Systematic production of skeletally diverse alkaloids exploiting a multipotent intermediate

Research Press Release | January 07, 2014

Press Release
Key Points

・Inspired by divergent biosynthetic route to valuable molecules produced by plants, an artificial assembly line generating skeletally diverse alkaloids without structural simplification of natural products composed of multicyclic skeleton has been successfully developed.

・This research could provide a foundation for cost-effective production of untapped medicinal resources with higher hit rates and lower probabilities of side effects.

・An innovative synthetic strategy not only enables flexible alteration of functional group properties, important for the biological activities, but also allows systematic diversification of skeletal and stereochemical features of fused molecules bearing complex three-dimensional structures.

Overview

By emulating biogenetic route to natural products biosynthesized by plants such as periwinkle, we have developed artificial assembly line generating unprecedented numbers of scaffold variations of indole alkaloids (see illustration).

A multipotent intermediate (inside the orange sphere) was designed with intentions only to stabilize a short-lived biosynthetic intermediate but also to control its cyclization modes, which enabled programmable syntheses of five distinct alkaloidal skeletons (green/purple spheres).

The efficiency of the versatile assembly line was demonstrated by successful total synthesis of three types of naturally occurring indole alkaloid produced by plants.

As this synthetic approach is capable of cost-effective productions of a series of natural products and their structural variants with different skeletal, stereochemical and functional group properties without simplifying the complex structures of alkaloids, it will open new avenues for the development of anti-cancer agents with fewer side effects.

These results were published in the electronic version of the UK scientific journal Nature Chemistry on November 24.

Inquiries

Hiroki Oguri, Associate Professor, Graduate School of Science, Hokkaido University

TEL:+81-11-706-3429

FAX:+81-11-706-3448

E-mail: oguri@sci.hokudai.ac.jp

Division of Chemistry

Japanese Link http://www.hokudai.ac.jp/news/1311125_pr_sci.pdf
Publications Nature Chemistry (2013.11.24)

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