Didemnins and Tunichlorin: Novel Natural Products from the Marine Tunicate Trididemnum solidum

Abstract

Didemnins A, B, and C, cyclic depsipeptides previously reported by our laboratory from the Caribbean tunicate Trididemnum solidum, have now been synthesized and, in the process, their structures have been revised to include the new amino acid (3S,4R,5S)-isostatine,C2H5CH(CH3)CHNH2CHOHCH2COOH. All other isomers of isostatine have also been prepared. Didemnin B is currently in Phase II clinical trials as an anticancer agent, and the antineoplastic activity, as well as the antiviral and immunosuppressive activities, of the didemnins are reviewed. A highly unusual porphynoid has also been isolated from T. solidum. The compound has been named tunichlorin and is apparently the first nickel-containing chlorin (and only the second nickel-containing porphyrin-related compound) identified from a living organism.

Molecular conformation of ascidiacyclamide, a cytotoxic cyclic peptide from Ascidian: X‐ray analyses of its free form and solvate crystals

“….37 (1) 3.31 (1) 3.31 (1) 3.25 (2) 3.33 (1) 3.34 (1) 3.39 (1) 3.04 (2) 3.19 (2) 3.38 (1) 3.37 (1) 01A …”

[Heavy metal]-Chlorophylls Formed in Vivo During Heavy Metal Stress and Degradation Products Formed During Digestion, Extraction and Storage of Plant Material

“…2), was found in the Caribbean tunicate, Trididemnum solidum (Bible et al, 1988;Rinehart et al, 1988), together with much Phe a and with didemnins (cytostatic natural products). Tunichlorin, unlike the Ni-porphyrin F430 of methanogenic bacteria (Pfaltz et al, 1982), currently has no proven physiological role (see below).…”

“…It decomposes rapidly even at low temperatures under N 2 (Bible et al, 1988), but its dimethyl derivative (Fig. 2), used in structural and spectral investigations (Bible et al, 1988;Rinehart et al, 1988;Andersson et al, 1990Andersson et al, , 1991Sings et al, 1996), is more stable.…”

“…It decomposes rapidly even at low temperatures under N 2 (Bible et al, 1988), but its dimethyl derivative (Fig. 2), used in structural and spectral investigations (Bible et al, 1988;Rinehart et al, 1988;Andersson et al, 1990Andersson et al, , 1991Sings et al, 1996), is more stable. The presence of Ni, suggested by mass spectrometry (MS) data, was confirmed by atomic absorption spectroscopy and by demetalation and remetalation experiments (Bible et al, 1988).…”

“…Since Trididemnum and Dolabella both coexist with algal endosymbionts, the biosynthetic origin of tunichlorin (Rinehart et al, 1988) is unclear: the biosynthesis of chlorin-type tetrapyrroles is restricted to photosynthetic organisms, but [Ni]-Chls have not been reported in free-living algae (Bible et al, 1988). Therefore, tunichlorin is probably derived from algal Chl by partial degradation and transmetalation in the animal.…”