONTRIBUTION FROM
THE
-Llejl
LABORATORY OF CHEMISTRY OF NATURAL PRODUCTS, KATIOSALHEART I ~ s i rIJiI C , N A II O U L INSTITUTES O F HEALTH]
Alkaloids of the Amaryllidaceae. M. On the Structure of Galanthinel BY H. >I. FALES ASD W.C. T \ 7 ~ ~ ~ ~ ~
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RECEIVED RIARCH 21, 1956 The ring system and functional groups of the alkaloid galanthilie h a l e beeii deteririiiitd It kid5 beeii i h o i ~ t itli'it t l i ~ aliphatic methoxyl group of galanthine is located in the 2-position I t is suggested t h a t the alkaloid possesiei the structure Ia
Galanthine was isolated by Proskurnina and has been found in the pyrolysis of g,tlaiitliiiic. Areshkina from the Caucasian snowdrop (Galan- IVhen galanthine was heated above its inelting thus zloronowii Losinsk.) in 1947.2 Characterized point in vacuo, aromatization of ring C occurred to by its analysis and the analysis of the chloride, form 11. The product was identical with that ohbromide and perchlorate salts, the base was as- tained by a similar treatment of niethylpseudolysigned the molecular formula C16H2aN04. Galan- corine (Ib) thine was reported t o contain three methoxyl OR OK groups and one hydroxyl group, although no proof of the latter was offered. More recently galanthine has been isolated from several of the garden varieties of -Varcissus pseudonarcissus L. l v 3 These isolation and characterization studies confirmed the revised formula CI8H&04 for galanthine which had been presented by Proskurnina.4 While galanthine (like lycorine) appears to undergo the I11 I Hofmann and Emde degradations with the formation of a second aromatic ring,2,4110 chemical proof of the double bond or a hydroxyl group has been given although such groups usually are present in ring C if aromatization occurs. In this paper we wish t o prove the presence of these groups. From oxidative degradations we have been able to assign a position t o the aliphatic inethoxyl group and derive a tentative structural formula (Ia) for the alkaI1 loid. 0E1 The presence of both a hydroxyl group and a double bond in galanthine was shown by the formation of a dihydromonoacetylgalanthine when galanthine was hydrogenated in glacial acetic acid arid perchloric acid using platinum oxide catalyst. In the absence of perchloric acid, dihydrogalaiithine was formed. JiTith this information, the functional groups of galanthine suggested by Proskurnina I \\have been demonstrated experimentally. Formula Ia with the positions of the double When an ethanolic solution of galanthine was bond, hydroxyl and aliphatic methoxyl unassigned oxidized with selenium dioxide, a quaternary base was suggested for galanthine b y P r o ~ k u r n i n a . ~was obtained. Characterized as its nitrate and 'The parent ring systeni, as well as the location of perchlorate salts, the alkaloidal moiety possessed the two aromatic methoxyl groups, was indicated the molecular formula C18H18S03~+ and coiitained in two ways. Enide degradation of lycorine (117) three riiethoxyl groups. In contrast to the oxidaand subsequent ether cleavage gave a base (1Tb) tion products of lycorinee and inethylpseudolywhich was identical with the material derived from corine,l no free betaine was obtained upon gradual galanthine in a similar manner.4 Furthermore, it basification of a solution of the nitrate salt. Inseems likely that the Emde base Va from galan- stead, the nitrate of IIIa was precipitated from S O ~ U thine is identical with the product from methyla- tion, presumably by a salting-out process. In :tcitl tion of Vb derived from the Eriide degradation of solution the ultraviolet absorptioii spectrum of l y c o r i i i ~ . ~-inalternative proof of the ring systeni IIIa was nearly identical with that of I I I b . ' 111 and the position of the aromatic methoxyl groups basic solution I I I b showed a drastic change i t 1 the positions of its maxima due to betaine forination. ( 1 ) Paper VIII, H. XI. Fales, Laura D. Giuffrida and XV. C . Wild;is expected, the maxima of the methyl ether IIIa man, THISJOURNAL, 78, 4148 (1956). did not change in wave length in basic solution. (2) N. F. Proskurnina and L. P a . Areshkina. Zhzir.. Obshckei Rhiiit., 17, 1216 11947). .I slight diminution of extinction coefficients was (3) 1 i .r.. RI,IL stld I{. I,bmkr, f h c r u . R e v , , ~ - ~ l ) s e t - ~ 'Thr. ~ c l . iiltravicilct sprctr:i rif sytiflirtic~ fl) Pi. I;. l ' r n i k u m i n i . l h b l , t d . , ~1 I-mi ,A',,,
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