Autumnaline

The Lily botanical family (Liliaceae Adans., Juss.) (Table 14) is spread worldwide and contains more than 200 genera and around 3500 species. Some genera of this family produce L-tyrosine-derived alkaloids. The genus Kreysigia yields autumnaline, floramultine and kreysigine. 

From L-tyrosine, and alternatively also from L-phenylalanine, kreysigine synthesis begins with dopamine (Figure 36). -autumnaline is derived via a Mannich-like reaction. 5 -autumnaline is converted into floramultine by the oxidative coupling. Subsequently, the kreysigine is synthesized through the... 

These alkaloids have a phenyl or phenylpropyl nucleus. The group includes simple phenyl amine (tyramine, hordenine), catecholamine (dopamine, noradrenaline, adrenaline), simple tetrahydroisoquinoline (mescaline, anhalamine, anhalonine, anhalonidine), benzylisoquinoline (e.g., papaverine), phthalideiso-quinoline (e.g., noscapine), phenethylisoquinoline (autumnaline, floramultine and kreysigine), tetrahydroisoquinoline (emehne and cephaeline) and terpenoid tetrahydroisoquinoline (secologanin and ipecoside) alkaloids. 

Several genera in the lily family (Liliaceae) are found to synthesize analogues of the benzylte-trahydroisoquinoline alkaloids, e.g. autumnaline... 

The structure of autumnaline has been confirmed by an X-ray crystallographic study of 3-methyl-7-0-benzylautumnaline (30).41 Autumnaline itself has been isolated from Colchicum latifolium.42... 

The diphenolic isoquinoline (10), C21H27NO5, was obtained together with the known isomeric base (-)-autumnaline (11). The H-NMR spectrum of 10 differed from that of 11 only by a slight shift of the H-5 and H-8 absorptions. This indicated that the isomerism resided in ring A, more specifically in the relative positions of the methoxy and hydroxy substituents. Complete NOE studies of 10 and 11 conclusively established the substitution pattern in rings A and C in each case (4). 

The simple phenethylisoquinoline alkaloid autumnaline (68), isolated from Colchicum cornigerum (2), has the basic skeleton of several phenethylisoquinoline alkaloids described later. The structure of 68 was arrived at through comparison with a synthetic sample (2a, 2b). 

Definitive evidence arising from and H-labelling studies points to the intermediacy of (5)-autumnaline (124) in the biosynthesis of colchicine (125). The incorporation of (i S)-[l- C]autumnaline [as (124)] into colchicine (125), with enhancement of the n.m.r. signal for C-7 only, affirms this conclusion. 

Nasreen, A., M. Rueffer, and M.H. Zenk (1996). Cytochrome P-450-dependent formation of isoan-drocymbine from autumnaline in colchicine biosynthesis. Tetrahedron Lett. 37, 8161-8164. 

Simple Phenethylisoquinolines.—The alkaloid (—)-autumnaline (210) from Colchicum cornigerum (Liliaceae, subfamily Wurmbaeoidae) possesses the absolute configuration shown, and its synthesis has been carried out. ... 

Androcymbine Analogues and the Homomorphines.—C. cornigerum possesses a variety of new alkaloids derived from autumnaline among which are CC-10 (211), CC-20 (212), CC-2 (213), whose structure was proven by X-ray analysis of its 0-acetyl methiodide, CC-3b (214), and (—)-kreysiginine (216). ... 

Eucomnalin is identical with the former autumnalin (65), a name which had already been conferred on an alkaloid from Colchicum autummle L. 

SiDWELL, W. T. L., and Ch. Tamm The Homo-Isoflavones II Isolation and Structure of 4 -0-Methylpunctatin, Autumnalin and 3,9-Dihydroautumnalin. Tetrahedron Letters 1970, 475. 

Alkaloids are not limited to those natural products which are basic in character. For example, colchicine isolated from Colchicum autumnale (Ldiaceae) and used for the treatment of gout, etc. is not basic because the nitrogen atom in the molecule is present in a neutral amide group. However, the biosynthetic precursor of colchicine is autumnaline, a typical, basic phenethylisoquinoline alkaloid. Therefore any compound derived from such an intermediate should be classified as an alkaloid. 

Using this type of chemical classification is useful, and such a classification is used predominantly in this book. However, this approach also encounters some challenges. For example, autumnaline and (S)-reticuline are typical isoquinoline alkaloids, whereas colchicine and morphine, which... 

The system recently used is to classify the alkaloids based on their biosynthetic origins [1]. According to this approach, it is appropriate to discuss autumnaline and colchicine, and (S)-reticuhne and morphine in the same section based on a common amino acid precursor. Similarly, (—)-hyoscyamine and scopolamine isolated from Scopolia sp. (Solanaceae) can be discussed in the same section with cocaine isolated from Erythroxylon (Erythroxylaceae). 

Autumnaline is a phenethylisoquinoline alkaloid, and possesses an additional Cj unit compared with the benzylisoquinoline alkaloids. Autumnaline, postulated to be the biosynthetic precursor of colchicine, was isolated from Colchicum cornigerutn (Colchicaceae) [4]. O-methylandrocymbine is formed through the intramolecular -oxidative phenolic coupling... 

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