Lyngbyabellin B, a toxic and antifungal secondary metabolite from the marine cyanobacterium Lyngbya majuscula

Lyngbyabellin B (1) was isolated from a marine cyanobacterium, Lyngbya majuscula, collected near the Dry Tortugas National Park, Florida. This new cyclic depsipeptide displayed potent toxicity toward brine shrimp and the fungus Candida albicans. The planar structure was deduced using 1D and 2D NMR spectroscopic methods, and the stereochemistry is proposed through a combination of NMR and chiral GC/MS analysis.     

Pitiprolamide, a proline-rich dolastatin 16 analogue from the marine cyanobacterium Lyngbya majuscula from Guam

An unusual cyclic depsipeptide, pitiprolamide (1), was isolated from the marine cyanobacterium Lyngbya majuscula collected at Piti Bomb Holes, Guam. The structure was deduced using NMR, MS, X-ray crystallography, and enantioselective HPLC-MS techniques. Remarkably, proline represents half of the residues forming pitiprolamide (1). Other distinctive features include a 4-phenylvaline (dolaphenvaline, Dpv) moiety initially found in dolastatin 16 and the rare 2,2-dimethyl-3-hydroxyhexanoic acid (Dmhha) unit condensed in a unique sequence in one single molecule. Pitiprolamide (1) showed weak cytotoxic activity against HCT116 colon and MCF7 breast cancer cell lines, as well as weak antibacterial activities against Mycobacterium tuberculosis and Bacillus cereus.     

Lyngbyastatin 2 and norlyngbyastatin 2, analogues of dolastatin G and nordolastatin G from the marine cyanobacterium Lyngbya majuscula

Lyngbyastatin 2 (1) and norlyngbyastatin 2 (2), new cytotoxic analogues of dolastatin G (3) and nordolastatin G (4), respectively, have been isolated as constituents from a Guamanian variety of the marine cyanobacterium Lyngbya majuscula. Structure elucidation of these cyclic depsipeptides relied on extensive application of 2D NMR techniques. The finding of these new metabolites further supports the proposal that many compounds originally isolated from the sea hare Dolabella auricularia are most likely of cyanobacterial origin.     

Ulongapeptin,a cytotoxic cyclic depsipeptide from a Palauan marine cyanobacterium Lyngbya sp

Ulongapeptin (1), a cyclic depsipeptide, was isolated from a Palauan marine cyanobacterium Lyngbya sp. The gross structure was elucidated through one-dimensional TOCSY experiments and other spectroscopic techniques. The absolute and relative stereochemistry of the beta-amino acid, 3-amino-2-methyl-7-octynoic acid (AMO), in 1 was determined by synthesis of the saturated alpha-alkyl-beta-amino acid and Marfey's analysis of the acid hydrolysate of tetrahydro-1. Ulongapeptin (1) was cytotoxic against KB cells at an IC(50) value of 0.63 microM.     

The guineamides,novel cyclic depsipeptides from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula

The guineamides (1-6) are novel cyclic depsipeptides isolated and characterized from a Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula. The planar structures of these new natural products were established using an extensive array of 1D and 2D NMR experiments, including HSQC, TOCSY, and HMBC. Absolute stereochemistry was determined using a combination of chemical manipulations as well as Marfey's method. These metabolites all contain beta-amino or beta-hydroxy carboxylic acid residues, an increasingly common feature in marine cyanobacterial metabolites. The identification of 2,2-dimethyl-3-hydroxyhexanoic acid (Dmhha) in guineamides E (5) and F (6) represents the first report of such a residue in a natural product. In addition, characterization of the unique beta-amino acid 2-methyl-3-aminopentanoic acid (Mapa) in guineamide A (1), which has also been reported as a component of several marine molluscan metabolites, especially from those of Dolabella auricularia, further supports the diet-derived nature of such compounds as isolated from marine invertebrates. Guineamides B (2) and C (3) possess moderate cytotoxicity to a mouse neuroblastoma cell line with IC(50) values of 15 and 16 microM, respectively.     

Tumonoic acids, novel metabolites from a cyanobacterial assemblage of Lyngbya majuscula and Schizothrix calcicola

Five new metabolites have been isolated from a lyngbyastatin 1- and dolastatin 12-producing assemblage of Lyngbya majuscula and Schizothrix calcicola collected at Tumon Bay, Guam. Structure elucidation employed 2D NMR techniques and chemical derivatization. These compounds have been assigned the trivial names tumonoic acids A (2), B (1), and C (5); methyl tumonoate A (3), and methyl tumonoate B (4). Compounds 1 and 4 were also found in a lyngbyastatin 1-producing strain of L. majuscula from Guam.     

Isolation of four new cyclic depsipeptides, antanapeptins A-D, and dolastatin 16 from a Madagascan collection of Lyngbya majuscula.

Examination of a Lyngbya majuscula collection from Antany Mora, Madagascar, led to the isolation of dolastatin 16 (5), a promising antineoplastic metabolite first reported from the marine mollusc Dolabella auricularia. In addition, a new series of depsipeptides, antanapeptins A-D (1-4), were discovered. Their structures were deduced by 2D NMR and mass spectrometry and are analogous to the molluscan kulomo'opunalides and the recently reported cyanobacterial metabolites, georgamide and the yanucamides. The antanapeptins were evaluated in several biological assays; however, this series did not exhibit activity.     

Isolation and structure determination of obyanamide, a novel cytotoxic cyclic depsipeptide from the marine cyanobacterium Lyngbya confervoides.

Obyanamide (1) was isolated from a variety of the marine cyanobacterium Lyngbya confervoides collected in Saipan, Commonwealth of the Northern Mariana Islands. Gross structure elucidation of this novel cyclic depsipeptide relied on extensive application of 2D NMR techniques. The absolute stereochemistry was deduced by chiral chromatography of the hydrolysis products and comparison with authentic and synthetic standards. Obyanamide (1) was cytotoxic against KB cells with an IC(50) of 0.58 microg/mL.     

Microspinosamide, a new HIV-inhibitory cyclic depsipeptide from the marine sponge Sidonops microspinosa

Microspinosamide (1), a new cyclic depsipeptide incorporating 13 amino acid residues, was isolated from extracts of an Indonesian collection of the marine sponge Sidonops microspinosa. Its structure was elucidated by extensive NMR and mass spectral analyses, and by chemical degradation and derivatization studies. The tridecapeptide 1 incorporates numerous uncommon amino acids, and it is the first naturally occurring peptide to contain a beta-hydroxy-p-bromophenylalanine residue. Microspinosamide (1) inhibited the cytopathic effect of HIV-1 infection in an XTT-based in vitro assay with an EC(50) value of approximately 0.2 microg/mL.