2.2.1. Petromyroxols

In 2015, Li reported the isolation of (+)- and (−)-petromyroxols (**9**) [24]. They are oxylipids isolated from water conditioned with larval sea lamprey *Petromyzon marinus* L. Interestingly, these molecules are the first tetrahydrofuran acetogenindiols isolated from a vertebrate animal (Figure 4). The absolute configuration of each enantiomer was determined by a combination of Mosher ester analysis and comparison with related natural and synthetic products. The **(+)-9** shows a potent olfactory response of 0.01 to 1 μM in the sea lamprey, while the (−)-isomer has a softer effect. Synthetic routes towards them were recently reviewed [18].

**Scheme 1.** Stereodivergent synthesis of *trans-* and *cis*-oxylipids **1** and **2** by Kim.

**Figure 4.** Structures of (+)-and (-)-petromyroxol **9**.

A recent example of the synthesis of **(+)-9**, along with all possible diastereoisomers, was presented in 2020 by Ramana and coworkers [25]. The synthetic route started from the commercial THF compound **10** (Scheme 2). The alkyl chain was installed by reaction with the appropriate cuprate. Subsequent benzyl protection of **11** afforded **12**, which after reaction with allyltrimethylsilane, yielded the desired diastereomer (7:2 ratio) of the allylated THF **13**. After protection with a para-nitrobenzoate (PNB) group under Mitsunobu conditions, compound **14** was subjected to oxidative olefin cleavage with OsO4/NaIO4 and subsequent Wittig olefination to obtain a-b-unsaturated ester **15**. Hydrogenation with Pearlman catalyst (20% Pd(OH)2/C) afforded **16** in 89% yield, where the benzyl group, the double bond, and the nitro group were all reduced. Finally, hydrolysis of both ester groups with KOH in methanol afforded the desired (+)-petromyroxol in 77% yield.

**Scheme 2.** Synthesis of (+)-petromyroxol by Ramana and coworkers.
