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 also prepared by total synthesis including both enantiomers of vindorosine (4), minovine (31), 4-desacetoxy-6,7-dihydrovindorosine (32), and 4-desacetoxyvindorosine (48) as well as N-methylaspidospermidine (52). Subsequent extensions of the approach provided both enantiomers of dihydrovindoline (47), 4-desacetoxyvindoline (49), 4-desacetoxy-6,7-dihydrovindoline (50) and 4-desacetoxy-5-desethylvindoline (51).