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Trifluoroacetic acid treatment of p-quinol acetates derived from phenethylisoquinolines has led to the formation of (±)-homoaporphines, (±)-homomorphinandienones, and (±)-homoproaporphines. Thus three new (±)-homoaporphines (10g–i) possessing a hydroxy group in ring D have been synthesized. The stereostructure of (±)-homoproaporphine (4b), formed as a single spiro-isomer, has been determined by means of X-ray crystallographic analysis, partly for the settlement of stereochemistry on isomeric natural kreysiginone. On the basis of the above result, the steric course for the formation of (4b) has been discussed. An efficient method, consisting of oxidation with lead tetra-acetate of phenethylisoquinolines in trifluoroacetic acid–acetic acid, for the predominant formation of (±)-homomorphinandienones, has been newly developed.

Photolysis of 1-(2-bromo-4-hydroxy-3,5-dimethoxyphenethyl)-1,2,3,4-tetrahydro-7-hydroxy-6-methoxy-2-methylisoquinoline (8) in the presence of sodium iodide gave (±)-androcymbine (1). When the photolysis was done without sodium iodide, it afforded only multifloramine (10).

The thermal decomposition of the diazonium salt, derived from 1-(2-amino-3, 4, 5-trimethoxybenzyl) -1, 2, 3, 4-tetrahydro-6, 7-dimethoxy-2-methylisoquinoline (XI) which was prepared by an usual method, by our method gave the morphinandienone type compound (C-nor-androcymbine) (X). This paper also described the approaches to the synthesis of androcymbine (I).

The structure and absolute stereochemistry of androcymbine (3) are proved by spectroscopic study and by reductive cleavage of its O-methyl ether to a 1-phenethylisoquinoline, which is synthesised. Emphasis is given (a) to the importance of O-methylandrocymbine in relation to colchicine biosynthesis and (b) to the status of androcymbine as the forerunner of a new class of 1-phenethylisoquinoline alkaloids.

Publisher Summary Phenethylisoquinoline alkaloids—simple 1-phenethylisoquinoline, homomorphinandienone, bisphenethylisoquinoline, homoproaporphine, homoaporphine, and homoerythrina alkaloids—are related to the benzylisoquinoline alkaloids, such as morphinandienone, bisbenzylisoquinoline, proaporphine, aporphine, and erythrina alkaloids. The phenethylisoquinoline alkaloids share a common origin from the 1-phenethylisoquinoline precursor, and their biosyntheses parallel the formation of analogous alkaloids from 1-benzylisoquinoline. Among these, the notable alkaloids are the simple 1-phenethylisoquinoline and homomorphinandienones, which are key intermediates in the intriguing problem of the biosynthesis of colchicine. The other phenethylisoquinolines, however, do not have a close structural resemblance to cholchicine. Phenethylisoquinoline alkaloids have been isolated from six genera— Androcymbium , Colchicum , Kreysigia , Bulbocodium , Schelhammera , and Phelline . Except for Phelline , whose family affiliation is still in question, these genera are all Liliaceae. These alkaloids have been listed in this chapter along with their physical properties. The chapter discusses their structures, the various chemical reactions they are involved in, and the stereochemistry. The chapter describes homomorphinandienone and its analogs, bisphenethylisoquinoline, homoproaporphine, homoaporphine, and homoerythrina alkaloids. Androcymbine and salutaridine have a mirror image optical rotatory curve.

The aerial parts of ANDROCYMBIUM MELANTHIOIDES yielded known alkaloids cornigerine, colchicine, N-formyl- N-deacetylcolchicine, 2-demethylcolchicine, 3-demethylcolchicine, demecolcine, 2-demethyldemecolcine, 3-demethyldemecolcine, beta-lumicornigerine, beta-lumicolchicine, gamma-lumicolchicine, androcymbine, O-methylandrocymbine, and melanthioidine. Of these, O-methylandrocymbine and beta-lumicornigerine are reported for the first, time. The alkaloid, formerly designated as compound AM-3, has been identified as N-deacetyl- N-dimethyl-gamma-lumicornigerine 1. Its spectral data are given.

The diazotisation of 6,7-dimethyoxy- and 7-benzyloxy-6-methoxy-1-(2-amino-4,5-dimethoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline (VIII) and (XXI), followed by decomposition of the resulting diazonium salts, gave demethoxy-O-methylandrocymbine (VII), whose structure has been assigned by spectroscopic methods. The syntheses of the aminoisoquinolines (VIII) and (XXI) are also described.

Phenolic oxidative coupling of 1,2,3,4-tetrahydro-7-hydroxy-1-(3-hydroxy-4-methoxyphenethyl)-6-methoxy-2-methylisoquinoline (VIII) with potassium fericyanide afforded a homomorphinandienone-type compound (IX), which was methylated with diazomethane to give demethyl-O-methylandrocymbine (X), identical with an authentic sample obtained by a modified Pschorr reaction.