An Economical Synthesis of Caulerpin and Evaluation of Its New Anticancer Activities

Abstract

Caulerpin was economically synthesized with a new easy‐handled procedure in higher overall yield of 25.4%, compared to overall yield of 11% in reported literature. Evaluation of caulerpin in new types of cancer cell lines was performed and generally excellent biological activities were observed. In which, caulerpin showed the most activity in human liver tumor cell line (Huh7: IC50 =0.7 μM).

Synthesis of the Octameric Ring Containing Compound Caulerpin Using a Knoevenagel Reaction Catalyzed by an Amino Acid ‐ Ionic Liquid Solvent

“…In Li's experiment, when Knoevenagel condensation between 1 a is about to proceed, formaldehyde group at C−3 position will always be activated by piperidine first, forming a nitrogenous base – substrates binding intermediate which is more susceptible to electron's attack. The special intermediate with m/z 285 (positive mode) was found in reaction system when it were refluxed 5 min [5c] . On the basis of this record, we considered two classic mechanism of KC reaction as we known, put tryptophan as the nitrogenous base into mechanism graph and inferred some intermediates‘ m/z peak signal.…”

“…We used the most up to date method to synthesise the intermediate methyl 2‐(3‐formyl‐1H‐indol‐2‐yl)acetate) by following two substitution reactions from indole [5c] . Thereafter the intermediates were dimerized by the intermolecular Knoevenagel reaction.…”

“…These substituted reactants or intermediates were synthesized first using Hangbin Li′s scheme. In the past, Hangbin Li failed to directly cyclize the 6‐substituted intermediates to produce 6,6’‐disubstituted caulerpin, while attempting to optimize the Canché Chay method, [5c] so in this experiment derivatives were designed to be substituted at the C−6 position for the purpose of novelty and to test the amino acid‐ionic liquid system. The results showed that catalysis with the amino acid‐ionic liquid system could directly obtain the 6,6’‐disubstituted caulerpin, although the yields were still low (23–31 %, see Table 2).…”

Anti-SARS-CoV-2 and cytotoxic activity of two marine alkaloids from green alga Caulerpa cylindracea Sonder in the Dardanelles

“…In this study, the cytotoxic activity of the extract of C. cylindracea , and two isolates caulerpin and monomethyl caulerpinate were also investigated against the aggressive breast cancer cell line MDA-MB-231 for the first time besides breast cell line MCF-7. In fact, in a previous studies, caulerpin was evaluated by Li et al against a panel of human cancer cell lines, and IC 50 values were found to be 4.67 (human leukemia: K562), 4.20 (human lung: A549), 1.95 (human cervical: HeLa), 4.04 (human colon: HT29), 3.71 (human breast: SK-BR-3), and 0.72 (human liver: Huh7) μM, 39 but not on MDA-MB-231 and MCF-7 breast cell lines.…”