**1. Introduction**

Marine organisms are a source of intriguing and fascinating compounds. These living beings have continuously evolved over time, since they are part of the oldest habitat on earth. Being also the largest ecosystem, the ocean has the potential to offer innumerable compounds with interesting biological activities ye<sup>t</sup> to be discovered [1]. This is supported by the fact that hundreds of new molecules are reported within the scientific community every year [2–4].

Usually, the isolation of pure active compounds is a time-consuming and expensive process, due to the need of efficient extraction processes and sequential purification steps. Moreover, large amounts of raw materials have to be collected to finally isolate fairly low quantities of the desired compounds.

Fortunately, the grea<sup>t</sup> contribution of chemists in the field of total synthesis and asymmetric catalysis over the last decades has had countless benefits. On one hand, even though nuclear magnetic resonance (NMR) techniques are very powerful tools, in some cases, the characterization of complex molecules can be difficult, leading to misassignments [5]. Fortunately, total synthesis has emerged as a—somewhat—costly but effective tool for the determination of the absolute configuration of marine metabolites. On the other hand, synthesis provides access to sufficient quantities of the desired compounds for further extensive biological studies.

Within the marine-derived metabolites, terpenes represent one of the most significant families. They are a large and diverse group of compounds that usually present valuable pharmacological properties. Various reviews summarize the discovery of a high number of these metabolites in recent years from different sources, namely sponges [6,7], fungi [8–10], and corals [11,12], among others [13,14].

Other common structural motifs present in marine drugs are heterocycles. Within them, five-, six-, and seven-membered oxygenated heterocycles are frequently found in such bioactive compounds. The six-membered tetrahydropyrans, the most abundant, are

**Citation:** González-Andrés, P.; Fernández-Peña, L.; Díez-Poza, C.; Barbero, A. The Tetrahydrofuran Motif in Marine Lipids and Terpenes. *Mar. Drugs* **2022**, *20*, 642. https:// doi.org/10.3390/md20100642

Academic Editor: Marialuisa Menna

Received: 20 September 2022 Accepted: 12 October 2022 Published: 15 October 2022

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common targets of study [15,16]. The corresponding seven-membered oxepanes, and their appearance in relevant bioactive marine compounds, were reviewed by our group [17]. Regarding tetrahydrofurans, Fernandes and coworkers recently reviewed the most iconic examples of total synthesis of 2,3,5-trisubstituted tetrahydrofuran-containing natural products [18,19]. We have also recently summarized the synthesis and biological properties of marine-derived tetrahydrofuran-containing compounds, focusing on the polyketide family [20].

Continuing our series, here we give an overview of tetrahydrofuran-containing marine drugs, focusing on the terpene family and related compounds. We searched SciFinder for tetrahydrofuran-containing compounds with biological activity, focusing on the period 2000–2022. Our search was refined to compounds of the terpenoid family of compounds of marine origin, finding 81 compounds (Table 1). The main source (see Figure 1) was algae (32 compounds), followed by sponges (19 compounds), fungi (15 compounds), lampreys (6), bacteria (5), and corals (4). Excluding nonterpenoid lipids, we found 55 terpenoid compounds (see Figure 2), most of them being triterpenes (23) followed by meroterpenes (14), monoterpenes (9), diterpenes (5) and, finally, sesquiterpenes (4).

**Figure 1.** Distribution of the number of metabolites from this review, according to their marine source (color code coincides with that of Table 1).
