Stemofoline structure

Stemofoline is an insecticidal alkaloid produced in the leaves and stems of the plant Stemona japonica. It has a good spectrum of activity, with rapid action, and is a potent agonist of the nicotinic acetylcholine receptor in insects. These features make it a promising lead, except that its highly complex polycyclic structure is a real challenge for synthesis (Figure 3). 

Stemona alkaloids. Root extracts of the medicinal plants Stemona japonica and S. tuberosa (Stemona-ceae) have been used in Chinese and Japanese folk medicine as insecticides, anthelmintics, and as drugs for the treatment of tuberculosis, bronchitis and pertussis. Responsible for the activities is a group of more than 20 polycyclic alkaloids with diverse structures, e.g. protostemonine CjsHsiNOj, Mr 417.50, mp. 172-173 °C, [alD +148° (CH3OH) and stemofoline. 

The stemofoline group comprises some of the structurally more complex representatives of the Stemona alkaloids, and currently ten alkaloids have been described stemofoline (48) 17,22,53,54), oxystemofoline (49) (77), methoxystemofline (50) (77), 2 -hydroxystemofoline (51) 22,36), 16,17-didehydro-16( )-stemofoline (52) 22,54), also named as didehydrostemofoline, l, 2 -didehydrostemofoline or asparagamine A (5,55),... 

The structure of (115, 12i )-dihydrostemofoline (56) was established by high resolution mass spectrometry (which indicated it to be a stemofoline derivative) and by NMR spectroscopy, where two additional signals at S 3.79 and 4.60 ppm were observed in comparison to stemofoline (48). The cis configuration of Hll and the methyl group at CIO followed from NOESY experiments, and the 115,127 configuration was assigned by comparison with the spectroscopic data available for the syn hydrogenation derivative of stemofoline (48) (56). 

The first alkaloid to be reported was stemocurtisine (58), isolated from the roots of 5. curtisii, the structure of which was established by X-ray crystallography. The piperidine ring adopts a chair-hke conformation, and it displays an ether bridge involving Cl and C9. The acetal-like nature of C9 is confirmed by the presence of a signal at 120.5 ppm in its C-NMR spectrum. The absolute configuration is not known, but it is assumed to be the same as the one in those alkaloids with the same C/D ring substructure [stemofoline (48)] (57). The same alkaloid was also isolated from the roots of Stemona sp. (56). 

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