2 research outputs found
Krasilnikolides A and B and Detalosylkrasilnikolide A, Cytotoxic 20-Membered Macrolides from the Genus <i>Krasilnikovia</i>: Assignment of Anomeric Configuration by <i>J</i>‑Based Configuration Analysis
A chemical investigation of strain
RD003821, belonging to the underexplored
actinomycetes genus Krasilnikovia, led to the discovery
of three novel polyketides: two 20-membered glycomacrolides, krasilnikolides
A (1) and B (2), and an aglycone of 1, detalosylkrasilnikolide A (3). A major challenge
in the structure elucidation of 1 was to determine the
anomeric configuration of the α-l-6-deoxytalose (6dTal)
unit, which was achieved by J-based configuration
analysis (JBCA) that incorporated anomeric carbon- and proton-specific
two-bond 13C–1H spin–spin coupling
constants as diagnostic parameters. The updated criteria for the conformation/configuration
assignment facilitated discrimination of three out of four stereochemical
variants at the anomeric and the adjacent C2 positions, which expanded
the scope of the JBCA method to determination of the anomeric configuration
of aldohexopyranoses. Compounds 1 and 2 are
the first macrolides decorated by 6dTal. Compounds 1–3 exhibited cytotoxicity against P388 murine leukemia cells
with IC50 values of 14, 8.4, and 3.9 μM, respectively.
In addition, 1–3 were antibacterial
against the Gram-positive bacterium Kocuria rhizophila with MIC values of 25, 50, and 100 μg/mL. 1 was
inhibitory against Staphylococcus aureus with an
MIC of 50 μg/mL
Bacterial Production of the Tunicate-Derived Antitumor Cyclic Depsipeptide Didemnin B
Natural products obtained from marine invertebrates such
as sponges
and tunicates are attractive sources of drugs. However, a critical
obstacle in the development of these compounds is the problem of supply.
In most cases, neither chemical synthesis nor mariculture of invertebrates
is economically feasible. Due to structural similarities, many marine
natural products are suspected to be produced by associated microorganisms.
A favorable strategy for the production of such compounds is to use
culturable microorganisms. Here we report that didemnin B, a tunicate-derived
depsipeptide, has been isolated from a culturable bacterium, <i>Tistrella mobilis</i> YIT 12409