Chemistry of renieramycins. Part 7: Renieramycins T and U, novel renieramycin-ecteinascidin hybrid marine natural products from Thai sponge Xestospongia sp.

Two new bistetrahydroisoquinoline marine natural products, renieramycins T (1) and U (2), were isolated from the Thai blue sponge Xestospongia sp. and their structures were elucidated by comparing spectral data with those of renieramycin M (3a) and ecteinascidin 770 (4a). These compounds are the first reported examples of novel ecteinascidin-renieramycin hybrid natural products. Renieramycin T (1) showed strong cytotoxicity to several human cancer cell lines, its IC₅₀ values ranging from 4.7 to 98 nM.     

Chemistry of renieramycins. Part 6: Transformation of renieramycin M into jorumycin and renieramycin J including oxidative degradation products, mimosamycin, renierone, and renierol acetate

The transformation of renieramycin M (1m) into renieramycin J (1j) and jorumycin (2) is presented along with the results of antiproliferative assay data. The chemical stability and the oxidative degradation of 2 and renieramycin E (1e) to generate simple isoquinoline alkaloids, such as mimosamycin (7), renierol acetate (12), and renierone (8) are also described.     

Jorunnamycins A-C, new stabilized renieramycin-type bistetrahydroisoquinolines isolated from the Thai nudibranch Jorunna funebris

Jorunnamycins A-C (1a-c), three stabilized renieramycin-type bistetrahydroisoquinolines, were isolated from the mantles, the visceral organs, and the egg ribbons of the Thai nudibranch Jorunna funebris that was pretreated with potassium cyanide (KCN), along with five known compounds, renieramycins M (2m), N (2n), O (2o), and Q (2q) and mimosamycin (3). The structures of 1a-c were elucidated from spectroscopic data and by chemical conversion of renieramycin M (2m) into 1c via 1a. The chemical stability and the oxidative degradation generating simple isoquinoline alkaloids of a carbinolamine analog 1d, which was easily prepared by reacting 1c with silver nitrate in aqueous acetonitrile, are discussed. The results of cytotoxicity studies are also presented.     

Chemistry of ecteinascidins. Part 2. Preparation of 6'-O-acyl derivatives of stable ecteinascidin and evaluation of cytotoxicity

A large amount of stable ecteinascidin 770 (1b) was isolated from the Thai tunicate, Ecteinascidia thurstoni, which was pretreated with potassium cyanide in buffer solution (pH 7), along with a minor metabolite, ecteinascidin 786 (1c). A number of 6'-O-acyl derivatives 3-19 and three diacetyl derivatives 2a-c of the stable 1b were prepared and evaluated for activity against human tumor cell lines HCT116, QG56, and DU145. Nitrogen-containing heterocyclic ester derivatives such as 12, 13, and 16-19 showed similar in vitro cytotoxicity to 1b, whereas the other derivatives were less cytotoxic than 1b. Furthermore, we discovered that the N-indole-3-carbonyl derivative of ecteinascidin 770 (22) has higher cytotoxicity than 1b.