Erythrinanes

Reactions of 3- and 4-piperidone-derived enamines with a dienester gave intermediates which could be dehydrogenated to tetrahydroquinolines and tetrahydroisoquinolines (678). The methyl vinyl ketone annelation of pyrrolines was extended to an erythrinan synthesis (679). Perhydrophenan-threnones were obtained from 1-acetylcyclohexene and pyrrolidinocyclo-hexene (680) or alternatively from Birch reduction and cyclization of a 2-pyridyl ethyl ketone intermediate, which was formed by alkylation of an enamine with a 2-vinylpyridine (681). 

Tanaka, H., Etoh, H., Shimizu, H., Oh-Uchi, T., Terada, Y. and Tateishi, Y. 2001. Erythrinan alkaloids and isoflavonoids from Erythrina poeppigiana. Planta Medica, 67 871-873. 

Scheme 1. Disfavored 5-endo-trig radical cyclization and application to erythrinane framework...

In the Erythrina series, the total synthesis of ( )-erysotramidine (10), an oxo-erythrinan alkaloid, isolated from Erythrina arborescens Roxb.,13 has been... 

Several c/s-erythrinan derivatives have been synthesized in Mondon s laboratories 17 e.g., the cycloerythrinane (16a) was obtained by heating the bromo-compound (15) with potassium hydroxide in diethylene glycol at 180 °C. On hydrolysis, it yielded the keto-amide (16b), which afforded the amide (16c) and the amine (16d) via the unsaturated amide (17). Bromination of the ketone... 

Toda, J., Niimura, Y., Takeda, K., Sano, T., and Tsuda, Y. (1998) General method for synthesis of erythrinan and homo-erythrinan alkaloids (1) synthesis of a cycloerythrinan, as a key intermediate to erythrina alkaloids, by Pummerer-type reaction. Chemical e[ Pharmaceutical Bulletin, 46, 906-912, and literature cited therein. 

Another approach to the erythrinan skeleton has been developed (Scheme 3).11 The hexahydro-indolone (23), readily available from indoline (21) via the imino-enol ether (22), underwent cyclization [in very low yield (4%)] on treatment with phosphorus oxychloride to give the erythrinan derivative (24). Uncyclized compound (25) was identified as a by-product (16%) in this reaction. This latter compound was formed in 47% yield, with no product (24), when the cyclization was attempted in chloroform solution. Extensive variation of reaction conditions failed to give reasonable yields of the required compound (24). 

A detailed study of the Pummerer reaction of a series of A(-alkenyl-a-sulfinylacetamides has shown that, depending upon the number and position of methyl groups on the double bond, five- or six-mem-bered ring lactams are obtained. This reaction has been applied to a concise synthesis of the erythrinane... 

During the course of attempts to synthesize unsaturated derivatives of erythrinane Mondon and Menz (2) found an unexpected ring closure of VIII to form a seven-membered ring. The product (IX) could readily be converted to apoerysopine as shown in Fig. 2. Several of the intermediates in the conversion of VIII to IX could be isolated using milder conditions. 

A completely different route devised by Prelog and co-workers (14) not only afforded a new synthesis of the erythrinane skeleton but also achieved a method of introducing an oxygen function at C-3, the site of the aliphatic methoxyl in the alkaloids. The synthesis is outlined in Fig. 5. The dihydroisoquinolinium salt XXXIV was prepared by Bischler-Napieralski ring closure of the lactam XXXIII. Hydrolysis of the vinyl chloride of XXXIV gave the methyl ketone XXXV. When this salt was made alkaline, addition of the carbanion from the acidic methyl to the C=N double bond created the spiro link. Sodium borohydride reduction of XXXVI gave a mixture of epimeric alcohols. One of them had an IR-spectrum identical with that of a transformation product (XXXVII) of erysonine (If) and on resolution w ith tartaric acid its (— )-enantiomer proved to be identical with XXXVII. 

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