**1. Introduction**

The ocean is the biggest ecosystem of our planet. Plenty of organisms live in the ocean, and new species are discovered every year. As well, being the oldest ecosystem, marine organisms have evolved for a longer time than terrestrial living beings, and thus have different and sometimes better mechanisms of defense. These are represented by specific compounds, like toxins found in fish and algae and other bioactive substances found in sponges or tunicates. Usually, the real producers of these compounds are microorganisms such as bacteria, cyanobacteria, or dinoflagellates. The interesting properties of some of these metabolites have attracted the attention of the scientific community. As they are usually scarce and difficult to obtain in large amounts, total synthesis has emerged in the last decades as a necessary tool to tackle this problem. It has helped to clarify the structure of some intriguing compounds, and to obtain higher amounts of them in order to perform proper biological studies. Total synthesis is still a crucial tool, as even with today's advanced NMR techniques, misassignment of the structure of biologically relevant macrolides is a common issue [1].

Polyketides are a diverse class of metabolites, comprising linear as well as macrolide compounds with a range of biological activities. Some of them have promising potential as drug candidates [2]. Common sources of this class of compounds are dinoflagellates of the genus *Amphidinium* [3]. To understand how to access the macrolide core present in these and other structures within natural products, we encourage the reader to review general macrolactonization methods [4].

On the other hand, oxygenated heterocycles are common motifs in marine bioactive compounds, and therefore the development of methods for their synthesis also requires attention. The most common are six-membered oxacycles, tetrahydropyrans, and thus numerous works focus on their synthesis [5,6]. Oxepanes and tetrahydrofurans also appear in a very large number of marine natural products with interesting properties. 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].

Continuing our interest for marine heterocyclic compounds, here we provide an overview, from 2013 to October 2021, of tetrahydrofuran-containing marine polyketides.

**Citation:** Fernández-Peña, L.; Díez-Poza, C.; González-Andrés, P.;Barbero, A. The Tetrahydrofuran Motif in Polyketide Marine Drugs. *Mar. Drugs* **2022**, *20*, 120. https://doi.org/10.3390/ md20020120

Academic Editor: Vassilios Roussis

Received: 2 January 2022 Accepted: 1 February 2022 Published: 3 February 2022

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The compilation of literature on THF-containing macrolides up to 2012 was covered in an excellent review [10]. Macrolides is such a fertile field that some particular families of compounds have already been reviewed, such as haterumalides and biselides [11], or more recently, mandelalides [12]. In recent years, numerous synthetic approaches to the polyketide family continue to emerge, and here we offer an overview of them.

#### **2. Polyketide Marine Drugs Containing Tetrahydrofuran Rings**
