Lamellarin Sulfates from the Pacific Tunicate Didemnum ternerratum

Abstract

Six new lamellarin sulfates (1–6) were isolated from the methanolic extract of the Pacific tunicate Didemnum ternerratum, collected from the Kingdom of Tonga. Mass spectrometric molecular networking through the GNPS platform was used to target the isolation of 1–6. Planar structures were elucidated through a combination of NMR and MS experiments. Through comparison of experimental and calculated ECD spectra, the absolute configurations of atropisomers 2–5 were determined, with their energetic barriers to racemization also determined computationally. The cytotoxicity of the compounds was tested against the human colon carcinoma cell line HCT-116, where lamellarin D-8-sulfate (5) exhibited moderate activity with an IC50 of 9.7 μM.

Crews' rule—Still useful but often misquoted

“…[1] Some authors, familiar with the contents of the original publication, have applied or quoted this correctly. [2][3][4][5][6][7] Unfortunately, the first easily located publication [8] using the term Crews' rule gives the critical H/C atom ratio as 2 rather than the value of 1 given in the original paper. This error has propagated through the literature [9][10][11][12][13][14][15][16][17][18] and continues to do so to this day.…”

Secondary Metabolites of the Genus Didemnum: A Comprehensive Review of Chemical Diversity and Pharmacological Properties

“…24(R)-methylcholest-6-en-3β-ol (38), 5α,8α-epidioxy-24(S)-ethylcholest-6-en-3β-ol (39), and 5α,8αepidioxy-24(R)-ethylcholest-6-en-3β-ol (40) [24]. Bromley and co-authors have reported two halogenated compounds from a South African unidentified Didemnum sp., namely 3,5dibromotetramethyltyrosine (41) and 3-iodotetramethyltyrosine (42) (Figure 8) [25].…”

“…Five 5α,8α-epidioxysterols derivatives were isolated from D. salary including 5α,8αepidioxycholest-6-en-3β-ol (36), 5α,8α-epidioxy-24(S)-methylcholest-6-en-3β-ol (37), 5α,8α-epidioxy-24(R)-methylcholest-6-en-3β-ol (38), 5α,8α-epidioxy-24(S)-ethylcholest-6-en-3β-ol (39), and 5α,8αepidioxy-24(R)-ethylcholest-6-en-3β-ol (40) [24].…”

“…Compounds with Antitumor/Anticancer and Antiproliferative Activities (Table S1) Numerous DOPA-derived pyrrole alkaloids have been reported from different members of the genus Didemnum, including the lamellarins. In 1999, lamellarins A, B, C, E, G, L, and Z (56-62) ( Figures 10 and 11) were isolated from the Australian D. chartaceum, along with 20-sulfated derivatives of lamellarins B, C, and L (63-65) ( Figures 10 and 11), the 8-sulfated derivative of lamellarin G (66) ( Figure 10) and the triacetyl derivatives of lamellarins D and N (67 and 68) ( Figure 11 [38].…”

Targeted Isolation of Rubrolides from the New Zealand Marine Tunicate Synoicum kuranui

“…As part of our continuing investigation of the secondary metabolites produced by marine invertebrates collected from the South Pacific [10][11][12][13], we recently reported the first study utilizing MN to examine the chemical constituents of various Tongan marine tunicates [14]. The major constellation of the network consisted of three linked clusters of nodes, and prioritization of the fractions containing lamellarin sulfates resulted in the characterization of the first new sulfated lamellarins reported in over 20 years [14]. Tunicates have been an excellent source of natural products to date, including the FDA-approved plitidepsin (Aplidin ® ) and trabectedin (Yondelis ® ); however, the number of new tunicate-derived compounds reported annually is decreasing, with 45% less reported in 2017 compared to 2016 [15].…”