Salamander alkaloids were found in the toxic secretion from Salamandra maculosa and atra L. by Zalesky in 1866. Samandarine was isolated as a main component of these alkaloids by Gessner and Cramer in 1930. Its structure has been proposed by Schopf and his colleagues through chemical, optical and X-ray crystallographic studies in 1960. The characteristic skeleton of samandarine containing the aza-oxa-bicyclo-octane system is common to four other alkaloids. The synthesis of pentacyclio nucleus of samandarine is described here. 1-Formyl-A-nor-5β-androst-1-en-17β-ol (XIV) was prepared from testosterone by a nine step sequence as described in the previous paper. The benzylamino Schiff base of XIV was reduced with NaBH_4 to give the unsaturated amine(XXVa). The formamide of XXVa was oxygenated with OsO_4 and resulting glycol (XXVI) was cleaved by Pb(OAc)_4 to give the seco-aldehyde (XXVIII). After selective protection of the aldehyde group as the ethylene-acetal (XXIX), carbonyl group at C-1 was reduced with NaBH_4 to give the epimeric amide alcohols (XXXa). Saponification of the formamide led to the epimeric α-amino alcohols (XXXb). Hydrolysis of ethyleneacetal with 75% acetic acid afforded two products in 45 and 38% yields after purification by silica gel 1pc. The former (XXXIa) was bicyclized compound and the latter was intramolecular hemiacetal. Removal of benzyl group of XXXIa with catalytic hydrogenation gave XXXIb, the hydroxyl isomer of samandarine, of which it and nmr spectra are very similar to those of the natural products.
