1. Sesquiterpenes
The reported investigations revealed the purification of various classes of sesquiterpenes that are substituted by isonitrile or isothiocyanate functionalities, including mono-, bi-, and tri-cyclic skeletons with 3-, 5-, 6-, and/or 7-membered rings (
Figure 1 and
Table 1). Frequently, formamide derivatives were reported along with both isothiocyanate and/or isonitrile moieties. Isonitrile-containing metabolites have been reported from some species belonging to
Penicillium and
Axinella genera
[1]. Several reports stated their characterization from
Acanthella. It was reported that
A. cavernosa (Dendy, 1922) can convert cyanide and thiocyanate for isocyanide and isothiocyanate biosynthesis, which could be attributed to the presence of rhodanese or the equivalent enzyme
[2]. Therefore, thiocyanate was postulated to be the precursor for the isothiocyanate moiety in terpenes by direct utilization or oxidative desulphurization of cyanide, conversion to isocyanide terpenes, and reinsertion of sulfur
[2].
Figure 1. Classes of sesquiterpenes reported from the genus Acanthella.
Table 1. Sesquiterpenes from the genus Acanthella (molecular weight and formulae, chemical class, species, and sampling locations).
1.1. Aromadendrane-Type Sesquiterpenes
In 1987, l-isocyanoaromadendrane (
3) was reported as a novel isonitrile sesquiterpene from the fish toxic CH
2Cl
2 fraction of
A. acuta using SiO
2CC (silica gel column chromatography), assigned by spectral and chemical methods
[5].
Furthermore,
5 and
9 were isolated from Japanese
A. cavernosa by SiO
2 CC and RP-HPLC and identified by different spectroscopic methods
[11]. Ximaocavernosin O (
11) was isolated from an
A. cavernosa Et
2O fraction using silica gel/MCI/Sephadex LH-20/(RP)-HPLC/chiral-phase HPLC and was characterized by spectroscopy, X-ray diffraction, and QM-NMR analyses as well as Mosher’s method and TDDFT-ECD calculations
[4]. Compound
11 is similar to
2 and was formerly reported from nudibranch
Hexabranchus sanguineus with a C-10 phenyl urea fragment instead of a C-10 formamide in
2 [4]. New aromadendrane-type sesquiterpenoids,
16 and
12, were purified from the Hainan
A. cavernosa using SiO
2/Sephadex LH-20 CC/chiral-phase HPLC by Shen et al.. Their configurations were elucidated based on spectral, TDDFT-ECD, and X-ray analyses and optical rotation measurements. Compound
16 with a 2S/4S/5R/6S/7S configuration ([α]
D +169.6]) is identical to 2β-hydroxyaromadendr-1(10)-en-9-one ([α]
D _186]) except for the optical rotation (
Figure 2)
[4].
Figure 2. Aromadendrane-type sesquiterpenes (1–16) reported from the genus Acanthella.
1.2. Spiroaxane-Type Sesquiterpenes
Spiroaxane skeletons containing sesquiterpenes are of rare natural occurrence. Compound
19, a new sesquiterpene isocyanide with a spiroaxane (spiro
[25][26] decane) skeleton was obtained from Chinese
Acanthella sp., which is a 3-oxo derivative of
17 [12]. Additionally,
23 is a spiroaxane sesquiterpene with a C-6 isocyanate and was purified and characterized by Jumaryatno et al. from
A. cavernosa specimens collected from Coral gardens/Gneerings reef/Mooloolaba/Australia and from
A. klethra collected from Pelorus Island, Queensland, in addition to
17 [8][16].
Additionally,
23–
30 were isolated from
A. cavernosa Et
2O fractions using silica gel/MCI/Sephadex LH-20/(RP)-HPLC/chiral-phase HPLC and characterized by spectral, X-ray diffraction, and QM-NMR analyses as well as Mosher’s method and TDDFT-ECD calculations
[4]. Compounds
23–
30 are spiroaxane derivatives involving compounds with C-6 isothiocyanate (e.g.,
23–
25) and formamide or a 1-phenethyl urea fragment (e.g.,
26–
30)
[4] (
Figure 3). In 2019, Wu et al. reported the purification of axamide-3 (
32) from the acetone fraction of
A. cavernosa collected from Xidao Island (Hainan Province, China) which was characterized by NMR spectral data and optical rotation
[22].
Figure 3. Spiroaxane-type sesquiterpenes (17–33) reported from the genus Acanthella.
1.3. Eudesmane-Type Sesquiterpenes
Acanthellin-1 (
34) is a bicyclic sesquiterpene with isopropylidene and isonitrile moieties. It was separated as an optically active oil from the ether fraction of the acetone extract of
A. acuta collected from the Bay of Naples using SiO
2CC, and was characterized by NMR and chemical methods, as well as optical rotation
[1] (
Figure 4). A chromatographic investigation of
A. klethra collected from Pelorus Island, Queensland, yielded sesquiterpenoids with isothiocyanate and isonitrile groups, i.e.,
42,
44, and
45, that were assigned by spectral and X-ray analyses. Compounds
42,
44, and
45 are of eudesmane-type and are related to
34. Compounds
45 and
44 are different in stereo-configuration at C-7
[16][17]. Additionally,
39 and
43 are in the bicyclic cis-eudesmane class of sesquiterpenes, possessing isocyanate and isothiocyanate functionalities, respectively, and were purified and specified from
A. acuta [21], whereas
35 is a stereoisomer of
5 [20].
Figure 4. Eudesmane-type sesquiterpenes (34–45) reported from the genus Acanthella.
Axiriabiline A (
38) was obtained from the acetone fraction of
A. cavernosa collected from Xidao Island (Hainan Province, China) and characterized by NMR spectral data and optical rotation
[22]. Burgoyne et al. (1993) purified two new sesquiterpenoid acanthenes B and C (
35 and
37) along with
40 and
42–
44 from the hexane fraction of unidentified
Acantbella species using SiO
2 flash CC/HPLC. The compounds were characterized by spectral analyses
[20].
1.4. Cadinene-Type Sesquiterpenes
In 2000, Clark et al. isolated a new sesquiterpene,
46, that has a 1R/6R/7S/10R configuration and C-10 isothiocyanato functionality and [α]
D +3
[18]. In addition, Nogata et al. purified a new sesquiterpene,
65, and the known
67 from
A. cavernosa EtOH extracts utilizing SiO
2/Sephadex LH-20/ODS HPLC. These compounds were assigned based on spectral data and chemical transformations
[23] (
Figure 5). Compound
65 has a C-10 formamido functionality instead of the C-10-OH in
67 [23].
Figure 5. Cadinene-type sesquiterpenes (46–57) reported from the genus Acanthella.
New cadinane-type sesquiterpenoids, ximaocavernosins A–G (
49–
56), were isolated from
A. cavernosa Et
2O fractions using SiO
2/MCI/Sephadex LH-20/(RP)-HPLC/chiral-phase HPLC and characterized by spectroscopy, X-ray diffraction, and QM-NMR analyses as well as Mosher’s method and TDDFT-ECD calculations
[4]. Compounds
49–
56 have cadinane frameworks with a Δ
5,6 double bond and a C-10 isothiocyanate but differ in stereochemistry and oxidation patterns
[4]. In 2019, Wu et al. reported the purification of 10-formamido-4-cadinene (
65) from the acetone fraction of
A. cavernosa collected from Xidao Island (Hainan Province, China), which was characterized by NMR spectral data and optical rotation
[22]. New cadinane-type sesquiterpenoids,
49 and
68–
73, were purified from Hainan
A. cavernosa using SiO
2/Sephadex LH-20 CC/chiral-phase HPLC (
Figure 6). Their configurations were elucidated based on spectral, TDDFT-ECD, and X-ray analyses and optical rotation measurements. Maninsigin D and ximaocavernosin Q were obtained as racemic forms, which were separated into their enantiomers [(+)-
68/(−)-
69 and (+)-
70/(−)-
71] using chiral-phase HPLC
[14].
Figure 6. Cadinene-type sesquiterpenes (58–73) reported from the genus Acanthella.
1.5. Other Sesquiterpenes
New axane sesquiterpenoids,
74 and
75, in addition to
77, were separated from the antifungal hexane fraction of
A. cavernosa collected from the Hachijo-Jima Islands using flash CC/sephadex LH-20/HPLC. They were elucidated based on spectral data
[27]. Compound
74 is a rare oxygenated tricyclic sesquiterpene cyanide belonging to axane-type sesquiterpenes
[27]. Furthermore,
66,
75, 76, and
85 were isolated by SiO
2 CC and RP-HPLC and identified by alpha-D, spectral data, and chemical methods from Japanese
A. cavernosa [11]. Additionally, the new epimaaliane sesquiterpene
79, along with
78, were specified from the antimicrobial acetone extracts of
A. pulcherrima using spectral and optical rotation measurements. Compound
79 is an enantiomer of
78 with an opposite [α]
D value and differs at the ring junction
[6]. Burgoyne et al. purified epimaaliane-type sesquiterpenes
80 and
81 from the hexane fraction of an unidentified
Acantbella species using SiO
2 flash CC and HPLC. The compounds were characterized by spectral analyses
[20] (
Figure 7).
Figure 7. Other sesquiterpenes (74–87) reported from the genus Acanthella.
Notably, Shen et al. proposed that
12, 16,
49,
68–73, and
84 originate from E,E-farnesyl diphosphate (E,E-FPP), as illustrated in Scheme 1
[14].
Scheme 1. Biosynthesis pathway of
12, 16,
49,
68–73, and
84 [14].
2. Diterpenoids
Diterpenoids are among the common metabolites reported from various
Acanthella species. These compounds are characterized by the existence of nitrogenous functionalities such as isothiocyanato, isocyano, and/or formamido groups. These diterpenes are classified into two major classes, kalihinanes and biflorane derivatives, according to the 8C side chain (
Figure 8 and
Table 2). Kalihinanes have a decalin frame structure with C-7-attached dihydropyran, tetrahydropyran, or tetrahydofuran moiety. Additionally, these rings may carry various substituents such as OH, Cl, isothiocyanato, isocyano, and formamido groups or chlorine. They include kalihinenes, kalihinols, and kalihipyranes. Kalihinols are spilt into two main categories, tetrahydrofuran (
I) and tetrahydropyran (
II) groups, according to the C-7 substitution. Commonly, they have
trans-decalin framework with a C-4 or C-5 tertiary alcohol and an isocyanate moiety at C-10 and/or C-5. The first group has a tetrahydrofuran moiety featuring NCS, NC, or Cl at C-15, or the gem-dimethyl is substituted by an isopropenyl moiety, whereas the tetrahydropyran group possesses Cl atom at C-14. Kalihinenes have a Δ
4-trisubstituted double bond and possess similar structural features to kalihinols, while biflorane diterpenoids are a class of kalihinane diterpenes featuring a linear eight-carbon open chain substituent at C-7. Biosynthetically, these metabolites are proposed to result from the cyclization of the biflorane skeleton (trans or cis form) and geranylgeranyl pyrophosphate
[28]. Their stereochemistry has been determined using spectroscopic, X-ray and/or CD analyses, as well as chemical and computational methods.
Figure 8. Classes of diterpenes reported from genus Acanthella.
Table 2. Diterpenes from the genus Acanthella (molecular weight and formulae, chemical class, species, and sampling locations).
2.1. Kalihinols
Kalihinol A (
88) was the first reported member of this diterpenoid class in 1984
[29] (
Table 2). It is a tricyclic diterpenoid belonging to group
II, containing isocyano, hydroxyl, and chlorine moieties. It was separated from the CCl
4 extract of
Acanthella sp. and characterized by NMR and X-ray analyses
[29] and its configuration was assigned as 1S/4R/5R/6S/7S/10S/11R/14S using the CD exciton chirality method
[45] (
Figure 9).
Figure 9. Kalihinol diterpenes (88–102) reported from the genus Acanthella.
In 1987, Chang et al. purified and characterized isocyano-diterpenoids kalihinols A–H (
88,
94,
96–
98,
100,
108, and
111) and X–Z (
125,
127, and
130) from
Acanthella sp. obtained from Guam and Fiji using spectral and X-ray analyses. They differ in the C-7 attached moiety; the tetrahydropyran with C-14 chlorine (e.g.,
25,
88,
98,
130, and
127); or the tetrahydro-furanyl moiety, with 15-NC (e.g.,
97 and
100), 15-NCS (e.g.,
108), 15-C1 (e.g.,
94), or isopropenyl replacing gem-dimethyl (e.g.,
96)
[30] (
Figure 10).
Figure 10. Kalihinol diterpenes (103–117) reported from the genus Acanthella.
Additionally,
101 was isolated as colorless needles from
A. carvenosa by flash chromatography and HPLC. It resembles
100 with a difference in the substitution at C
4 and C
5 [31]. Additionally, new members of the kalihinols family,
114 and
116, along with
125 and
127, were purified from
A.cavernosa collected from Thailand by SiO
2 CC and HPLC and identified by extensive NMR data. Compound
114 is similar to
125 with a C-5-N-formyl instead of the isothiocyanoate moiety in
125 [15]. Compounds
117 and
118 are two novel C-4 formamido analogs of isokalihinols reported from the South China Sea specimen of
A. cavernosa. They have a
trans-decalin ring at C-7 of the tetrahydrofuran and tetrahydropyran rings, respectively. Compound
117 possesses a C-15 chlorine atom and a C-10 isothiocyanato group, whereas
118 is an example of tetrahydropyran-type isokalihinol. They have 1S/4S/5S/6S/7S/10S/11R/14S and 1S/4S/5S/6S/7S/10S/11R/14R configurations, respectively
[38]. From Okinawan
Acanthella sp., new members of kalihinane-type diterpenes,
110,
115, and
129, were purified from the EtOAc fraction using SiO
2 CC and HPLC. Compound
129 is of tetrahydropyran type and is closely similar to
127, with a trisubstituted olefinic bond in
129 instead of the exo-methylene group in
127, while
110 and
115 have three and two isothiocyano groups, respectively
[35] (
Figure 11).
Figure 11. Kalihinol diterpenes (118–130) reported from the genus Acanthella.
In 1994, Trimurtulu et al. reported new diterpene isonitriles,
103 and
113, from
A. carvenosa collected from The Seychelles. Compound
103 differs from
101 in the
trans-decalin ring system configuration, whereas
113 has an isothiocyanate group instead of one of the C-10 isonitrile groups of
103 [39]. Besides, Xu et al. reported new diterpenoids, kalihinols O–T (
119–
124), together with
88,
98,
109,
115, and
126, from
A. cavernosa in the South China Sea using SiO
2 and Sephadex LH-20 CC
[38]. Their structures and stereo-structures were determined by NMR/CD/X-ray analyses
[38]. Compound
119 is structurally similar to
98, with a C-10 isothiocyanate instead of a C-10 isonitrile in
98, whereas
120 is an isocyanato analog of
88 and
123 is a C-5 formamide analog of
126. Furthermore,
121 and
122 are the C-14 epimers of 120 and 115, respectively, and 124 is the C-15-isothiocyanato analog of
97 [38]. Clark et al. in 2000, purified a new kalihinol-type diterpenoid, 8-OH-isokalihinol F (
102), from
A. cavernosa obtained from Heron Island, Great Barrier Reef, Australia, which was structurally similar to
101 with an additional C-8 OH
[18]. In addition, new formamide analogs,
104 and
106, were purified by Bugni et al. in 2004 from two Philippine
A. cavernosa specimens. They featured formamide moieties at C-10 and C-15, respectively, instead of the isonitrile in
100 [36]. Furthermore, a new kalihinol diterpene,
126, was isolated from Hainan
Acanthella sp. by SiO
2 and Sephadex LH-20 CC and was assigned as a C-10 epimer of
127 [13]. Additionally, new α-acyloxy-amide-substituted diterpenoids, kalihiacyloxyamides A–H (
131–
138), were separated from South China Sea
A. cavernosa EtOAc fractions using SiO
2/Rp-18 CC/RP-HPLC that were elucidated based on spectral, X-ray, and CD analyses (
Figure 12). These metabolites featured isobutyl amide (e.g.,
131 and
132), iso-amyl ester (e.g.,
133,
134,
137, and
138), and phenethyl ester (e.g.,
135 and
136) groups
[42].
Figure 12. Kalihinol diterpenes (131–138) reported from the genus Acanthella.
2.2. Kalihinenes
The first member of this group is kalihinene (
139), which was purified from an
A. klethra EtOH extract using SiO
2 CC/Develosil ODS-5 CC/HPLC and assigned by NMR and X-ray analyses
[27]. Furthermore, compounds
143 and
144 were reported as novel monounsaturated kalihinane class diterpenes derived from
A. Cavernosa toxic CH
2Cl
2 extracts against
Artemia salina and
Lebistes reticulatus using VLC/Flash/Rp-18 CC. These two compounds are diastereoisomers of
139 that feature a trans-decalin skeleton instead of the trans-decalin skeleton of kalihinene. On the other hand,
143 and
144 are epimers at C-10
[32]. Additionally,
145 and
146 are tertrahydropyran/trans-decalin and tetrahydrofuran/cis-decalin analogs bearing formamido groups at C-10 and C-15, respectively (
Figure 13). Kalihinene E (
145) is a C-14 epimer of
148 with 1
S/6
S/7
S/10
S/11
R/14
R configuration
[43]. In 1994, Rodríguez et al. purified new diterpenoids belonging to kalihinene and 6-OH kalihinene groups (
148 and
150–
156), along with
139 from
A. cavernosa collected from a Fijian location. These compounds were characterized based on spectral and X-ray analyses as well as biogenetic evidence
[28]. Additionally,
140–
142 are new metabolites reported from
A. carvenosa collected from The Seychelles
[39]. Compound
140 is a C-1 isomer of
139,
141 has C-15 isothiocyanate instead of C-15 isonitrile in
140, and
142 is an isomer of
140 and
139 [39].
Figure 13. Kalihinene diterpenes (139–156) reported from the genus Acanthella.
2.3. Kalihipyrans and Kalihioxepanes
Kalihipyran (
164) is a tricyclic kalihinene-type diterpene with a C-7 isopropenyl-containing dihydropyran moiety and a C-10 isonitrile
[39]. Compound
167 is an isomer of
165 with cis-decalin
[43], while
166 has a C-15 chlorine atom
[33][34]. In 2022, Wang et al. purified new kalihinane diterpenoids, kalihioxepanes A–G (
157–163), from South China Sea
A. cavernosa by the means of SiO
2/Sephadex LH-20/HPLC. The structures were elucidated by spectral and X-ray analyses, in addition to quantum chemical calculation methods
[44] (
Figure 14).
Figure 14. Kalihioxepanes (157–163) and kalihipyrans (164–167) diterpenes reported from the genus Acanthella.
These metabolites possess a rare C-7-attached oxepane ring with a C-14 Cl atom. Compounds
157–
160 have a
trans decalin skeleton; however,
161–
163 have a cis-decalin skeleton with C-10 isonitrile (e.g.,
157 and
158) and formamide (e.g.,
159–
163) groups
[44]. Wang et al. proposed that
157–
163 are biosynthesized using geranylgeraniol as a precursor (Scheme 2). The latter undergoes a series of reactions, including cyclization, double-bond migration, nucleophilic addition, and oxidation reactions, to give epoxide biflorane (
A, the key intermediate). Nucleophilic substitution of biflorane forms
157 and
158. After that, hydration generates
159–
161 which are then dehydrated to give
162 and
163, respectively
[44].
Scheme 2. Biosynthesis of kalihioxepanes A–G (
157–
163)
[44].
2.4. Biflorane Diterpenes
From the Japanese
A. cavernosa, biflora-4,9,15-triene (
168) was separated, which is a rare biflorane diterpene related to
66, by replacing the methyl hydrogen of the isopropyl group of
66 with a prenyl group
[11]. In 2012, Xu et al. reported
169–172 from CH
2Cl
2 extracts of South China Sea
A. cavernosa, bearing a C-10 formamide group that varied in the decalin moiety (
cis or
trans) configuration and nature of C-7-linked side chain
[43] (
Figure 15). Their structures were assigned by spectral and X-ray analyses. Compounds
169,
170, and
172 are
trans-decalin derivatives, with a C-7 isoprenoid unit, a mono-olefinic isoprenoid sidechain, and a trisubstituted epoxide in the side chain, respectively. In contrast,
171 had a
cis-decalin moiety
[43].
Figure 15. Biflorane (168–174) diterpenes reported from the genus Acanthella.
Investigation of
A. cavernosa DCM/MeOH extracts led to the separation of two oxirane analogs with a trans-decalin framework,
173 and
174, featuring a trisubstituted epoxide and a terminal epoxide group in the side chain, respectively. Compound
174 was suggested to be a precursor of the kalihipyran skeleton
[18]. Clark et al. proposed that the biosynthesis of pyranyl and furanyl kalihinols involves epoxidation of the bifloradiene precursor’s terminal double bond by a nucleophilic attack at either epoxide end by a cyanide ion to form a hydroxyisocyanide. The latter initiates cyclisation to afford a bicyclic system (Scheme 3). Compounds
173 and
174 are alternative epoxidation products. Compound
174 was suggested to be a precursor of the kalihipyran skeleton
[18].
Scheme 3. Biosynthesis of
140,
164, and
174 [18].
3. Alkaloids
Several reports have stated the isolation of different classes of alkaloids from this genus. It is noteworthy that bromopyrrole alkaloids are the dominant type reported from the species of this genus. Oroidin 177 is the first member of pyrrole 2-aminoimidazole alkaloids. These alkaloids were reported to have significant bioactivities, as well as chemical defense against predator fish.
In 2010, Hammami et al. purified a novel bromopyrolimidazole analog,
178, along with
177 from Tunisian
A. acuta diethyl ether extracts
[19]. Four bromo-pyrrole alkaloids, including novel alkaloid hanishin (
179) in addition to
175–
177, were isolated from
A. carteri collected from the northern coast of Hanish Island, Yemen, South Red Sea, by Mancini et al. Compounds
177 and
179 are members of the oroidin family of alkaloids that are considered condensation products of prolines. Compound
179 was proposed to be derived from aminoimidazolinone (
I) or amino acid (
II) intermediates through 1N-C9 cyclization with subsequent side-chain oxidative breakdown
[46] (Scheme 4).
Scheme 4. Proposed biosynthesis of
179 [46].
Mattia et al. purified
180 as a brominated alkaloid from Red Sea
A. Aurantiaca BuOH extracts. The compound features an aminooxodihydroimidazole ring linked to a pyrroloazepine group via a double bond (
Figure 16)
[47]. Compounds
180 and
181 were obtained from
A. aurantiaca BuOH extracts using Sephadex LH-20 and crystallization and were characterized by spectral and X-ray analyses
[48]. In 2014, Macabeo and Guce reported the bromopyrrole-imidazole alkaloids
182–
184 from CH
2Cl
2-MeOH extracts of
A. carteri from The Philippines
[49], while
185 is a pyrrole alkaloid isolated from the n-BuOH fraction of
Acanthella sp. using Sephadex LH-20/Rp-18 CC
[50].
Figure 16. Alkaloids (175–185) reported from genus Acanthella.
A series of synthetic reactions including Suzuki–Miyaura coupling and debromination resulted in natural analogs
186 and
187, in addition to new synthetic derivatives (−)-4-bromo-5-phenylphakellin and (−)-4,5-diphenylphakellin. It was found that the C-5 Br substitution with phenyl or H led to a loss in activity, revealing that the C-5 Br is important for α2B adrenoceptor agonistic activity (Scheme 5)
[51].
Scheme 5. Semisynthesis of (−)-dibromophakellin (
188) derivatives
[51].
Furthermore,
190 was purified from
A. carteri using Sephadex LH-20/SiO
2 CC, giving a bright-orange color with a diazotized benzidine. The compound was characterized by NMR and X-ray analyses, as well as chemical methods. Compound
190 is a 6R/10S brominated alkaloid with a fused C-C pyrrole linkage to the cyclic guanidine core belonging to the
189 series
[52].
In 2002, Wiese and his group reported the synthesis of
190 using dihydrooroidin that is converted to
188 (Scheme 6). Then, thermal rearrangement of
188 in the presence of K
2CO
3 produces
190 [53].
Scheme 6. Synthesis of
190 using dihydrooroidin
[53].
Additionally, Grkovic et al. were able to separate tricyclic-guanidine-containing alkaloids, including a new analog mirabilin K (
192), along with
191 and
193, from
A. cavernosa collected in Southwestern Australia using diol flash chromatography/Rp-18/HPLC. The compounds were characterized by spectroscopic analyses and optical rotation measurements. Compound
192 has a 4
S*/7
S*/9
R*/11
S*/12
R* configuration, which differs from
191 in the C9-CH
3 group and with the presence of a N-substituted methine group (
Figure 17)
[54]. Furthermore,
194 and
195 were obtained by Fan et al. from the acetone extracts of
A. cavernosa collected from the South China Sea
[24].
Figure 17. Alkaloids (186–195) reported from the genus Acanthella.
Diketopiperazines, including the rare cyclo(L-Phe-L-Thr) and cyclo(L-Tyr-L-Ile) (
196–
202), along with decarboxylated amino acid
207 and deoxyribonucleotides
203–
206, were reported and characterized from Fijian
A. cavernosa (
Figure 18). Their L-L absolute configuration was assigned based on an NMR and CD comparison with synthetic L-L analogs, as well as optical rotation measurements
[55].
Figure 18. Alkaloids (196–207) reported from the genus Acanthella.
4. Steroid Compounds
In 2008, Qui et al. reported the purification of three new nor-steroids,
208–
210, along with the known steroids
211–
214 from the petroleum ether fraction of
A. cavernosa obtained from Hainan Island, China, using SiO
2 CC/HPLC. The new steroids are related to A-ring-contracted steroid analogs featuring carbonyl and ketone groups located at C-3 and C-4; they differ in their C-17 side chains
[56] (
Figure 19). In addition,
215 was obtained from the acetone extract of the same sponge collected from the South China Sea
[24].
Figure 19. Steroid compounds (208–215) reported from the genus Acanthella.
5. Other Metabolites
Compound
216 was separated from
A. vulgata acetone extracts using an MgO column and crystallization from petroleum ether. The compound belongs to carotenoids, as it has a polyene chain with terminal aromatic moieties on both ends
[57] (
Figure 20). Mancini et al. were able to purify and characterize
219, a novel methyl-branched glycerol enol ether, and the related linear analog
218 from
A. carteri obtained from Southern Red Sea Hanish Islands by utilizing flash CC/HPLC and spectral and chemical methods
[58]. Compound
219 has an additional methyl group at C-2 of the sidechain compared to
218, and both have a 2`S configuration
[58]. In 2010, Hammami et al. separated the sesterterpene
217 and cerebrosides
220–
222 from Tunisian
A. acuta diethyl ether extracts
[19], whereas
226 was purified from the Chinese
A. cavernosa by Fan et al.
[24].
Figure 20. Other metabolites (216–226) reported from the genus Acanthella.
This entry is adapted from the peer-reviewed paper 10.3390/md21040257