Isolation and Structure of the Cell Growth Inhibitory Depsipeptides Dolastatins 11 and 12

(−)-Doliculide, a New Macrocyclic Depsipeptide Enhancer of Actin Assembly

“…7). DISCUSSION Doliculide, like dolastatin 11 (4), is a depsipeptide originally extracted from the sea hare D. auricularia (10), but the source organism was obtained from Pacific Ocean waters rather than from the Indian Ocean. We have shown here that doliculide, like dolastatin 11 (16), jasplakinolide (17), phalloidin (23,25), and chondramide A (19), enhances the assembly of purified actin, arrests cells at cytokinesis, and causes the accumulation of presumptive (based on the binding of FITC-phalloidin) F-actin aggregates in cells treated with the drug.…”

“…1 and 2 for reviews). Interestingly, structurally different molecules have been derived from Indian Ocean (for example, dolastatins 10 (3), 11 (4), and 15 (5)) and Pacific Ocean (for example, dolastatin G (6) and dolastatin H (7)) specimens of the organism, and it seems increasingly likely that these peptides and depsipeptides may actually derive from cyanobacteria that D. auricularia shelters or upon which it feeds (8,9). Although Yamada and co-workers (10 -12) described the isolation, cytotoxic activity, and synthesis of (Ϫ)-doliculide 1 (see structure in Fig.…”

Isolation and Structure Determination of Lyngbyastatin 3, a Lyngbyastatin 1 Homologue from the Marine Cyanobacterium Lyngbya majuscula. Determination of the Configuration of the 4-Amino-2,2-dimethyl-3-oxopentanoic Acid Unit in Majusculamide C, Dolastatin 12, Lyngbyastatin 1, and Lyngbyastatin 3 from Cyanobacteria

“…5 The structure determinations of these cyanobacterial samples were hampered by the extensive signal doubling and broadening observed in the NMR spectra, a phenomenon not seen in the NMR spectra of majusculamide C (4) 7d from cyanobacteria or the samples of dolastatin 11 (5) 8 and dolastatin 12 (3) 8 from the sea hare. On the basis of epimerization experiments on 4, we concluded that the unusual spectral broadness observed in the cyanobacterial samples of 2 and 3 was due to these samples being mixtures of diastereomers arising from epimerization of the acid-sensitive Ibu unit.…”

Toward the Total Synthesis of Onchidin, a Cytotoxic Cyclic Depsipeptide from a Mollusc

“…It was found that this type of a-methyl-bamino acid is a crucial component of many biologically active cyclic peptides of marine origin. Representative examples are nodularin [3] and microcystin, [4] which are notorious for their hepatotoxicity, and majusculA C H T U N G T R E N N U N G amide C, [5] dolastatin 11 and 12, [6] and kulokekahilide-1, [7] which are valued for their antifungal and antineoplastic activity.…”