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Article

New Isomalabaricane-Derived Metabolites from a Stelletta sp. Marine Sponge

by
Sophia A. Kolesnikova
1,*,
Ekaterina G. Lyakhova
1,
Anastasia B. Kozhushnaya
2,
Anatoly I. Kalinovsky
1,
Dmitrii V. Berdyshev
1,
Roman S. Popov
1 and
Valentin A. Stonik
1,2
1
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Pr. 100-let Vladivostoku 159, 690022 Vladivostok, Russia
2
School of Natural Sciences, Far Eastern Federal University, Sukhanova Str. 8, 690000 Vladivostok, Russia
*
Author to whom correspondence should be addressed.
Molecules 2021, 26(3), 678; https://doi.org/10.3390/molecules26030678
Submission received: 29 December 2020 / Revised: 23 January 2021 / Accepted: 25 January 2021 / Published: 28 January 2021
(This article belongs to the Special Issue Dedicated to the 55th Anniversary of G.B. Elyakov Pacific Institute of Bioorganic Chemistry of the Far Eastern Branch of the Russian Academy of Sciences)
Browse Figures
Versions Notes

Abstract

:
In continuation of our studies on a Vietnamese collection of a Stelletta sp., sponge we have isolated two new isomalabaricane triterpenoids, stellettins Q and R (1 and 2), and four new isomalabaricane-derived nor-terpenoids, stellettins S-V 3–6, along with previously known globostelletin N. Among them, compound 3 contains an acetylenic fragment, unprecedented in the isomalabaricane family and extremely rare in other marine sponge terpenoids. The structures and absolute configurations of all new compounds were established by extensive NMR, MS, and ECD analyses together with quantum-chemical modeling. Additionally, according to obtained new data we report the correction in stereochemistry of two asymmetric centers in the structures of two known isomalabaricanes, 15R,23S for globostelletin M and 15S,23R for globostelletin N.

1. Introduction

Malabaricanes are rather a small group of tricarbocyclic triterpenoids found in different tropical flowering terrestrial plants [1,2,3]. Isomalabaricanes, which differ from malabaricanes in the configuration of C-8 asymmetric center and have an α-oriented CH3-30, are known as metabolites of four genera of marine sponges—Stelletta, Jaspis, Geodia and Rhabdastrella—belonging to the class Demospongiae. Some of them are highly cytotoxic against tumor cells [4]. Since the first isolation of three yellow highly conjugated isomalabaricane-type triterpenoids from the marine sponge Jaspis stellifera in 1981 [5] more than 130 isomalabaricanes and related natural products have been reported from the abovementioned sponge genera. It was noticed that Stelletta metabolites are quite different depending on the collection. Indeed, isomalabaricane triterpenoids were mainly found as very complex mixtures in tropical sponge samples, while boreal and cold-water sponges contain mostly alkaloids and lipids. From a chemo-ecological point of view, this indicates that studied sponges are able to produce different types of secondary metabolites in order to adapt to the various living conditions [6]. In confirmation, our attempt to find isomalabaricanes in a cold-water Stelletta spp., collected in 2019 in the Sea of Okhotsk, was unsuccessful, as the characteristic yellow pigments were not detected by thin layer chromatography in the extracts of these sponges.
Additionally, in result of the chemical investigation of the sponge Stelletta tenuis, Li et al. identified two naturally occurring α-pyrones, namely gibepyrones C and F, along with three isomalabaricane-type triterpenoids [7]. These α-pyrones were supposed to be the oxidation products of the co-occurring stellettins [6]. Gibepyrone F had previously been isolated from the fungal plant pathogen Gibberella fujikuroi [8], as well as from the sponge Jaspis stellifera [9]. These findings allow to presume that symbiotic microorganisms in the corresponding sponges are involved in the generation of some metabolites.
Diverse isomalabaricane-type nor-terpenoids, containing less than 30 carbon atoms in their skeleton systems, have been found together with isomalabaricanes several times [10,11,12]. Their presence could be explained either by oxidative degradation of C30 metabolites or by precursor role of nor-terpenoids in the biosynthesis of these compounds [12,13]. However, the biogenesis of isomalabaricane compounds in sponges remains to be mysterious so far.
Recently, we have reported the isolation of two isomalabaricane-type nor-terpenoids, cyclobutastellettolides A and B, and series of known isomalabaricanes from a Stelletta sp. [14] We suppose that new data on structural variety of isomalabaricane derivatives supported with strong evidence on stereochemistry could someday shed light on their origin.
In the present work, an investigation of the chemical components of a Stelletta sp. from Vietnamese waters was continued. Herein, we report the isolation and structural elucidation of six new compounds 1–6 and known globostelletin N [15].

2. Results and Discussion

The frozen sample of a marine sponge Stelletta sp. was finely chopped and extracted with EtOH, then the extract was concentrated under reduced pressure and subjected to Sephadex LH-20 and silica gel column chromatography followed by normal- and reversed-phase HPLC procedures (Figure S73) to afford new stellettins Q-V 1–6 together with known globostelletin N [15] (Figure 1).
Stellettin Q (1) was isolated as a yellow oil with molecular formula C32H44O6 deduced by HRESIMS (Figure S3). The NMR data of 1 (Table 1; Figures S4 and S5) were closely related to the spectral characteristics of isomalabaricane globostelletin K (Figure 1, Figures S55 and S56) initially found in the marine sponge Rabdastrella globostellata [15] and also co-isolated from the studied Stelletta sp. [14].
The detailed analysis of 2D spectra (COSY, HSQC, HMBC etc.) of 1 supported the main structure (Figure 2 and Figures S6–S9). The signals of methyl group at δH 2.06, s; δC 21.2 and acetate carbonyl at δC 171.0, together with the HMBC correlation of axial proton H-3 at δH 4.54, dd (11.7, 5.2) to that carbonyl, revealed the O-acetyl substitution at C-3 in the ring A. Moreover, the signal of C-3 at δC 80.8 instead of ketone signal at δC 219.2 in 13C NMR spectrum of globostelletin K also demonstrated the 3-acetoxy-tricyclic core in 1, while the 3β-orientation of acetoxy group was confirmed by strong correlations of H-3/H-5 and CH3-28 observed in the ROESY spectrum. The 13Z geometry in 1 was in agreement with the signal of CH3-18 at δH 1.79, s and its ROESY correlation with CH3-30. As well as E configuration of 24(25)-double bond was found from the W-path COSY correlation of protons H-24/CH3-27.
The 1H- and 13C-NMR signals of the side chain of 1 as well as the form of ECD curve (Figure S10) were analogous to those of globostelletin K [15] (Figure S57) suggesting the same stereochemistry of the side chain. This assignment was in a good agreement with the computational ECD results performed using density functional theory (DFT) with the nonlocal exchange-correlation functional B3LYP [16], the polarization continuum model (PCM) [17] and split-valence basis sets 6-31G(d), implemented in the Gaussian 16 package of programs [18] (Figure S66). The 15R,23S absolute configuration, providing 13Z,24E geometry and trans−syn−trans-fused tricyclic moiety with 3β-oriented acetoxy group fully satisfies the similarity of the experimental and theoretical ECD spectra of 1 (Figure 3). In detailes, statistically avereged curve (Figure 3) follows the shape of the experimental one, although even more close coincidence was indicated for theoretically less probable conformer (Figure S67). In addition, we could conclude that the presence of 3-acetoxy or 3-oxo functions in the structures of the corresponding compounds insignificantly affects the shape of their ECD curves. According to obtained new data we pose the same 15R,23S stereochemistry for globostelletin K (Figure S69).
Stellettin R (2) has a molecular formula of C32H44O6 as it was established on the basis of HRESIMS (Figure S11). Spectral data (Table 1, Figure 2, Figures S12 and S13) were consistent with known globostelletin M [15] (Figure 1, Figures S59 and S60) possessing an isomalabaricane core connected with 13E double bond (CH3-18: δH 2.06, s). However, like stellettin Q, it contains 3β–acetoxy group (δH 4.53, dd (11.6, 5.2); δC 80.7; δH 2.05, s; δC 170.9; 21.2). Concerning to the relative configuration of the cyclopentene unit in the side chain of 2, the ROESY cross-peaks between H-15/H-24 and H-23/CH3-18 ascertained a trans-relationship of the vicinal protons H-15 and H-23. Careful examination of the chemical shifts for CH-15 (δH 3.22, dt (9.2, 6.0); δC 48.0) and CH-23 (δH 3.95, m; δC 48.0) showed the values similar to those of globostelletin M and differed from globostelletin N (Figure 1, Figures S63 and S64) isolated by Li et al. [15] and co-isolated by us. Moreover, the ECD spectrum of 2 (Figure S18) displayed the same curve and peaks as those published for globostelletin M (Figure S61).
However, structure modeling as well as calculation of ECD spectra for possible stereoisomers of 2 demonstrated a good agreement between experimental and theoretical spectra for 15R,23S absolute configuration (Figure 4) quite differ from 15S,23S reported for globostelletin M [15]. This inconsistence encouraged us to re-investigate the stereochemistry of co-isolated globostelletins M and N. We have obtained NMR and ECD spectra of the both compounds (Figures S59–S65) and they were identical to those provided as supplementary data by Li et al. [15]. At the same time, our computational results suggested globostelletin M to possess the same 15R,23S absolute configuration (Figure S70) of cyclopentene unit as 2, while globostelletin N has 15S,23R stereochemistry (Figure S71). Based on the data we believe that previously published research comprises some inaccuracies and the stereochemistry of these centres in corresponding isomalabaricanes should be revised. It was noted that the isomalabaricane-type terpenoids undergo a photoisomerization of the side chain 13-double bond during the isolation and storage [19,20]. We consider compounds 1 and 2 to be the 13Z/E pair of the same 15R,23S isomer.
The molecular formula C19H28O3 of stellettin S (3) calculated from HRESIMS data (Figure S19) showed 3 to be a rather smaller molecule then classical C30-isomalabaricanes, intriguing due to the lack of a significant part in the molecule, when compared with the majority of known isomalabaricanes and their derivatives. The 13C- and DEPT NMR spectra (Table 2; Figures S21 and S22) exhibited 19 resonances, including those of carbonyl carbon at δC 216.5 (C-3) and carboxyl carbon at δC 178.8 (C-12) as well as two down-shifted quaternary carbons at δC 88.1 (C-13), 77.8 (C-14). 1H- and 13C-NMR spectra (Figures S20 and S21) revealed five methyls, two methylene, two methine groups and seven quaternary carbons, suggesting an isoprenoid nature. In the HSQC spectrum (Figure S23) four methyl singlets (δH 1.06, 1.08, 1.25, and 1.62) correlated with carbon signals at δC 21.6 (CH3-29), 25.9 (CH3-28), 30.8 (CH3-30) and 23.3 (CH3-19), respectively, while singlet of one more methyl group at δH 1.80 gave a cross-peak with high field signal at δC 3.7 (CH3-18). The further inspection of 2D spectra (Figure 5 and Figures S23–S26) revealed the bicyclic framework resembling the core of globostelletin A (Figure 5), isolated from the sponge Rhabdastrella globostellata [13].
This was confirmed by the key long-range HMBC correlations from gem-dimethyl group (CH3-28 and 29) to C-3, C-4 and C-5; from H-5 to C-1, C-4, C-6, C-9 and C-10; from methyl CH3-19 to C-1, C-9 and C-10; from methyl CH3-30 to C-7, C-8 and C-9 as well as from the methylene of carboxymethyl group (CH2-11) to C-8, C-9, C-10 and carboxyl carbon C-12 (Figure 5 and Figure S24). The empirical formula, besides bicyclic system and two carbonyls, required two additional degrees of unsaturation which were accounted for an acetylenic bond in a short side chain. The NMR signals of two quaternary carbons at δC 88.1 (C-13), 77.8 (C-14) and methyl (CH3-18) at δH 1.80, δC 3.7 were finally attributed to the methylacetylenic substituent at C-8, that was confirmed by HMBC correlations from CH3-30 to C-8 and C-13, along with that from CH3-18 to C-7, C-8, C-9, C-13, C-14 and CH3-30. Analogous methylacetylenic substituent was characterized previously with similar chemical shifts in a series of synthetic alkynes [21].
Interestingly, the NMR signal of CH3-19 (δH 1.62, s) was notably downfield shifted in comparison with that in a number of isomalabaricanes and their derivatives spectra. We explained it by the joint influence of the methylacetylene and carboxymethyl groups. The quantum chemical calculations (Figure S66) of the chemical shifts for structure 3 confirmed the down-shifted position of the proton signal of CH3-19 and afforded its theoretical chemical shift value of δH 1.69 ppm.
The relative stereochemistry of 3 was determined by ROESY experiment (Figure 6 and Figure S26). A trans-fusion of the bicyclic system was shown by key NOE interactions. The correlations between CH3-19/CH3-29, CH3-28/H-5, H-5/Ha-11, CH3-19/H-9, and CH3-30/Hb-11 showed the β-orientations of CH3-19 and H-9, whereas H-5, CH2-11, and CH3-30 were α-oriented. The chair conformation of the ring B with equatorial positions of H-9 and CH3-30 corresponded to the long-range COSY correlation between H-9 and Hβ-7 (Figure 5 and Figure S25) together with ROESY correlations H-5/Ha-11 and Hα-7/Hb-11. Taking into consideration the relative stereochemistry of the compound 3 along with above mentioned absolute stereochemistry of the C30 congeners 1 and 2 as well as the fact of co-isolation of cyclobutastellettolides A and B [14] with the same absolute configurations we suggested the 5S, 8R, 9R, 10R absolute stereochemistry of stellettin S (3).
Stellettin T (4) with the molecular formula C20H32O5 seemed to be another isomalabaricane-type derivative. The ispection of NMR data (Table 2; Figure 5 and Figures S29–S33) revealed the same type of 9-carboxymethyl substituted bicyclic core as was deduced for compound 3. It contains 3β-acetoxy group, confirmed with the signals of CH-3 (δH 4.44, dd (11.2, 5.1); δC 80.3), methyl of acetate group (δH 2.05, s; δC 21.2) and acetate carbon (δC 170.9). According to the 13C NMR spectrum and molecular formula, compound 4 has one carbonyl less side chain then known globostelletin A [13]. Based on this data and HMBC correlations from CH3-14 (δH 2.12, s) and CH3-30 (δH 1.31, s) to C-13 (δC 213.0), the acetyl was connected with C-8 (δC 52.5). The key ROESY correlations H-3/H-5, H-5/Ha-11, H-14/CH3-19, H-9/CH3-19 and H-9/CH3-29 (Figure S34) suggested configurations at C-5, C-8, C-9 and C-10 identical to those of co-isolated isomalabaricanes.
The structures of stellettins U (5) and V (6) corresponded to the same C19H30O5 molecular formula deduced from HRESIMS (Figures S36 and S45). In comparison with co-isolated metabolites, the spectral data of compounds 5 and 6 revealed bicyclic core with keto group at C-3, gem-dimethyl group at C-4 and two angular methyls at C-8 and C-10 (Table 2). Additionally, 1H- and 13C-NMR spectra of compound 5 (Figures S37 and S38) demonstrated signals of two carbonyls (δC 173.7 and 183.8) and one ethoxy group (δH 4.15, q (7.1); δC 60.8 and δH 1.26, t (7.1); δC 14.1). HMBC experiment (Figure 7 and Figure S41) allowed to place the carboxy group at C-8 and ethyl ester at C-11 on the basis of congruous correlations from methylenes –CH2-CH3 (δH 4.15, q (7.1), 2H) and CH2-11 (δH 2.41, dd (17.7, 5.3) and 2.30, m) to carboxyl C-12 (δC. 173.7) and also from methyl CH3-30 (δH 1.17, s) to carboxyl C-13 (δC 183.8). The relative stereochemistry of 5 was determined by ROESY spectral analysis (Figure S43). Correlation between H-9 (δH 2.78, br t (5.0)) and CH3-19 (δH 1.24, s) indicated their β-orientation. Meanwhile, a ROESY correlation between H-5 (δH 1.40, dd (12.6, 3.0))/Ha-11 (δH 2.41, dd (17.7, 5.3)) and Hb-11 (δH 2.30, m)/CH3-30 (δH 1.17, s) confirmed the α-orientation of H-5, -CH2-COOEt and CH3-30. The above-mentioned results were in agreement with the spatial structure of isomalabaricane derivatives.
Compound 6 was an isomer of compound 5, differed by the NMR signals (Figures S46 and S47) of carboxylic carbons (δC 177.6 and 178.0), methyl C-19 (δH 1.14, s), methylene CH2-11 (δH 2.48, dd (18.1, 5.4) and 2.38, dd (18.1, 4.8)) and ethoxy group (δH 4.23, dq (10.9, 7.1); 4.13, dq (10.9, 7.1) and 1.31, t (7.1)). The key HMBC correlations (Figure 7) satisfied the proposed structure of 6. However, since the values of carboxyl carbons shifts for 6 are close, distinguishing their correlations and direct ester positioning without data for isomer 5 brought some uncertainty. To avoid future difficulties with structurally related esters we calculated carbon chemical shift values for two isomers 5 and 6 (Figure S66). It was shown, that theoretical δC C-13 (5) = 192.7 and δC C-12 (5) = 182.4 gave the ΔδC(13-12) = 10.3 ppm close to experimental value ΔδC(13-12) = 10.1 ppm, while theoretical and experimental ΔδC(13-12) for compound 6 were of 0.4 ppm (clcd δC C-13 (6) = 183.2, δC C-12 (6) = 182.8).
ROESY correlations of 6 supported the relative stereochemistry similarly to that of compound 5. In fact, we detected expected NOE interactions H-9 (δH 2.74, br t (4.6))/CH3-19 (δH 1.14, s); H-5 (δH 1.39, dd (12.7; 3.0))/Ha-11 (δH 2.48, dd (18.1, 5.4)) and Hb-11 (δH 2.38, dd (18.1, 4.8))/CH3-30 (δH 1.12, s). Therefore, derivatives 5 and 6 possess the same stereochemistry as other co-isolated isomalabaricanes. Although compounds 5 and 6 are rather artificial products derived during EtOH extraction, the isolated pair of esters allowed to reliably establish the position of the ether group based on the chemical shifts of C-12 and C-13.
Both compounds were supposed to be the half-ester derivatives of the hypothetical dicarboxylic acid. The anhydrous form of the acid was reported by Ravi et al. [5] as a product of ozonolysis of isomalabaricane precursor [22,23]. Moreover, Ravi et al. obtained dimethyl and monomethyl esters of the acid and did not point the place of esterification in the case of the latter.
Among isolated new compounds 1–6, we find stellettin S (3) the most intriguing, since occurrences of acetylene-containing isoprenoids are rare and not so far reported in the isomalabaricane series. To date, several biosynthetic pathways leading to the alkyne formation in natural products has been supported with identified and characterized gene clusters. In the first case, acetylenases, a special family of desaturases, catalyze the dehydrogenation of olefinic bonds in unsaturated fatty acids to afford acetylenic functionalities [24,25]. Next, acetylenases are also used to form the terminal alkyne in polyketides [26]. One more biosynthetic route results in a terminal alkyne formation in acetylenic amino acids and involves consequent transformations by halogenase BesD, oxidase BesC and lyase BesB [27]. Finally, two recent papers describe the molecular basis for the formation of alkyne moiety in acetylenic prenyl chains occurring in a number of meroterpenoids [28,29]. The abovementioned reports highlight hot trends in a scientific search for enzymatic machineries leading to the biologically significant and synthetically applicable acetylene bond in natural compounds. We believe that isolation of the new terpenoidal alkyne 3 could inspire further investigations of the Stelletta spp. sponges and associated microorganisms through genome mining.
According to obtained new data we also report the correction in stereochemistry of two asymmetric centers in globostelletins M (Figure S70) and N (Figure S71). Really, their ECD and NMR spectra in comparison with those of globostelletin K and stellettins Q and R (Figures S59–S71) clearly show rather 15R,23S configuration for globostelletin M instead of previously reported 15S,23S [15] as well as 15S,23R stereochemistry for globostelletin N instead of 15R,23R [15].

3. Materials and Methods

3.1. General Experimental Procedures

Optical rotations were measured on Perkin-Elmer 343 digital polarimeter (Perkin Elmer, Waltham, MA, USA). UV-spectra were registered on a Shimadzu UV-1601PC spectrophotometer (Shimadzu Corporation, Kyoto, Japan). ECD spectra were obtained on a Chirascan plus instrument (Applied Photophysics Ltd., Leatherhead, UK). 1H-NMR (500.13 MHz, 700.13 MHz) and 13C-NMR (125.75 MHz, 176.04 MHz) spectra were recorded in CDCl3 on Bruker Avance III HD 500 and Bruker Avance III 700 spectrometers (Bruker BioSpin, Bremen, Germany). The 1H- and 13C-NMR chemical shifts were referenced to the solvent peaks at δH 7.26 and δC 77.0 for CDCl3. HRESIMS analyses were performed using a Bruker Impact II Q-TOF mass spectrometer (Bruker). The operating parameters for ESI were as follows: a capillary voltage of 3.5 kV, nebulization witH-Nitrogen at 0.8 bar, dry gas flow of 7 L/min at a temperature of 200 °C. The mass spectra were recorded within m/z mass range of 100–1500. The instrument was operated using the otofControl (ver. 4.1, Bruker Daltonics) and data were analyzed using the DataAnalysis Software (ver. 4.4, Bruker Daltonics). Column chromatography was performed on Sephadex LH-20 (25–100 µm, Pharmacia Fine Chemicals AB, Uppsala, Sweden), silica gel (KSK, 50–160 mesh, Sorbfil, Krasnodar, Russia) and YMC ODS-A (12 nm, S-75 um, YMC Co., Ishikawa, Japan). HPLC were carried out using an Agilent 1100 Series chromatograph equipped with a differential refractometer (Agilent Technologies, Santa Clara, CA, USA). The reversed-phase columns YMC-Pack ODS-A (YMC Co., Ishikawa, Japan, 10 mm × 250 mm, 5 µm and 4.6 mm × 250 mm, 5 µm) and Discovery HS F5-5 (SUPELCO Analytical, Bellfonte, PA, USA, 10 mm × 250 mm, 5 µm) were used for HPLC. Yields are based on dry weight (212.1 g) of the sponge sample.

3.2. Animal Material

The Stelletta sp. sponge sample (wet weight 1.3 kg) was collected by SCUBA diving at the depth of 7–12 m near Cham Island (15°54.3′ N, 108°31.9′ E) in the Vietnamese waters of the South China Sea during the 038-th cruise of R/V “Academik Oparin” in May 2010. The species was identified and described [14] by Dr. Boris B. Grebnev from G. B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS (PIBOC, Vladivostok, Russia). A voucher specimen (PIBOC O38-301) has been deposited at the collection of marine invertebrates in PIBOC.

3.3. Extraction and Isolation

The frozen sponge was chopped and extracted with EtOH (1.7 L × 3) (Figure S73). The EtOH soluble materials (52.5 g) were concentrated, dissolved in distilled H2O (100 mL) and partitioned in turn with EtOAc (100 mL × 3). The EtOAc extracts were concentrated to a dark brown gum (15.7 g) that was further separated on a Sephadex LH-20 column (2 × 95 cm, CHCl3/EtOH, 1:1) to yield three fractions. Fraction 2 (10.2 g) was separated into nine subfractions using step-wise gradient silica gel column chromatography (4 × 15 cm, CHCl3→EtOH). Subfraction 2.4 (3.4 g) eluted with CHCl3/EtOH (80:1–10:1) was subjected to a silica gel column (4 × 15 cm, CHCl3/EtOH, 100:1→10:1) to obtain four subfractions. The fourth subfraction 2.4.4 (255.5 mg) was subjected to reversed-phase HPLC (YMC-Pack ODS-A, 70% EtOH) to give four subsubfractions (2.4.4.1-4) that were subjected to rechromatography. The HPLC fractionation of 2.4.4.1 (YMC-Pack ODS-A, 60% EtOH) gave cyclobutastellettolide A (7.7 mg, 0.004%), mixtures of globostelletins E+F (~2:1; 4.0 mg, 0.002%), K (3.4 mg, 0.002%), and M (1.7 mg, 0.002%), that were purified by HPLC procedures (Discovery HS F5-5, 60% EtOH), as it was reported previously [14]. One more component of this subsubfraction was purified (Discovery HS F5-5, 60% EtOH) to yield stellettin V (6, 2.6 mg, 0.001%). The subsubfraction 2.4.4.2, subjected to HPLC (Discovery HS F5-5, 70% EtOH) gave cyclobutastellettolide B [14] (1.6 mg, 0.004%) and stellettin T (4, 1.2 mg, 0.0006%), purified by HPLC (Discovery HS F5-5, 70% EtOH). The subsubfraction 2.4.4.3 contained cyclobutastellettolide B (1.4 mg) and stellettin Q (1, 0.9 mg, 0.0008%) isolated using reversed-phase HPLC (Discovery HS F5-5, 70% EtOH). The third subfraction 2.4.3 (641.5 mg) was divided four times (~160 mg × 4) using reversed-phase column chromatography (1 × 5 cm, YMC-Pack ODS-A, 50% EtOH and 100% EtOH) to yeild two subsubfractions. The subsubfraction eluted with 50% EtOH was separated by HPLC (YMC-Pack ODS-A, 70% EtOH) to afford a number of compounds and mixes for further purification. Then, stellettin U (5, 10.3 mg, 0.005%) as well as globostelletins N (9.2 mg, 0.004%) and M (1.5 mg) were isolated by HPLC (Discovery HS F5-5) in 80% MeOH. The HPLC procedures (Discovery HS F5-5) in 80% EtOH were used to obtain individual stellettins R (2, 2.1 mg, 0.001%), S (3, 6.9 mg, 0.003%) and portion of stellettin Q (1, 0.9 mg) that was purified by HPLC (Discovery HS F5-5) rechromatography in 65% CH3CN. Finally, one more portion of cyclobutastellettolide B (5.0 mg) was obtained from the subfraction by HPLC (Discovery HS F5-5) in 85% MeOH.

3.4. Compound Characteristics

Stellettin Q (1): Yellow oil; [α]D25–65.0 (c 0.1, CHCl3); ECD (c 8.6 × 10−4 M, EtOH) λmax (Δε) 195 (4.15), 229 (−27.92), 262 (12.78), 355 (−1.75) nm; 1H- and 13C-NMR data (CDCl3), Table 1; HRESIMS m/z 523.3065 [M–H]− (calcd for C32H43O6 523.3065).
Stellettin R (2): Yellow oil; [α]D25–24.0 (c 0.2, CHCl3); ECD (c 1.3 × 10−3 M, EtOH) λmax (Δε) 195 (4.06), 229 (−5.33), 252 (1.46), 273 (−0.48), 295 (0.47), 353 (−1.20) nm; 1H- and 13C- NMR data (CDCl3), Table 1; HRESIMS m/z 523.3068 [M–H]− (calcd for C32H43O6 523.3065).
Stellettin S (3): Slightly yellow oil; [α]D25 + 31.5 (c 0.2, CHCl3); ECD (c 5.3 × 10−3 M, EtOH) λmax (Δε) 289 (0.34), 321 (−0.14) nm; 1H- and 13C-NMR data (CDCl3), Table 2; HRESIMS m/z 303.1966 [M–H]− (calcd for C19H27O3 303.1966).
Stellettin T (4): Slightly yellow oil; [α]D25–22.0 (c 0.1, CHCl3); ECD (c 3.4 × 10−3 M, EtOH) λmax (Δε) 208 (−0.98), 249 (0.58), 280 (−0.27), 321 (−0.29) nm; 1H- and 13C-NMR data (CDCl3), Table 2; HRESIMS m/z 351.2176 [M–H]− (calcd for C20H31O5 351.2177).
Stellettin U (5): Slightly yellow oil; [α]D25 0.0 (c 0.2, CHCl3); ECD (c 5.7 × 10−3 M, EtOH) λmax (Δε) 197 (−0.73), 232 (0.27), 261 (0.45), 295 (0.01), 321 (−0.34) nm; 1H- and 13C-NMR data (CDCl3), Table 2; HRESIMS m/z 337.2022 [M–H]− (calcd for C19H29O5 337.2020).
Stellettin V (6): Slightly yellow oil; [α]D25 + 32.9 (c 0.17, CHCl3); ECD (c 7.7 × 10−3 M, EtOH) λmax (Δε) 210 (−0.04), 220 (0.08), 238 (−0.23), 269 (0.38), 291 (0.26), 330 (0.13), 357 (−0.09) nm; 1H- and 13C-NMR data (CDCl3), Table 2; HRESIMS m/z 337.2025 [M–H]− (calcd for C19H29O5 337.2020).
Globostelletin N (Figure 1): Slightly yellow oil; [α]D25 + 17.8 (c 0.23, MeOH); ECD (c 1.2 × 10−3 M, EtOH) λmax (Δε) 196 (−4.18), 228 (9.44), 256 (−1.72), 289 (0.97), 340 (−1.97) nm; 1H- and 13C-NMR spectra (CDCl3) corresponded to previously reported data [15] (Figures S62–S64); HRESIMS m/z 479.2808 [M–H]− (calcd for C30H39O5 479.2803).

4. Conclusions

To summarize, the present report describes the isolation and structural elucidation of six metabolites 1–6 from a tropical marine sponge belonging the genus Stelletta. A combination of NMR methods, supported with computational quantum-chemical modeling allowed us to establish the structures and absolute stereochemistry of two isomalabaricanes 1 and 2, while the structures and configurations of four isomalabaricane-derived terpenoids 3–6 were suggested on the basis of spectral data and biogenetic considerations. Stellettin S (3) represents the first acetylene-containing isomalabaricane-related compound. Additionally, according to new data the absolute stereochemistry of the C-15 and C-23 asymmetric centers of known globostelletins M and N were corrected.

Supplementary Materials

The following are available online. Figure S1: article title, authors affiliations and contact information, Figure S2: contents of Supplementary Materials, Figures S3–S10: HRESIMS, 1H- and 13C-NMR, HSQC, HMBC, COSY, ROESY spectra (CDCl3, 700 MHz) and ECD spectrum (EtOH) of stellettin Q (1), respectively, Figures S11–S18: HRESIMS, 1H- and 13C-NMR, HSQC, HMBC, COSY, ROESY spectra (CDCl3, 500 MHz) and ECD spectrum (EtOH) of stellettin R (2), respectively, Figures S19–S27: HRESIMS, 1H- and 13C-NMR, DEPT, HSQC, HMBC, COSY, ROESY spectra (CDCl3, 700 MHz) and ECD spectrum (EtOH) of stellettin S (3), respectively, Figures S28–S35: HRESIMS, 1H- and 13C-NMR, HSQC, HMBC, COSY, ROESY spectra (CDCl3, 700 MHz) and ECD spectrum (EtOH) of stellettin T (4), respectively, Figures S36–S44: HRESIMS, 1H- and 13C-NMR, DEPT, HSQC, HMBC, COSY, ROESY spectra (CDCl3, 700 MHz) and ECD spectrum (EtOH) of stellettin U (5), respectively, Figures S45–S53: HRESIMS, 1H- and 13C-NMR, DEPT, HSQC, HMBC, COSY, ROESY spectra (CDCl3, 700 MHz) and ECD spectrum (EtOH) of stellettin V (6), respectively, Figures S54–S57: HRESIMS, 1H- and 13C-NMR spectra (CDCl3) and ECD spectrum (EtOH) of globostelletin K, respectively, Figures S58–S61: HRESIMS, 1H- and 13C-NMR spectra (CDCl3) and ECD spectrum (EtOH) of globostelletin M, Figures S62–S65: HRESIMS, 1H and 13C NMR spectra (CDCl3) and ECD spectrum (EtOH) of globostelletin N, respectively, Figure S66: theoretical modeling details, Figures S67 and S68: optimized geometries and statistical weights of main and minor conformations of stellettin Q (1) and stellettin R (2), respectively, Figures S69–S71: the computational ECD results for globostelletins K, M and N, respectively. Figure S72: the computational ECD results calculated for all possible 15,23-stereoisomers of studied globostelletins K, M, N, and new stellettins Q (1) and R (2), Figure S73: the isolation scheme.

Author Contributions

Conceptualization, S.A.K., E.G.L.; methodology, S.A.K. and E.G.L.; formal analysis, S.A.K., E.G.L. and D.V.B.; investigation, S.A.K., E.G.L. and A.B.K.; data curation S.A.K. and E.G.L.; writing—original draft preparation, S.A.K. and E.G.L.; writing—review and editing, S.A.K., E.G.L. and V.A.S.; visualization, S.A.K. and E.G.L.; NMR data providing, A.I.K.; HRESI MS spectra acquisition and interpretation, R.S.P.; supervision, V.A.S.; project administration, V.A.S.; funding acquisition, V.A.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the RSF (Russian Science Foundation), grant number 20-14-00040.

Acknowledgments

The study was carried out on the equipment of the Collective Facilities Center “The Far Eastern Center for Structural Molecular Research (NMR/ MS) of PIBOC FEB RAS”. Authors thank the Vietnamese Academy of Science and Technology for collaboration and participation in prеvious joint publication [14].

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Samples of the compounds are available from the authors.

References

  1. Chawla, A.; Dev, S. A new class of triterpenoids from Ailanthus malabarica DC derivatives of malabaricane. Tetrahedron Lett. 1967, 8, 4837–4843. [Google Scholar] [CrossRef]
  2. Ziegler, H.L.; Stærk, D.; Christensen, J.; Olsen, C.E.; Sittie, A.A.; Jaroszewsky, J.W. New dammarane and malabaricane triterpenes from Caloncoba echinata. J. Nat. Prod. 2002, 65, 1764–1768. [Google Scholar] [CrossRef] [PubMed]
  3. Achanta, P.S.; Gattu, R.K.; Belvotagi, A.R.V.; Akkinepally, R.R.; Bobbala, R.K.; Achanta, A.R.V.N. New malabaricane triterpenes from the oleoresin of Ailanthus malabarica. Fitoterapia 2015, 100, 166–173. [Google Scholar] [CrossRef]
  4. Ebada, S.S.; Lin, W.; Proksch, P. Bioactive sesterterpenes and triterpenes from marine sponges: Occurrence and pharmacological significance. Mar. Drugs 2010, 8, 313–346. [Google Scholar] [CrossRef] [Green Version]
  5. Ravi, B.N.; Wells, R.J.; Croft, K.D. Malabaricane triterpenes from a Fijian collection of the sponge Jaspis stellifera. J. Org. Chem. 1981, 46, 1998–2001. [Google Scholar] [CrossRef]
  6. Wu, Q.; Nay, B.; Yang, M.; Ni, Y.; Wang, H.; Yao, L.; Li, X. Marine sponges of the genus Stelletta as promising drug sources: Chemical and biological aspects. Acta Pharm. Sin. B. 2019, 9, 237–257. [Google Scholar] [CrossRef] [PubMed]
  7. Li, Y.; Tang, H.; Tian, X.; Lin, H.; Wang, M.; Yao, M. Three new cytotoxic isomalabaricane triterpenes from the marine sponge Stelletta tenuis. Fitoterapia 2015, 106, 226–230. [Google Scholar] [CrossRef] [PubMed]
  8. Barrero, A.F.; Oltra, J.E.; Herrador, M.M.; Cabrera, E.; Sanchez, J.F.; Quílez, J.F.; Rojas, F.J.; Reyes, J.F. Gibepyrones: α-pyrones from Gibberella fujikuroi. Tetrahedron 1993, 49, 141–150. [Google Scholar] [CrossRef]
  9. Tang, S.; Xu, R.; Lin, W.; Duan, H. Jaspiferin A and B: Two new secondary metabolites from the South China sea sponge Jaspis stellifera. Rec. Nat. Prod. 2012, 6, 398–401. [Google Scholar]
  10. Dung, D.T.; Hang, D.T.T.; Nhiem, N.X.; Quang, T.H.; Tai, B.H.; Yen, P.H.; Hoai, N.T.; Thung, D.C.; Minh, C.V.; Kiem, P.V. Rhabdaprovidines D–G, four new 6,6,5-tricyclic terpenoids from the Vietnamese sponge Rhabdastrella providentiae. Nat. Prod. Commun. 2018, 13, 1251–1254. [Google Scholar] [CrossRef]
  11. Kiem, P.V.; Dung, D.T.; Yen, P.H.; Nhiem, N.X.; Quang, T.H.; Tai, B.H.; Minh, C.V. New isomalabaricane analogues from the sponge Rhabdastrella providentiae and their cytotoxic activities. Phytochem. Lett. 2018, 26, 199–204. [Google Scholar] [CrossRef]
  12. Tang, S.; Pei, Y.; Fu, H.; Deng, Z.; Li, J.; Proksch, P.; Lin, W. Jaspolides A–F, six new isomalabricane-type terpenoids from the sponge Jaspis sp. Chem. Pharm. Bull. 2006, 54, 4–8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Li, J.; Xu, B.; Cui, J.; Deng, Z.; de Voogd, N.J.; Proksch, P.; Lin, W. Globostelletins A–I, cytotoxic isomalabaricane derivatives from the marine sponge Rhabdastrella globostellata. Bioorg. Med. Chem. 2010, 18, 4639–4647. [Google Scholar] [CrossRef] [PubMed]
  14. Kolesnikova, S.A.; Lyakhova, E.G.; Kalinovsky, A.I.; Berdyshev, D.V.; Pislyagin, E.A.; Popov, R.S.; Grebnev, B.B.; Makarieva, T.N.; Minh, C.V.; Stonik, V.A. Cyclobutastellettolides A and B, C19 norterpenoids from a Stelletta sp. marine sponge. J. Nat. Prod. 2019, 82, 3196–3200. [Google Scholar] [CrossRef] [PubMed]
  15. Li, J.; Zhu, H.; Ren, J.; Deng, Z.; de Voogd, N.J.; Proksch, P.; Lin, W. Globostelletins J–S, isomalabaricanes with unusual cyclopentane sidechains from the marine sponge Rhabdastrella globostellata. Tetrahedron 2012, 68, 559–565. [Google Scholar] [CrossRef]
  16. Stephens, P.J.; Devlin, F.J.; Chabalowski, C.F.; Frisch, M.J. Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J. Phys. Chem. 1994, 98, 11623–11627. [Google Scholar] [CrossRef]
  17. Miertuš, S.; Scrocco, E.; Tomasi, J. Electrostatic interaction of a solute with a continuum. A direct utilizaion of ab initio molecular potentials for the prevision of solvent effects. Chem. Phys. 1981, 55, 117–129. [Google Scholar] [CrossRef]
  18. Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; et al. Gaussian 16; Revision B.01.; Gaussian, Inc.: Wallingford, CT, USA, 2016. [Google Scholar]
  19. Ryu, G.; Matsunaga, S.; Fusetani, N. Globostellatic Acids A−D, new cytotoxic isomalabaricane triterpenes from the marine sponge Stelletta globostellata. J. Nat. Prod. 1996, 59, 512–514. [Google Scholar] [CrossRef]
  20. Zampella, A.; D’Auria, M.V.; Debitus, C.; Menou, J.-L. New isomalabaricane derivatives from a new species of Jaspis sponge collected at the Vanuatu islands. J. Nat. Prod. 2000, 63, 943–946. [Google Scholar] [CrossRef]
  21. Deng, J.; Wu, J.; Tian, H.; Bao, J.; Shi, Y.; Tian, W.; Gui, J. Alkynes from furans: A general fragmentation method applied to the synthesis of the proposed structure of aglatomin B. Angew. Chem. 2018, 57, 3617–3621. [Google Scholar] [CrossRef]
  22. McCabe, T.; Clardy, J.; Minale, L.; Pizza, C.; Zollo, F.; Riccio, R. A triterpenoid pigment with the isomalabaricane skeleton from the marine sponge Stelletta sp. Tetrahedron Lett. 1982, 23, 3307–3310. [Google Scholar] [CrossRef]
  23. McCormick, J.L.; McKee, T.C.; Cardellina, J.H.; Leid, M.; Boyd, M.R. Cytotoxic triterpenes from a marine sponge, Stelletta sp. J. Nat. Prod. 1996, 59, 1047–1050. [Google Scholar] [CrossRef]
  24. Lee, M. Identification of non-heme diiron proteins that catalyze triple bond and epoxy group formation. Science 1998, 280, 915–918. [Google Scholar] [CrossRef] [PubMed]
  25. Jeon, J.E.; Kim, J.-G.; Fischer, C.R.; Mehta, N.; Dufour-Schroif, C.; Wemmer, K.; Mudgett, M.B.; Sattely, E. A pathogen-responsive gene cluster for highly modified fatty acids in tomato. Cell 2020, 180, 176–187. [Google Scholar] [CrossRef] [PubMed]
  26. Zhu, X.; Liu, J.; Zhang, W. De novo biosynthesis of terminal alkyne-labeled natural products. Nat. Chem. Biol. 2015, 11, 115–120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  27. Marchand, J.A.; Neugebauer, M.E.; Ing, M.C.; Lin, C.-I.; Pelton, J.G.; Chang, M.C.Y. Discovery of a pathway for terminal-alkyne amino acid biosynthesis. Nature 2019, 567, 420–424. [Google Scholar] [CrossRef]
  28. Chen, Y.; Naresh, A.; Liang, S.; Lin, C.; Chein, R.; Lin, H. Discovery of a dual function cytochrome P450 that catalyzes enyne formation in cyclohexanoid terpenoid biosynthesis. Angew. Chem. 2020, 59, 13537–13541. [Google Scholar] [CrossRef]
  29. Lv, J.; Gao, Y.; Zhao, H.; Awakawa, T.; Liu, L.; Chen, G.; Yao, X.; Hu, D.; Abe, I.; Gao, H. Biosynthesis of biscognienyne B involving a cytochrome P450-dependent alkynylation. Angew. Chem. 2020, 59, 13531–13536. [Google Scholar] [CrossRef]
Molecules 26 00678 g001 550
Figure 1. Structures of compounds 1–6 and globostelletins K, M, and N.
Figure 1. Structures of compounds 1–6 and globostelletins K, M, and N.
Molecules 26 00678 g001
Molecules 26 00678 g002 550
Figure 2. Selected COSY ( Molecules 26 00678 i001), HMBC ( Molecules 26 00678 i002) and ROESY ( Molecules 26 00678 i003) correlations of 1 and 2.
Figure 2. Selected COSY ( Molecules 26 00678 i001), HMBC ( Molecules 26 00678 i002) and ROESY ( Molecules 26 00678 i003) correlations of 1 and 2.
Molecules 26 00678 g002
Molecules 26 00678 g003 550
Figure 3. Comparison of experimental and theoretical ECD spectra of stellettin Q (1).
Figure 3. Comparison of experimental and theoretical ECD spectra of stellettin Q (1).
Molecules 26 00678 g003
Molecules 26 00678 g004 550
Figure 4. Comparison of experimental and theoretical ECD spectra of stellettin R (2).
Figure 4. Comparison of experimental and theoretical ECD spectra of stellettin R (2).
Molecules 26 00678 g004
Molecules 26 00678 g005 550
Figure 5. Selected COSY ( Molecules 26 00678 i001) and HMBC ( Molecules 26 00678 i002) correlations of 3 and 4 and structure of known globostelletin A.
Figure 5. Selected COSY ( Molecules 26 00678 i001) and HMBC ( Molecules 26 00678 i002) correlations of 3 and 4 and structure of known globostelletin A.
Molecules 26 00678 g005
Molecules 26 00678 g006 550
Figure 6. Selected ROESY ( Molecules 26 00678 i003) correlations of 3.
Figure 6. Selected ROESY ( Molecules 26 00678 i003) correlations of 3.
Molecules 26 00678 g006
Molecules 26 00678 g007 550
Figure 7. Selected COSY ( Molecules 26 00678 i001) and HMBC ( Molecules 26 00678 i002) correlations of 5 and 6.
Figure 7. Selected COSY ( Molecules 26 00678 i001) and HMBC ( Molecules 26 00678 i002) correlations of 5 and 6.
Molecules 26 00678 g007
Table
Table 1. 1H and 13C NMR data of 1 (700 and 176 MHz) and 2 (500 and 126 MHz) in CDCl3.
Table 1. 1H and 13C NMR data of 1 (700 and 176 MHz) and 2 (500 and 126 MHz) in CDCl3.
No. 112
δH mult (J in Hz)δCδH mult (J in Hz)δC
1α1.57, td (13.0, 3.9)33.11.57, m32.9
1β1.38, m1.36, m
2α1.82, m25.11.81, m25.1
2β1.71, m1.68, m
3α4.54, dd (11.7, 5.2)80.84.53, dd (11.6, 5.2)80.7
4 38.2 38.2
5α1.73, m46.51.75, m46.4
6α1.70, m18.21.68, m18.2
6β1.48, m1.48, m
7α1.99, m37.72.06, m38.5
7β2.00, m1.93, m
8 44.2 43.8
9β1.75, m50.31.77, m50.3
10 35.4 35.4
11α2.13, m36.42.15, m36.4
11β2.13, m2.15, m
12 206.6 206.9
13 146.8 146.0
14 147.9 147.5
154.75, m45.0 23.22, dt (9.2, 6.0)48.0
16α2.27, m37.92.52, m38.4
16β3.02, ddt (19.4, 9.3, 2.5)2,89, ddt (19.4, 9.2, 2.7)
176.80, br s144.66.78, dd (4.3, 2.5)143.6
181.79, s16.2 22.06, s15.7
191.02, s22.41.01, s22.4
20 195.6 195.1
212.29, s26.92.30, s27.0
22 146.6 146.7
233.86, br t (8.3)47.53.95, m48.0
246.57, br d (10.2)145.96.59, dd (10.6, 1.5)144.6
25 126.3 127.3
26 171.0 170.7
271.88, br s12.61.86, d (1.3)12.5
280.91, s29.00.90, s29.0
290.89, s16.90.88, s17.0
301.29, s24.11.23, s26.4
OAc2.06, s171.021.22.05, s170.921.2
1 Assignments were made with the aid of HSQC, HMBC and ROESY data. 2 The values were found from HSQC experiment.
Table
Table 2. 1H and 13C NMR data (700 and 176 MHz) of 3–6 in CDCl3.
Table 2. 1H and 13C NMR data (700 and 176 MHz) of 3–6 in CDCl3.
No. 13456
δH mult (J in Hz)δCδH mult (J in Hz)δCδH mult (J in Hz)δCδH mult (J in Hz)δC
1α1.76, m35.91.33, m34.31.78, m35.51.79, m35.6
1β1.57, ddd (13.3, 6.3, 3.7)1.28, m1.57, ddd (13.5, 6.0, 4.0)1.60, m
2α2.33, m34.81.72, m23.32.31, m34,82.32, dt (15.4, 4.5)34.8
2β2.70, ddd (15.6, 12.3, 6.4)1.68, m2.65, ddd (15.4, 12.6, 6.1)2.66, ddd (15.4, 12.6, 6.1)
3 216.5α: 4.44, dd (11.2, 5.1)80.3 216.1 216.0
4 47.7 37.6 47.5 47.5
5α1.33, dd (12.4, 2.7)47.51.01, dd (11.9; 2.7)46.21.40, dd (12.6; 3.0)46.71.39, dd (12.7; 3.0)46.8
6α1.47, dq (13.6, 3.2)21.11.65, m17.91.46, m20.41.47, m20.5
6β1.83, qd (13.2, 3.4)1.47, m1.79, m1.78, m
7α1.25, td (13.2, 3.7)36.51.51, m30.01.11, m31.21.08, m31.5
7β1.74, m1.59, m2.20, br d (15.1)2.23, br d (14.2)
8 34.1 52.5 44.5 44.5
9β2.22, t (5.1)51.22.31 br d (8.0)49.42.78 br t (5.0)48.32.74 br t (4.6)48.3
10 38.5 38.6 38.5 38.4
11a2.40, dd (18.1, 5.8)31.12.58, dd (18.9, 7.9)34.12.41, dd (17.7, 5.3)31.12.48, dd (18.1, 5.4)30.5
11b2.33, dd (17.7, 4.8)1.70, br d (18.9)2.30, m2.38, dd (18.1, 4.8)
12 178.8 175.2 2 173.7 177.6 3
13 88.1 213.0 183.8 178.0 3
14 77.82.12, s24.7
15–17
181.80, s3.7
191.62, s23.31.27, s24.61.24, s20.81.14, s20.7
20–27
281.08, s25.90.89, s27.91.07, s25.71.07, s25.7
291.06, s21.60.87, s16.21.00, s21.50.99, s21.5
301.25, s30.81.31,s24.61.17, s27.81.12, s27.7
OAc 2.05, s170.9
21.2
OEt 4.15, q (7.1), 2H,
1.26, t (7.1), 3H		60.8
14.1		4.23, dq (10.9, 7.1), H
4.13, dq (10.9, 7.1), H
1.31, t (7.1), 3H		60.6
14.0
1 Assignments were made with the aid of HSQC, HMBC and ROESY data. 2 The values were found from HMBC experiment. 3 These signals could be interchanged.
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Kolesnikova, S.A.; Lyakhova, E.G.; Kozhushnaya, A.B.; Kalinovsky, A.I.; Berdyshev, D.V.; Popov, R.S.; Stonik, V.A. New Isomalabaricane-Derived Metabolites from a Stelletta sp. Marine Sponge. Molecules 2021, 26, 678. https://doi.org/10.3390/molecules26030678

AMA Style

Kolesnikova SA, Lyakhova EG, Kozhushnaya AB, Kalinovsky AI, Berdyshev DV, Popov RS, Stonik VA. New Isomalabaricane-Derived Metabolites from a Stelletta sp. Marine Sponge. Molecules. 2021; 26(3):678. https://doi.org/10.3390/molecules26030678

Chicago/Turabian Style

Kolesnikova, Sophia A., Ekaterina G. Lyakhova, Anastasia B. Kozhushnaya, Anatoly I. Kalinovsky, Dmitrii V. Berdyshev, Roman S. Popov, and Valentin A. Stonik. 2021. "New Isomalabaricane-Derived Metabolites from a Stelletta sp. Marine Sponge" Molecules 26, no. 3: 678. https://doi.org/10.3390/molecules26030678

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