TY - JOUR
T1 - Development of an artificial assembly line generating skeletally diverse indole alkaloids inspired by biogenetic strategy
AU - Mizoguchi, Haruki
AU - Oguri, Hiroki
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Biomimetic synthesis
KW - Dihydropyridine
KW - Indole alkaloid
KW - Multipotent intermediate
KW - Skeletal diversity
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U2 - 10.5059/yukigoseikyokaishi.74.854
DO - 10.5059/yukigoseikyokaishi.74.854
M3 - Review article
AN - SCOPUS:84992051165
VL - 74
SP - 854
EP - 865
JO - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
JF - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
SN - 0037-9980
IS - 9
ER -