Ipecoside structure

Finally, X-ray crystallographic analysis of 0,0-dimethylipecoside (143), together with the knowledge that hydrolysis of ipecoside (19) produces D-glucose, has established its structure and absolute stereochemistry (7/5). The position of the double bond in the ( )-unsaturated lactam acid 144, a synthetic intermediate for the emetine precursor ( )-45, has been inferred from chemical and spectroscopic evidence (285) and confirmed by an X-ray study (286). 

A clue to the structure of ipecoside was obtained from the NMR and mass spectra of the glycoalkaloid and many of its derivatives. The NMR spectrum of ipecoside hexatrimethylsilyl ether showed the presence of two aromatic protons, four olefinic protons, one methoxycarbonyl, and one N-acetyl function. In the mass spectrum of ipecoside no molecular ion could be detected, but important characteristic peaks appeared at m/e 220,206,178, 164, and 43, assigned to the cleavage pattern of substituted IV-acetyl-l-alkyl-l,2,3,4-tetrahydroisoquinolines. 

The structure assigned to ipecoside (2) has been confirmed by partial synthesis. Dopamine (21), on condensation with secologanin (22) at pH 5.0, afforded a mixture of deacetylipecoside (23) and deacetylisoipecoside (24) separated by countercurrent distribution. There was a preponderance of the 5j3 isomer in the reaction. Acetylation of deacetylipecoside followed by Zemplen O-deacetylation furnished ipecoside identical with the, natural material (14). 

As a result of biosynthetic studies on the monoterpenoid indole alkaloids, which in particular established loganin as the key intermediate, it was predicted that the crucial protoalkaloid should be 35 (undefined stereochemistry) formed from the hypothetical secologanin and tryptamine (2 7). This argument received support from the structures of ipecoside (vide supra) and cordifoline (vide infra). Subsequently, secologanin was discovered... 

Third, the X-ray structure determination of 0,0-dimethylipecoside established the stereochemistry of H-5 in ipecoside as /8 rather than a as a consequence of the correlation via molecular rotation differences, the corresponding H-3 in vincoside must have the /8 configuration (13). 

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