Contiguous Quaternary Carbons: A Selection of Total Syntheses.

Alina Eggert,Dennis Lübken,Christoph Etling,Marius Saxarra,Markus Kalesse

doi:10.3390/molecules25173841

Abstract

Contiguous quaternary carbons in terpene natural products remain a major challenge in total synthesis. Synthetic strategies to overcome this challenge will be a pivotal prerequisite to the medicinal application of natural products and their analogs or derivatives. In this review, we cover syntheses of natural products that exhibit a dense assembly of quaternary carbons and whose syntheses were uncompleted until recently. While discussing their syntheses, we not only cover the most recent total syntheses but also provide an update on the status quo of modern syntheses of complex natural products. Herein, we review (±)-canataxpropellane, (+)-waihoensene, (–)-illisimonin A and (±)-11-O-debenzoyltashironin as prominent examples of natural products bearing contiguous quaternary carbons.

Highlights

In 2016, the groups of Overman and Hanessian published a well-arranged review about synthetic strategies for natural products bearing contiguous stereogenic quaternary carbons [1]
By focusing on already completed challenges in natural product synthesis, they adverted to still unsolved synthetic problems [1]
The Gaich group succeeded in the first total synthesis of a complex taxane diterpene, canataxpropellane (1)

Summary

Introduction

In 2016, the groups of Overman and Hanessian published a well-arranged review about synthetic strategies for natural products bearing contiguous stereogenic quaternary carbons [1]. By focusing on already completed challenges in natural product synthesis, they adverted to still unsolved synthetic problems [1]. Taxane-derived propellane skeletons and terpenes, as well as terpenoids bearing contiguous asymmetric quaternary carbons, are mentioned to be one of the most exciting future challenges. In 2020, Gaich and coworkers published the first total synthesis of canataxpropellane (4) [2,3], a previously highlighted future challenge. Waihoensene (23) was successfully synthesized by Lee and coworkers in 2017 [4]. Syntheses of waihoensene (23) by the groups of Yang and Snyder followed [5,6]. This review covers a recent synthesis of (±)-11-O-debenzoyltashironin (55) by Wang and coworkers [7] and the first synthesis of illisimonin A (72) published by Rychnovsky and Burns [8]

Gaich’s Synthesis of Canataxpropellane

C-20 C–C-bond was achieved byopening the reductive lactoneoxidation opening of

Retro aldol fragmentation–aldol–photooxygenation sequence towards synthesis

Inversion at C-5 carbonylation of C-8 towards synthesis of canataxpropellane

20. Acetylation of the alcohols at

Waihoensene

Synthesis

Endgame

Wang’s

67. Oxidation using

Construction

16. Rychnovsky