A concise 11-step total synthesis of (-)- and ent-(+)-vindoline ( 3) is detailed based on a unique tandem intramolecular [ 4 + 2]/[ 3 + 2] cycloaddition cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which three rings and four C-C bonds are formed central to the characteristic pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. As key elements of the scope and stereochemical features of the reaction were defined, a series of related natural products of increasing complexity were prepared by total synthesis including both enantiomers of minovine ( 4), 4-desacetoxy- 6,7-dihydrovindorosine ( 5), 4-desacetoxyvindorosine ( 6), and vindorosine ( 7) as well as N-methylaspidospermidine ( 11). Subsequent extensions of the approach provided both enantiomers of 6,7-dihydrovindoline ( 8), 4-desacetoxyvindoline ( 9), and 4-desacetoxy- 6,7-dihydrovindoline (10).