Towards the Assembly of the Binary Vinca Alkaloids: Strategies for the Synthesis of Analogues of the Indole-Indoline Core of (+)- Vinblastine
Abstract
The clinically important alkaloids (+)-vinblastine (1) and (+)-vincristine (2) both exhibit extraordinary potency as anti-mitotic agents and act by destabilising polymerised tubulin. While the development of a structure-activity-relationship (SAR) profile around these natural products should allow for the identification of the relevant pharmacophore, this task is especially daunting because of the structural complexity of these compounds. Indeed, most analogues of the Vinca alkaloids are obtained through modifications of the natural products rather than being generated de novo by “total synthesis”...