Rhazinilam synthesis analogues

The tubulin-binding properties of (-)-rhazinilam were discovered through screening of a number of Malaysian plant extracts [60]. Natural (-)-rhazinilam induces tubulin spiralization, inhibiting tubulin assembly in the same way as vinblastine-like alkaloids, and protects microtubules from cold disassembly such as with paclitaxel [67]. This effect has never been observed with other microtubule poisons. For this reason, and despite the in vivo inactivity of (-)-rhazinilam [67], a number of analogues have been prepared by semi-synthesis and total synthesis (see Sections 3.1.3. and 3.2.3.) in order to improve the pharmacological properties of this molecule. 

Finally, one has to mention the work of Levy and co-workers who described the semi-synthesis of D-ring seco-rhazinilam analogues from (-)-tabersonine using an Emde degradation and /nCPBA oxidation [90]. The. veco-analogue 50 is only twice less active than rhazinilam on the inhibition of microtubules disassembly, illustrating that the absence of the D-ring is not strictly deleterious to the antitubulin activity [91,92]. 

Fig. (34). Synthesis of phenyl-pyrrole analogues of rhazinilam by Thai [92]...

Biphenyl-carbamate 164d, the most active analogue of rhazinilam to date, was taken as a lead and its synthesis was re-examined for the purpose of adaptation to the construction of a library of analogues, Fig. (36) [161]. 

Fig. (36). Synthesis of racemic biaryl-carbamate analogues of rhazinilam by Baudoin-Gueritte [161]...

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