Abstract
With intention to formulate a potentially general synthetic strategy generating a collection of skeletally diverse scaffolds without simplifying a structural feature of natural products, we devised an artificial assembly line of terpenoid indole alkaloids and its variants. Inspired by the key biosynthetic intermediate, dehydrosecodine, responsible for divergent intramolecular cyclizations, a "multipotent intermediate" with improved stability and versatile reactivity was designed to establish a streamlined divergent synthetic process. A newly developed copper-catalyzed cyclization protocol allowed rapid formation of the sensitive dihydropyridine system. By harnessing the versatile reactivity of the multipotent intermediate, three types of bioinspired [4+2] cycloadditions as well as two types of oxidation-triggered cyclizations were successfully implemented to generate five distinct scaffolds involving iboga-, aspidosperma-, and ranginine- and ngouniensine-type skeletons and unnatural tetracyclic framework within 6-9 steps from tryptamine. Furthermore, simple manipulations of the [4+2] products allowed total synthesis of (-)-catharanthine, (±)-vincadifformine and (±)-andranginine, demonstrating a structural relevance of our compound collections to the natural products.
Original language | English |
---|---|
Pages (from-to) | 854-865 |
Number of pages | 12 |
Journal | Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry |
Volume | 74 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2016 |
Externally published | Yes |
Keywords
- Biomimetic synthesis
- Dihydropyridine
- Indole alkaloid
- Multipotent intermediate
- Skeletal diversity
ASJC Scopus subject areas
- Organic Chemistry