Fredericamycin A, an antitumor antibiotic of a novel skeletal type

Misra, Renuka; Pandey, Ramesh C.; Silverton, J. V.

doi:10.1021/ja00380a025

Cited by 114 publications

(39 citation statements)

References 2 publications

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“…Fredericamycin A (Fig. la, Misra, Pandey & Silverton, 1982) is an antitumour antibiotic which possesses a novel spiro[4.4]nonane system. This characteristic spatial imposition may have a role in determining its biological activity.…”

Section: 08 ~ 2]tridec-3-enementioning

confidence: 99%

Structure of 1,2'-spirobiindan-1',3'-dione, a key intermediate in the total synthesis of fredericamycin A

Acharya¹,

Puranik²,

Tavale³

et al. 1986

Acta Crystallogr C

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Section: 08 ~ 2]tridec-3-enementioning

confidence: 99%

Structure of 1,2'-spirobiindan-1',3'-dione, a key intermediate in the total synthesis of fredericamycin A

Acharya¹,

Puranik²,

Tavale³

et al. 1986

Acta Crystallogr C

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“…[1] However, linking a fluorescent probe to a small inhibitor can significantly alter Figure 1. Examples of naturally occurring cytotoxic compounds (1,2), and fluorescent probes (3)(4)(5), containing 2-pyridone-like motifs. its biological properties.…”

Section: Introductionmentioning

confidence: 99%

“…There exists many naturally occurring ring fused 2-pyridones with interesting biological activity, e.g. fredericamycin A, [2] 1, and camptotecin, [3] 2, which both are antitumor agents ( Figure 1). Carbostyrils, [4] 3, and naphthalimides, [5] 4, are well known fluorescent probes with versatile biological applications.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of a Multi Ring‐Fused 2‐Pyridone‐Based Fluorescent Scaffold

et al. 2010

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“…FDM A is a pentadecaketide-derived aromatic compound isolated from Streptomyces griseus ATCC 49344 in 1981 (10,14). It is notable for its remarkable antitumor potential and its unique carbaspirocyclic structure (15,16).…”

mentioning

confidence: 99%

Characterization of FdmV as an Amide Synthetase for Fredericamycin A Biosynthesis in Streptomyces griseus ATCC 43944

Chen

Wendt-Pienkowski

et al. 2010

Journal of Biological Chemistry

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Fredericamycin (FDM)AAmide bonds are common in natural products and represent fundamental linkages for numerous ribosomal and nonribosomal peptide-derived molecules; they are formed by the ribosome or by the condensation domain of nonribosomal peptide synthetases, respectively. Amide bonds can also be introduced into diverse natural products via different manifolds (Fig. 1). For instance, AdmF, a transglutaminase homolog, catalyzes amide bond formation in andrimid, highlighting a novel condensation strategy (1, 2). In the ansamycin-type antibiotics, the macrolactam ring in rifamycin is formed by an amide synthetase, RifF (3); whereas in some other macrolactams, like vicenistatin, the amide is proposed to result from thioesterase domain docking at the C terminus of the polyketide synthase (4). Alternative scenarios invoke amide bond formation as a tailoring step following construction of the core scaffold. For instance, in the aminocoumarin antibiotics, the amide bonds linking the 3-amino-4,7-dihydroxycoumarin moiety and related acyl moieties are formed by amide synthetases such as NovL (for novobiocin) and its homologs CloL, CouL, and SimL (5, 6). Novel novobiocin analogs can be envisioned by substituting NovL with the other three amide synthetases with significant substrate specificity discrepancies.As a major class of natural products, aromatic polyketides display an amazingly creative occupancy of chemical space translating often to their profound bioactivities. Despite the diversity of chemical structures displayed by aromatic polyketides, very few of them contain amide moieties. Several amide-containing aromatic polyketides are shown in Fig. 1. Among them, the amide moiety in oxytetracycline is proposed to originate from a specific malonamyl starter unit (7,8). In the case of lactonamycin, labeling studies suggest that the amino group originates from glycine or a glycine-derived starter unit (9). Fredericamycin (FDM) 2 A (10), pradimicin A (11), CBS40 (12), and lysolipin X (13) are all aromatic polyketides originating from polyketide chains of at least 24 carbons in length. Amide construction in these natural products has not yet received significant attention, and thus the mechanisms associated with these transformations remain obscure.FDM A is a pentadecaketide-derived aromatic compound isolated from Streptomyces griseus ATCC 49344 in 1981 (10, 14). It is notable for its remarkable antitumor potential and its unique carbaspirocyclic structure (15, 16). We previously cloned and sequenced the fdm gene cluster, setting the stage to study the biosynthetic pathway responsible for FDM A production (17). Reexamination of S. griseus wild-type fermentation recently resulted in the isolation of three FDM analogs FDM B, FDM C, and FDM E (18,19) (Fig. 2). FDM B and FDM E both contain the lactam ring F, and FDM C has a carboxylic acid group comparably situated. These facts support the proposal that the amide nitrogen of FDM A is incorporated following installation of the polycyclic ring system. The * This work was su...

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Fredericamycin A, an antitumor antibiotic of a novel skeletal type

Cited by 114 publications

References 2 publications

Structure of 1,2'-spirobiindan-1',3'-dione, a key intermediate in the total synthesis of fredericamycin A

Structure of 1,2'-spirobiindan-1',3'-dione, a key intermediate in the total synthesis of fredericamycin A

Synthesis and Characterization of a Multi Ring‐Fused 2‐Pyridone‐Based Fluorescent Scaffold

Characterization of FdmV as an Amide Synthetase for Fredericamycin A Biosynthesis in Streptomyces griseus ATCC 43944

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