Erythrazoles A–B, Cytotoxic Benzothiazoles from a Marine-Derived <i>Erythrobacter</i> sp.

Chemical examination of an extract from an <i>Erythrobacter</i> sp. isolated from mangrove sediments yielded erythrazoles A (<b>1</b>) and B (<b>2</b>). The erythrazoles are of mixed biosynthetic origin containing a tetrasubstituted benzothiazole, an appended diterpene side chain, and a glycine unit. Erythrazole B is cytotoxic to a panel of non-small cell lung cancer (NSCLC) cell lines, with IC₅₀ values of 1.5, 2.5, and 6.8 μM against H1325, H2122, and HCC366, respectively

Thiasporines A–C, Thiazine and Thiazole Derivatives from a Marine-Derived <i>Actinomycetospora chlora</i>

Thiasporine A (<b>1</b>), the first natural product with a 5-hydroxy-4<i>H</i>-1,3-thiazin-4-one moiety, along with two new thiazole derivatives, thiasporines B and C (<b>2</b> and <b>3</b>), were isolated from the marine-derived <i>Actinomycetospora chlora</i> SNC-032. The structures of <b>1</b>–<b>3</b> were established on the basis of comprehensive spectroscopic analysis and chemical methods. Thiasporine A showed cytotoxicity against the non-small-cell lung cancer cell line H2122 with an IC₅₀ value of 5.4 μM

Spithioneines A and B, Two New Bohemamine Derivatives Possessing Ergothioneine Moiety from a Marine-Derived <i>Streptomyces spinoverrucosus</i>

Spithioneines A and B (<b>1</b> and <b>2</b>), two new bohemamine-type pyrrolizidine alkaloids possessing an unusual ergothioneine moiety, were isolated from a marine-derived <i>Streptomyces spinoverrucosus</i>. Their structures were elucidated by spectroscopic analysis, CD spectra, and chemical degradation and synthesis. Compounds <b>1</b> and <b>2</b> are rare natural products that incorporate the amino acid ergothioneine

Detailed Mechanistic Study of the Non-enzymatic Formation of the Discoipyrrole Family of Natural Products

Discoipyrroles A–D (DPA–DPD) are recently discovered natural products produced by the marine bacterium Bacillus hunanensis that exhibit anticancer properties in vitro. Initial biosynthetic studies demonstrated that DPA is formed in the liquid fermentation medium of B. hunanensis from three secreted metabolites through an unknown but protein-independent mechanism. The increased identification of natural products that depend on non-enzymatic steps creates a significant need to understand how these different reactions can occur. In this work, we utilized ¹⁵N-labeled starting materials and continuous high-sensitivity ¹H–¹⁵N HMBC NMR spectroscopy to resolve scarce reaction intermediates of the non-enzymatic discoipyrrole reaction as they formed in real time. This information guided supplemental experiments using ¹³C- and ¹⁸O-labeled materials to elucidate the details of DPA’s non-enzymatic biosynthesis, which features a highly concerted pyrrole formation and necessary O₂-mediated oxidation. We have illustrated a novel way of using isotopically enhanced two-dimensional NMR spectroscopy to interrogate reaction mechanisms as they occur. In addition, these findings add to our growing knowledge of how multicomponent non-enzymatic reactions can occur through inherently reactive bacterial metabolites

A Labeled Substrate Approach to Discovery of Biocatalytic Reactions: A Proof of Concept Transformation with <i>N-</i>Methylindole

Biocatalysis has become an important method in the pharmaceutical industry for the incorporation of new functionality in small molecules. Currently this method is limited in the types of reactions that can be carried out and no strategy exists to systematically screen for new biocatalyzed reactions. This study involves the development of a medium throughput screen to identify and optimize new reactions using a series of marine-derived bacterial cell lines, which were screened against several ¹³C labeled organic substrates. The reactions were analyzed using ¹³C NMR as the primary screening tool. We describe the discovery of a bacterial catalyzed indole oxidation reaction in which complete conversion of ¹³C labeled <i>N</i>-methyl indole to 3-hydroxyindole was observed. In addition, the sensitivity of this reaction to dO₂ levels can be exploited to oxidize to either 3-hydroxyindole or 2-oxoindole. This new platform sets up an important tool for the discovery of new organic transformations using an extensive library of marine bacteria

Daryamide Analogues from a Marine-Derived <i>Streptomyces</i> species

Three new cyclohexene amine derivatives, daryamides D–F (<b>1</b>–<b>3</b>), a new arylamine derivative, carpatamide D (<b>4</b>), and a new ornithine lactamization derivative, ornilactam A (<b>5</b>), were isolated from the marine-derived <i>Streptomyces</i> strain SNE-011. Their structures, including absolute configurations, were elucidated on the basis of spectroscopic analysis and chemical methods. The carpatamide skeleton could be considered as the biosynthetic precursor of the daryamides

1,3-Oxazin-6-one Derivatives and Bohemamine-Type Pyrrolizidine Alkaloids from a Marine-Derived <i>Streptomyces spinoverrucosus</i>

Two new 1,3-oxazin-6-one derivatives (<b>1</b> and <b>2</b>) and six new bohemamine-type pyrrolizidine alkaloids (<b>3</b>–<b>8</b>) were isolated from the marine-derived <i>Streptomyces spinoverrucosus</i> strain SNB-048. Their structures including the absolute configurations were fully elucidated on the basis of spectroscopic analysis, ECD spectra, quantum chemical calculations, and chemical methods. Compounds <b>1</b> and <b>2</b> possess a γ-lactam moiety and a 1,3-oxazin-6-one system

Ammosamide D, an Oxidatively Ring Opened Ammosamide Analog from a Marine-Derived <i>Streptomyces variabilis</i>

Ammosamide D (<b>1</b>), an oxidized analog of the ammosamide family, was isolated from a marine-derived <i>Streptomyces variabilis.</i> Pyrroloquinoline containing alkaloids are a growing class of natural products, with <b>1</b> being the first example of an oxidized analog resulting in a 5,6-dioxo-5,6-dihydroquinoline ring system. Attempts at chemical conversion of ammosamide B to ammosamide D revealed that a strong chemical oxidant is required. Ammosamide D has modest cytotoxicity to the MIA PaCa-2 pancreatic cancer cell line

Inducamides A–C, Chlorinated Alkaloids from an RNA Polymerase Mutant Strain of <i>Streptomyces</i> sp.

Inducamides A–C (<b>1</b>–<b>3</b>), three new chlorinated alkaloids featuring an amide skeleton generated by a tryptophan fragment and a 6-methylsalicylic acid unit, were isolated from a chemically induced mutant strain of <i>Streptomyces</i> sp. with the inducamides only being produced in the mutant strain. Their structures, including stereochemistry, were determined by spectroscopic analysis, Marfey’s method, and CD spectroscopy

Carpatamides A–C, Cytotoxic Arylamine Derivatives from a Marine-Derived <i>Streptomyces</i> sp.

Three new acylated arylamine derivatives (<b>1</b>–<b>3</b>), carpatamides A–C, were isolated from a marine-derived <i>Streptomyces</i> sp. based on activity screening against non-small-cell lung cancer (NSCLC). The structures of <b>1</b>–<b>3</b> were established on the basis of comprehensive spectroscopic analyses and chemical methods. Compounds <b>1</b> and <b>3</b> showed moderate cytotoxicity against NSCLC cell lines HCC366, A549, and HCC44 with IC₅₀ values ranging from 2.2 to 8.4 μM