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 - Jan 1 2016 |
| Externally published | Yes |
Fingerprint
Keywords
- Biomimetic synthesis
- Dihydropyridine
- Indole alkaloid
- Multipotent intermediate
- Skeletal diversity
ASJC Scopus subject areas
- Organic Chemistry
Cite this
Development of an artificial assembly line generating skeletally diverse indole alkaloids inspired by biogenetic strategy. / Mizoguchi, Haruki; Oguri, Hiroki.
In: Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, Vol. 74, No. 9, 01.01.2016, p. 854-865.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Development of an artificial assembly line generating skeletally diverse indole alkaloids inspired by biogenetic strategy
AU - Mizoguchi, Haruki
AU - Oguri, Hiroki
PY - 2016/1/1
Y1 - 2016/1/1
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
UR - http://www.scopus.com/inward/record.url?scp=84992051165&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992051165&partnerID=8YFLogxK
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 -