Structure‐Pattern‐Based Total Synthesis

Abstract

In this article the concept of structure‐pattern‐recognition and its application to total synthesis is summarized. By applying this synthetic strategy to the two biogenetically unrelated natural product families Sarpagine and Stemona alkaloids, a drastic increase of synthetic efficiency could be achieved. To highlight its potential, this strategy is compared with some elegant target‐oriented syntheses. The importance of strategic planning and synthesis design is clearly demonstrated.

Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloids

“…1. Because of their characteristic indole-fused azabicyclo[3.3.1]-nonane structures and prominent biological activities, sarpagine-ajmaline-koumine related alkaloids have attracted attention from the organic synthetic community for decades [17][18][19][20][21][22][23][24][25] . Synthetic efforts have resulted in a number of elegant strategies and culminated with the synthesis of a series of sarpagine˗ajmaline-koumine type alkaloids.…”

“…The last category is Kwon's intramolecular Friedel-Crafts acylation approach 54 . Numerous sarpagine˗ajmaline-koumine type alkaloids have been synthesized based on above-mentioned strategies, however, quebrachidine, vincamedine, and its analogues are not yet conquered to our knowledge by total synthesis [17][18][19][20][21][22][23][24][25] . The natural alkaloid quebrachidine ( 5) and its N-methyl congener vincamajine (6) and vincamedine (7) are among the most highly functionalized and synthetically challenging ajmaline type alkaloids.…”

“…In this work, we report a structure-unit-oriented strategy towards the synthesis of 14 natural monoterpenoid indole alkaloids. Although numerous synthetic methods have been developed for sarpagine-ajmaline alkaloids as well as structurally related analogues, flexible and unified synthetic routes that lead to collective synthesis of these types of alkaloids, especially towards both 19-E and 19-Z isomers, are rarely documented [17][18][19][20][21][22][23][24][25] .…”

Natural Product Synthesis: The Endless Quest for Unreachable Perfection

“…A creative solution to this challenge has been found by using a same strategy to reach various natural products . Sometimes termed “divergent synthesis”, “collective synthesis” as defined by MacMillan, or “structure-pattern-based synthesis” as phrased by Gaich, this approach relies on the identification of a key common intermediate which already bears part of the complexity of a natural product, from which diversity could be accessed in the late stages of the synthesis. These approaches have led to various successes in recent years.…”

Towards the Sarpagine‐Ajmaline‐Macroline Family of Indole Alkaloids: Enantioselective Synthesis of an N‐Demethyl Alstolactone Diastereomer

“…The common structural feature of this family of indole alkaloids is the presence of an eight‐membered ring, either in its native form or embedded in a bridged [3.3.1] bicyclic structure (Scheme , highlighted in red). Total synthesis of this class of natural products has attracted the attention of synthetic chemists for many years . The representative approaches developed by Tamelen, Kutney, Cook, Martin, Kuethe, Kwon, Craig, and Gaich are depicted in Scheme .…”