3.2.1. Sesquiterpenoids

Sesquiterpenoids are the largest group of known terpenoids [72]. The mangrove fungiderived sesquiterpenoids possess a variety of carbon skeletons, including monocyclic, bicyclic, and tricyclic types [73].

One tricyclic and three spirobicyclic norsesquiterpenoids (**64**–**67**) (Figure 17) were isolated from the endophytic fungus *Pseudolagarobasidium acaciicola* (from the mangrove *Bruguiera gymnorrhiza*) [74,75]. Among them, acaciicolin A (**64**) possesses a previously unknown skeleton with a uniquely connected 6/5/5 ring system and three consecutive oxygenated sp<sup>3</sup> quaternary carbons at C-7, C-8, and C-8a. The norsesquiterpene skeleton of **64** was named "acaciicolane", and was different from the three known sesquiterpene skeletons with 6/5/5 ring systems: cedrane, prezizaane, and zizaane (Figure 18). Spiroacaciicolides A–C (**65**–**67**) has a hitherto unobserved 5/6 fused spirobicyclic ring system. The absolute configurations of the new compounds **64**–**66** were determined by single-crystal

X-ray analysis (Cu-K*α* radiation). **64**–**67** could originate from chamigrane endoperoxide A [76] (Scheme 9).

**Figure 17.** Structures of compounds **64**–**69**.

**Figure 18.** Structures of five sesquiterpene skeletons.

**Scheme 9.** Proposed biosynthetic pathway for compounds **63**–**66** [74].

Penicibilaenes A (**68**) and B (**69**) (Figure 17), two sesquiterpenes possessing a tricyclo[6.3.1.01,5]dodecane skeleton constituted by [3.3.1]-bridged and [4.3.0]-fused junctions, were characterized from *Penicillium bilaiae* MA-267, a fungus obtained from the rhizospheric soil of the mangrove plant *Lumnitzera racemosa* [77]. An X-ray crystallographic study determined the structure and configuration. The hypothetical biosynthetic pathway starting from *cis*-farnesyl pyrophosphate (FPP) was proposed (Scheme 10). Notably, Compounds **68** and **69** exhibited selective activity against the plant pathogenic fungus *Colletotrichum gloeosporioides* (MIC = 1.0 and 0.125 *μ*g/mL, respectively).

**Scheme 10.** Proposed biosynthetic pathway for compounds **68** and **69** [77].

The first total synthesis of **68** and **69** in their racemic forms was reported by Dong et al. in 2021 [78]. The approach featured a rhodium-catalyzed deconstructive formation of a tricyclic skeleton by C–C activation of cyclobutanone derivatives, generating ( ±)-**68** and (±)-**69** in 13 and 14 steps with 0.56% and 0.49% overall yields, respectively. In the same year, K Sugita described another more efficient synthetic pathway for the total practical

synthesis of (±)-**68** and (±)-**69** from commercially available 3-ethoxycyclohex-2-en-1-one with 4.0% overall yields for both compounds [79].
