Natural product synthesis Vindoline

A systematic exploration of the intramolecular [4+2]/[3+2] cycloaddition cascade of 1,3,4-oxadiazoles was described. The studies permit the use of unsymmetrical dienophiles, dipolarophiles, and oxadiazoles as well as to control the cycloaddition regioselectivity and diastereoselectivity. The scope and utility of the reaction were defined <2006JA10589>. The tandem intramolecular [4+2]/[3+2] cycloaddition cascade reaction of 1,3,4-oxadiazole was applied to the syntheses of a series of natural products including a total synthesis of (-)- and ent-(+)-vindoline <2006JA10596>. 

Natural products have always been attractive targets for the application of newly developed synthetic strategies. In this field, only a few examples have been reported, in which intramolecular aryl radical addition reactions occur to non-activated carbon-carbon double bonds [69]. One of the early examples is the first total synthesis of (—)-y-lycorane [70]. More recently, formal total syntheses of aspidos-permidine [71] and vindoline [72] have been accomplished by an aryl radical... 

The use of Rh(II) catalysts for the formation of 1,3-dipoles from diazo compounds via rhodium-carbenoids has facilitated the use of the dipolar cycloaddition reaction in key steps in the preparation of natural products. The synthesis of aspidosperma alkaloids 227 and their derivatives is important because these alkaloids contain the highly functionalized vindoline nucleus which is found in... 

Murphy has investigated domino radical cyclizations of iodoaryl azides. This reaction found several applications in the total synthesis of natural product, as for instance Murphy s synthesis of aspidospermidine (Scheme 8.34), ° vindoline, horsfiline, and coerulescine. ... 

Further use of the modified Polonovski reaction has been made166 in the synthesis of four model vinblastine derivatives (271)—(274) from the vindoline relatives mentioned earlier 117 all four products have the natural stereochemistry at C-16. ... 

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