Angucyclines: Biosynthesis, mode-of-action, new natural products, and synthesis.

@article{Kharel2012AngucyclinesBM,
  title={Angucyclines: Biosynthesis, mode-of-action, new natural products, and synthesis.},
  author={Madan K. Kharel and Pallab Pahari and Micah D. Shepherd and Nidhi Tibrewal and Stephen Eric Nybo and Khaled A. Shaaban and J{\"u}rgen Rohr},
  journal={Natural product reports},
  year={2012},
  volume={29 2},
  pages={
          264-325
        }
}
Key MethodCovering: 1997 to 2010. The angucycline group is the largest group of type II PKS-engineered natural products, rich in biological activities and chemical scaffolds. This stimulated synthetic creativity and biosynthetic inquisitiveness. The synthetic studies used five different strategies, involving Diels-Alder reactions, nucleophilic additions, electrophilic additions, transition-metal mediated cross-couplings and intramolecular cyclizations to generate the angucycline frames. Biosynthetic…Expand
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Careful consideration of the origin of the structure allowed us to outline a hypothesis on the biological function as well as prospective applications of such atypical angu cyclinones possessing an aromatic cleavage of the C-ring. Expand
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TLDR
A pair of enantiomeric nitrogen-containing angucyclinones, exhibited different strengths of antibacterial and cytotoxic activities, and were assigned by spectroscopic analysis, single-crystal X-ray diffractions, and equivalent circulating density (ECD) calculations. Expand
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TLDR
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References

SHOWING 1-10 OF 232 REFERENCES
Syntheses and biological evaluation of new glyco-modified angucyclin-antibiotics.
TLDR
The synthesis of novel aquayamycin-derived angucycline antibiotics 13a-d and 13a and 13b are some of the most potent xanthine oxidase inhibitors known and show cytotoxic activity with ED50-values in the range of 12.6-2.9x 10(-6) M. Expand
Oxidative rearrangement processes in the biosynthesis of gilvocarcin V.
TLDR
Various experiments are reported, which include incorporation studies with 18O-labeled precursors and the isolation and structure determination of novel intermediates of gilvocarcin biosynthesis accumulated by mutants, in which two genes encoding monooxygenases responsible for the C-C-bond cleavage of the gil Vocarcin pathway were deleted through targeted PCR. Expand
ANGUCYCLINES : TOTAL SYNTHESES, NEW STRUCTURES, AND BIOSYNTHETIC STUDIES OF AN EMERGING NEW CLASS OF ANTIBIOTICS
General and recent aspects of chemical syntheses on angucyclinones and selected related natural products are summarized here. In the first part of this review on angucyclines, the chemical reactionExpand
Sequential action of two flavoenzymes, PgaE and PgaM, in angucycline biosynthesis: chemoenzymatic synthesis of gaudimycin C.
TLDR
This in vitro study illustrates that the chemoenzymatic conversion of UWM6 into the metabolite, gaudimycin C, requires multiple closely coupled reactions to prevent intermediate degradation and suggests an alternative catalytic mechanism involving a quinone methide intermediate. Expand
Angucyclinone antibiotics: total syntheses of YM-181741, (+)-ochromycinone, (+)-rubiginone B2, (-)-tetrangomycin, and MM-47755.
TLDR
A concise and highly enantioselective route has been developed for the synthesis of angucyclinone-type natural products having the benz[a]anthraquinone skeleton based on a sequential intramolecular enyne metathesis, intermolecular Diels-Alder reaction (DAR), and aromatization. Expand
A biosynthetic pathway for BE-7585A, a 2-thiosugar-containing angucycline-type natural product.
TLDR
The results indicated an unusual manner of angular tetracyclic ring construction, perhaps via a Baeyer-Villiger type rearrangement, which set the stage for future biochemical studies of 2-thiosugar biosynthesis and BE-7585A assembly. Expand
Biosynthetic studies of aziridine formation in azicemicins.
TLDR
Support for the proposed biosynthetic pathway was obtained by showing that one of the adenylyltransferases specifically recognizes aspartic acid, providing strong evidence, in addition to the feeding experiments, that aspartate is the precursor of the aziridine moiety. Expand
Landomycins, new angucycline antibiotics from Streptomyces sp. I. Structural studies on landomycins A-D.
TLDR
The chemical structure of the new angucycline antibiotic landomycin A has been elucidated via chemical and spectroscopic methods, in particular by 2D NMR correlation spectroscopy, via long-range-couplings and heteronuclear multiple bond connectivity spectroscope sequences. Expand
Development of a convergent entry to the diazofluorene antitumor antibiotics: enantioselective synthesis of kinamycin F.
TLDR
Ortho-quinone methide intermediates, formed by reduction and loss of dinitrogen from 3, have been postulated to form in vivo, and the approach provides a straightforward synthetic pathway to such compounds. Expand
Engineering Anthracycline Biosynthesis toward Angucyclines
ABSTRACT The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silentExpand
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