Rhazinilam-type compounds

ABSTRACT Numerous molecules containing a biaryl unit have been found in Nature. Many of them exhibit a variety of biological actions. In this review, we will focus only on natural bridged biaryls that possess axial chirality and exhibit antimitotic activities. Thus, we will first present the occurrence and structure of three families of natural compounds that display these particular structural and biological features the allocolchicinoids, steganes and rhazinilam-type compounds. We will then describe the semi-synthetic and synthetic approaches to biaryls belonging to these three series. Their interaction with tubulin, a heterodimeric protein that is critical for the formation of microtubules and consequently of the mitotic spindle, will be discussed. 

In the three different approaches envisaged for the total syntheses of rhazinilam, the construction of the pyrrole ring was operated in two different manners a Knorr-type reaction in the Smith synthesis and a 1,5-electrocyclization of an allyl-iminium compound in the Sames and Magnus syntheses. 

It is of interest to compare the alkaloidal composition of the Indonesian L eugenefolia which gave besides leuconolam, 21-O-methylleuconolam and rhazinilam-N-oxide, yohimbine, P-yohimbine, and the diazaspiroleuconolam compound, leuconoxine (17S) [136], which has since then also been obtained from the North Borneo species, Kopsia tenuis [19], A similar diazaspiroleuconolam derivative 176 has been obtained via a facile acid-induced ring-reclosure reaction of leuconolam, while the base-induced reaction gave the meloscine-type derivative 177 [127,128]. 

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