# Trepenoids in Marine Heterobranch Molluscs
## 4 Diterpenoids
### Tricyclic Diterpenoids
Finally, this study reports that _Ardeadoris egretta_ also contains regular diterpenes with a spongian framework, with five compounds in the viscera and six in the mantle, while _Doriprismatica atromarginata_ presents also spongian furanoditerpenes, three distributed in viscera and four in the mantle. A recent chemical study of the South China Sea nudibran's _Phyllidiaella pustulosa_ and _Phyllidia coelestis_, as well as their possible sponge prey _Acanthella cavernosa_, led to the isolation of several terpenoids, including a kalihianne-type diterpenoid, bisformamidokalihinol A, along with other three difterpenoids [130]. A series of amphilectene diterpenes, most likely of dietary origin, with isocyano  
Figure 8: Structures of selected diterpenoids from Heterobranch molluscs: (**58**) anisodorin-1; (**59**) Kurosppongin; (**60**) tyrinnal; (**61**) aplysulphurin; (**62**) aplysuolactone; (**63**) aplysroseol-2; (**64**) chromoculatinine C; (**65**) gracillin A; (**66**) daphnolactone; (**67**) verrielactone; (**68**) verrucosin-1; (**69**) verrucosin A; (**70**) tritoniopsin C.  
and formamido functionalities has been recently reported in _Phhylidia coelestis_ from South China [215]. The dorid _Hexabranchus sanguineus_ from South China also presents a diterpene in its internal tissues, as well as other compounds probably from its diet sponge [142]. Some natural products of heterobranchs, particularly in sea slugs and sea hares, include different combinations of terpenoids with glycerides, guanidines, and others. These include the diterpene glycerides found in several doridacean slugs, such as the Mediterranean _Doris verrucosa_, possessing the verrucosa 1-9 (68) (Figure 8) [15,216] and a further series of diterpenoid glycerides. Among these compounds, verrucosin A (69) (Figure 8) is de novo biosynthesized, as demonstrated in experiments with \({}^{13}\)C- and \({}^{14}\)C-labelled precursors [217; 218; 219]. Biosynthesis is commonly found in this group [3]. Another example is the doridacean _Archidoris pseudoargus_, which possesses several ichtyotoxic diterpene glycerides in mantle and egg masses in UK specimens [220]. Similarly, _Doris (Austrodis) kerguelenensis_ from several Antarctic locations, presents a series of diterpene diacylglycerol needles in the mantle, which effectively protect them from predation by sympatric sea stars and anemones, along with the corresponding monoacylglycerollycerides, and monoacylglycerolcycles of regular fatty acids [15; 106; 221; 222]. Additional diterpene glycerides and clerodane diterpenes, such as palmadoring, were described in specimens of _D. kerguelenensis_ from diverse Antarctic populations [223; 224]. The existence of different chemotypes in _D. kerguelenensis_ indicates that different terpene synthases may be regulating the biosynthesis of this wide arsenal of terpene glycerides [225], and this may be related to their genetic variability and/or cryptic speciation [225; 226; 227]. Palmadorin A, B, D, M, N, and O inhibit human erythroleukemia cells (HEL) at low micromolar IC\({}_{50}\), while palmadorin M inhibits Jak2, STAT5, and Erk1/2 activation in HEL cells and produces apoptosis at 5 mM [224]. The aeolids _Phhylodesinium briarieuum, P. longicirrum_ and _P. magnum_ possess several diterpenes along with some sesquiterpenes, possibly obtained from their octocoral prey [182; 228]. Further studies report four polycyclic chatancin diterpenes in Australian specimens of _P. longicirrum_, along with other deterrent compounds against fish [229; 230]. Tritoniopsins A-D (70) (Figure 8) are found in the dendronotid _Tritoniopsis elegans_ in China, from its coral prey _Cladiella krempfi_[86; 231]. The arminid _Dermatobranchus ornatus_ from China possesses a calcophiririn diterpenoid in the mantle, suggested to be obtained from its potential gorgonian prey _Muricella_ sp. in South China [232]. _D.