Bradley S. Davidson

New dimensions in natural products research: cultured marine microorganisms

Abstract After almost 40 years of investigation, a period in which over 6000 new compounds have been discovered, marine natural products researchers have begun to view the marine environment from a different perspective. Marine microorganisms, including bacteria, fungi, and microalgae, most of which were previously ignored, have now come into focus as important new sources of biologically active compounds. Exciting recent results include the landmark structural characterization of maitotoxin, a dinoflagellate metabolite that is the most toxic and largest non-biopolymer ever studied, and the discovery of curacin A, a potential anticancer agent from a marine cyanobacterium. Although new compounds are being isolated from marine microorganisms, a great need exists for the development of microbiological methods that will allow the isolation and culture of microorganisms that are truly unique to the marine environment.

Renieramycin G, a new alkaloid from the sponge Xestospongia caycedoi

Abstract A new cytotoxic alkaloid, renieramycin G ( 8 ), was isolated, along with previously reported metabolites mimosamycin ( 1 ), renierol ( 2 ), and N -formyl-1,2-dihydrorenierone ( 3 ), from the Fijian sponge Xestospongia caycedoi . The structure of renieramycin G was deduced from spectral data.

New α-pyrone-containing metabolites from a marine-derived actinomycete

Abstract Four new α-pyrone-containing metabolites, wailupemycins A-C ( 1–3 ) and 3-epi-5-deoxyenterocin ( 4 ), were isolated together with known compounds enterocin ( 6 ) and 5-deoxyenterocin ( 5 ) from a Streptomyces sp. cultured from shallow water marine sediments. The structures of the new compounds were determined through the interpretation of spectral data. Compound 1 exhibited antimicrobial activity towards the Gram-negative bacterium Escherichia coli , while compound 4 inhibited the growth of Staphylococcus aureus .

Didemnolines A-D, new N9-substituted β-carbolines from the marine ascidian Didemnum sp.

Abstract Four new β-carboline-based metabolites, didemnolines A-D (1–4), were isolated along with eudistomin O (5), β-carboline (6), and 2-(2′,4′-dibromophenoxy)-3,5-dibromophenol (7) from an ascidian of the genus Didemnum, collected near the island of Rota, Northern Mariana Islands. These new β-carboline-based metabolites differ from most previously isolated compounds in that they are substituted at the N9 position of the β-carboline ring, rather than the C1 position.

Isolation and synthesis of caprolactins A and B, new caprolactams from a marine bacterium

Abstract Two new caprolactams have been isolated from an unidentified Gram-positive bacterium obtained from a deep-ocean sediment sample. Caprolactins A (1) and B (2), which were obtained as an inseparable mixture, are composed of cyclic-L-lysine linked to 7-methyloctanoic acid and 6-methyloctanoic acid, respectively. The structures were proposed using spectroscopic methods and confirmed by synthesis. Both caprolactins A and B are cytotoxic towards human epidermoid carcinoma (KB) cells and human colorectal adenocarcinoma (LoVo) cells and exhibit antiviral activity towards Herpes simplex type II virus.

Chirality in unsymmetrically substituted benzopentathiepins : the result of a high barrier to ring inversion

Abstract The 1H NMR spectrum of varacin (1), the first naturally-occurring compound determined to bear a 1,2,3,4,5-benzopentathiepin ring, shows unexpectedly complex signals for the side chain methylene protons. Evidence is presented which indicates that unsymmetrically substituted benzopentathiepins are asymmetric molecules as a result of a high energy barrier to inversion of the low energy chair conformations of the polysulfide ring. Derivatization of varacin with a chiral auxiliary provides diastereomeric products which can be separated by fractional recrystallization.

Synthesis of didemnolines A-D, N9-substituted β-carboline alkaloids from the marine ascidian Didemnum sp.

Didemnolines A-D (1–4) were synthesized and their structures were confirmed through comparisons of data for the synthetic material with those obtained for natural 1–4. The synthesis of didemnolines A (1) and C (3) involved the coupling of 1-[(benzyloxy)methyl]-4-chloromethyl-5-(thiomethyl)imidazole (6) with 7-bromo-β-carboline (5), while didemnolines B (2) and D (4) were formed through the analogous coupling of 6 with norharmon (7). Intermediate 6 was efficiently prepared from 1-[(benzyloxy)methyl]-2,4,5-tribromoimidazole using a sequential one-pot halogen-metal exchange reaction and 7-Br-β-carboline was synthesized using a new approach.

Plakortolide, a cytotoxic peroxylactone from a Plakortis sponge

A new cytotoxic cyclic peroxide-containing metabolite has been isolated from a Plakortis sponge. The molecular connectivity of plakortolide (4) was established using standard spectral methods, while the relative stereochemistry of the peroxylactone ring was deduced using a rotating frame nuclear Overhauser effect (ROESY) experiment.

Kailuins A–D, new cyclic acyldepsipeptides from cultures of a marine-derived bacterium

Abstract Four new cyclic acyldepsipeptides ( 1–4 ), assigned the trivial names kailuins A–D, have been isolated from liquid cultures of a Gram-negative bacterium (BH-107) obtained from driftwood collected at Kailua beach, Oahu. Structure elucidation employed 2-D NMR analyses, HRFABMS, and chemical derivazations. Kailuins A–D exhibited mild cytotoxicity when tested against certain human tumor cell lines.