Idiospermine and idiospermamine

Of the calycanthaceous alkaloids identified to date, idiospermamine is the one that is closest biogenetically to idiospermine.

Idiospermamine can be envisaged as having been formed by coupling of a calycanthine moiety (through a C ortho to a tetrahydroquinoline N, ie C8) at the beta position of the indole ring of an N-methyltryptamine molecule followed by the formation of a pyrrolidine ring through the linking of the tetrahydroquinoline N to the alpha position of the N-methyltryptamine molecule and methylation of the N of the indole ring.

Idiospermine, on the other hand, can be envisaged as having been formed by the coupling of a calycanthine moiety (through a C para to a tetrahydroquinoline N, ie C6) at the beta position of the indole ring of an N-methyltryptamine molecule followed by aryl migration of the calycanthine moiety and concerted methylation of the N of the indole ring followed by loss of H+ to effect aromatization of the indole ring (This may be regarded as analogous to the coupling in the formation of hodgkinsine and the quadrigemines which are followed by N-methylation, aryl migration and aromatization.).

I envisage the following related alkaloid might also one day be identified:

Coupling of a calycanthine moiety (through a C ortho to a tetrahydroquinoline N, ie C8) at the beta position of the indole ring of an N-methyltryptamine molecule followed by aryl migration of the calycanthine moiety and concerted methylation of the N of the indole ring followed by loss of H+ to effect aromatization of the indole ring. This alkaloid might be termed idiospermine-B.

Idiospermuline and idiospermamine – other tryptamine trimers from Idiospermum australiense

In an earlier post reference was made to both idiospermuline and idiospermamine.

Idiospermuline was isolated from the seeds of Idiospermum australiense by researchers from the Department of Pharmacology of the University of Sydney (Rujee K. Duke, Robin D. Allan, Graham A. R. Johnston, Kenneth N. Mewett and Ann D. Mitrovic, “Idiospermuline, a trimeric pyrrolidinoindoline alkaloid from the seed of Idiospermum australiense, Journal of Natural Products, vol. 58 (1995), pp1200-1208).

(-)-Idiospermuline was isolated form the seeds of the plant together with (+)-calycanthine and (-)-chimonanthine. Idiospermuline is a chimonanthine derivative and may be viewed as consisting of a chimonanthine moiety coupled via its C7’ carbon atom to the C3a” carbon atom of a pyrrolidinoindole moiety. In overall terms it is formally a dimethylated derivative of hodgkinsine, an alkaloid from Hodgkinsonia frutescens F. Muell (Rubiaceae) – A.A. Gorman, M. Hesse, H. Schmidt, P.G. Waser and W.H. Hopff in The Alkaloids, vol. 1, p203 (The Chemical Society: London 1971). Hogkinsine is also isolated from Psychotria sp.

The Overman group have made an enantioselective synthesis of (-)-idiospermuline (Tetrahedron, vol. 59 (2003), pp6905-6919).

Idiospermuline (C35H42N6) has only one secondary nitrogen atom and has a molecular weight of 546.

Idiospermamine B, on the other hand (C34H38N6, see an earlier post) has two secondary nitrogen atoms.

J.B. Bremner has reported two new alkaloids from Psychotria malayana Jack (Surya Hadi and John B. Bremner, Initial Studies on Alkaloids from Lombok Medicinal Plants, Molecules, vol. 6 (2001), pp117-129). From the plant Bremner and his colleague isolated hodgkinsine (C33H38N6, M.W. 518), chimonanthine and two other alkaloids with molecular weights of 186 and 574.

I wonder if it is possible that the alkaloid with M.W. of 574 isolated by Bremner is a trimethylated derivative of idiospermine (C34H40N6)?