25 research outputs found
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 IC<sub>50</sub> 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 IC<sub>50</sub> 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 <sup>15</sup>N-labeled starting materials and continuous high-sensitivity <sup>1</sup>H–<sup>15</sup>N 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 <sup>13</sup>C- and <sup>18</sup>O-labeled materials
to elucidate the details of DPA’s non-enzymatic biosynthesis,
which features a highly concerted pyrrole formation and necessary
O<sub>2</sub>-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 <sup>13</sup>C labeled organic substrates.
The reactions were analyzed using <sup>13</sup>C NMR as the primary
screening tool. We describe the discovery of a bacterial catalyzed
indole oxidation reaction in which complete conversion of <sup>13</sup>C labeled <i>N</i>-methyl indole to 3-hydroxyindole was
observed. In addition, the sensitivity of this reaction to dO<sub>2</sub> 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 IC<sub>50</sub> values ranging from 2.2 to 8.4
μM