Advances in Total Synthesis of Some 2,3,5‐Trisubstituted Tetrahydrofuran Natural Products

Abstract

2,3,5‐Trisubstituted tetrahydrofuran moiety is ubiquitous in natural products. These have served as appealing candidates for total synthesis due to their varied bio‐ and pharmaceutical activities. This tutorial review delineates the ingenious efforts by many researchers in the total synthesis of selected natural products based on a common 2,3,5‐trisubstituted tetrahydrofuran core structure. Many of the syntheses display nuanced interplay between new methods and the ingenuity of planned strategies achieved through catalysis or cascade chemistry. In some cases, the chiron approach has come quite handy, wherein the structural features and the stereochemistry in select molecules could map well with naturally available starting materials. This compilation also aims to enhance the diversity space based on these natural products and further interest in sustainable total synthesis.

The Tetrahydrofuran Motif in Polyketide Marine Drugs

“…Oxepanecontaining marine compounds were recently reviewed by our group [7]. Total syntheses of marine and non-marine products containing 2,3,5-trisubstituted tetrahydrofurans (such as kumausallene or petromyroxol) have been recently reviewed by Fernandes [8,9].…”

Synthetic Approaches to Diospongins: A Two Decade Journey

“…Oxygen-containing heterocyclic compounds, especially tetrahydrofurans and tetrahydropyrans, are important scaffolds in many biologically active compounds. 1 2 3 4 Diospongins belong to a family of cyclic 1,7-diarylheptanoids isolated from rhizomes of Dioscorea spongiosa in 2004 by Kadota et al Diospongins have 2,6- cis - and 2,6- trans -tetrahydro-2 H -pyran rings, as a core, constructed by intramolecular cyclization of 5,7-dihydroxy-1,7-diphenyl-2-hepten-1-one, in their biosynthesis. Moreover, these compounds possess a trisubstituted tetrahydropyran unit with different stereochemistries at C-3.…”

The Tetrahydrofuran Motif in Marine Lipids and Terpenes

“…The corresponding seven-membered oxepanes, and their appearance in relevant bioactive marine compounds, were reviewed by our group [7]. Regarding tetrahydrofurans, Fernandes and coworkers lately reviewed the most iconic examples of total synthesis of 2,3,5-trisubstituted tetrahydrofuran-containing natural products [8], [9]. We have also recently summarized the synthesis and biological properties of marine-derived tetrahydrofuran-containing compounds, focusing on the polyketide family [10].…”