Rhoeagenine diol

Scheme 87. Synthesis of rhoeagenine diol (438) and alpinigenine (441) from spirobenzyliso-quinolines. Reagents a, MsCl, Et3N b, OsOA c, HI04 d, NaBH4 e, lithium perhydro-%-boraphenalenyl hydride, THF f, Mn02.

Rhoeagenine diol (228) has also served to confirm the structure of the alkaloid 14-demethoxyrhoeadine (230).227 Treatment of (228) with 2M-HC1 for 2 hours on the steam bath gave a quantitative yield of (230). Further evidence for structure (230) was obtained by exhaustive Hofmann methylation and spectroscopic studies. On the basis of comparison of optical rotations for rhoeadine (223 R1 = R4 = Me, R2 + R3 = CH2) and 14-demethoxyrhoeadine (230), the contribution of the optically active centre at C(14) in the former was determined to be [a]l2 +396° (chloroform).227... 

Full details are now available from Irie s laboratory on the known conversion of appropriately substituted spirobenzylisoquinolines into rhoeagenine-diol ... 

The final stages of the synthesis, viz., conversion of rhoeagenine diol (C) to rhoeadine had already been accomplished during work on constitution of rhoeadine by F. Santavy, J. L. Kaul, L. Hruben, L. Dolejs, V. Hanus, K. Blaha and A. D. Cross, Coll. Czech. Chem. Commun., 30, 3479 (1965). 

The structure of rhoeagenine (I) suggested that oxidation might give rise to bicuculline or adlumidine (phthalideisoquinoline alkaloids) and that by subsequent correlation the absolute configuration of the rhoeadine and the isorhoeadine series, respectively, could be determined. Reduction would then afford the corresponding diols. However, oxidation and reduction afforded products (430) which did not correspond to phthalideisoquinoline derivatives (see Section III, K). 

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