A New Antitumor Antibiotic, Kidamycin

Kanda, Nobuo; Kono, Morihiro; Asano, Kazuo

doi:10.7164/antibiotics.25.553

Cited by 21 publications

(13 citation statements)

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“…32 Given its planar tetracyclic core structure, it is not surprising that kidamycin, like other pluramycin antibiotics, binds to DNA leading to single strand cleavage. 33 …”

Section: Furans As Building Blocks For C-aryl Glycoside Synthesismentioning

confidence: 99%

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Martin

2017

J. Org. Chem.

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Diverse structural types of natural products and their mimics have served as targets of opportunity in our laboratory to inspire the discovery and development of new methods and strategies to assemble polyfunctional and polycyclic molecular architectures. Furthermore, our efforts toward identifying novel compounds having useful biological properties led to the creation of new targets, many of which posed synthetic challenges that required the invention of new methodology. In this Perspective, selected examples of how we have exploited a diverse range of natural products and their mimics to create, explore, and solve a variety of problems in chemistry and biology will be discussed. The journey was not without its twists and turns, but the unexpected often led to new revelations and insights. Indeed, in our recent excursion into applications of synthetic organic chemistry to neuroscience, avoiding the more-traveled paths was richly rewarding.

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“…32 Given its planar tetracyclic core structure, it is not surprising that kidamycin, like other pluramycin antibiotics, binds to DNA leading to single strand cleavage. 33 …”

Section: Furans As Building Blocks For C-aryl Glycoside Synthesismentioning

confidence: 99%

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Martin

2017

J. Org. Chem.

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“…It is active against Gram positive bacteria, and it exhibits anticancer activity against Ehrlich ascites carcinoma, leukemia L1210, sarcoma-180, NF-sarcoma and Yoshida sarcoma. 7 Hurley and coworkers, who have extensively studied the mode of action of the pluramycin natural products, 8 found that the pluramycins intercalate into the DNA helix by positioning the carbohydrate residues in both the major and minor grooves of the helix. The complex is stabilized by hydrogen-bonds between the protonated dimethylamino groups of the sugar moieties and the DNA strand.…”

Section: Introductionmentioning

confidence: 99%

“…The complex is stabilized by hydrogen-bonds between the protonated dimethylamino groups of the sugar moieties and the DNA strand. The side-chain epoxide of pluramycin A then alkylates N7 of a guanine residue leading to formation of a cationic lesion in the DNA that can lead to single strand cleavage in the presence of base.Kidamycin has been shown to be cardiotoxic and possesses an LD 50 of 18 mg/kg in mice; 7a however, it also significantly prolongs the life of mice bearing Ehrlich ascites tumors at single doses (i.p.) as low as one-sixteenth of the LD 50 .…”

Section: Introductionmentioning

confidence: 99%

Studies toward the syntheses of pluramycin natural products. The first total synthesis of isokidamycin

et al. 2011

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We report the first total synthesis of the complex C-aryl glycoside isokidamycin, the epimer of the naturally-occurring pluramycin antibiotic kidamycin. The synthesis features a highly efficientDiels-Alder reaction between a substituted naphthyne and a glycosylatedfuran to form the anthracene core bearing a pendant angolosamine C-glycoside. The regiochemical outcome of the Diels-Alder reaction was controlled by employing a disposable silicon-tether to link the reactive napthyne and the glycosyl furan, rendering the cycloaddition intramolecular. The benzopyranone moietyof the aromatic nucleus was appended by cyclization of a functionalized vinylogous amide onto an advanced anthrol intermediate. The vancosamine amino glycoside was introduced by an O→C-glycoside rearrangement that produced the β-anomer. Subsequent refunctionalizations then led to isokidamycin.

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“…1 Many of these biologically relevant molecules possess substitution at both positions ortho to the ketone moiety. For example, kidamycin ( 1 ), a potent anti-cancer antibiotic, contains a benzopyranone motif that possesses this substitution pattern, 2 as do simpler natural products, including luteolin ( 2 ) and aureusidin ( 3 ) (Figure 1). 3 An efficient approach toward the total synthesis of any of these natural products will necessarily mandate installing the ortho -disubstituted aryl ketone functional group with minimal synthetic manipulations.…”

Section: Introductionmentioning

confidence: 99%

Facile access to sterically hindered aryl ketones via carbonylative cross-coupling: application to the total synthesis of luteolin

2011

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A general and mild protocol for achieving the carbonylative cross-coupling of sterically-hindered, ortho-disubstituted aryl ketones is reported. The commercially available PEPPSI-IPr catalyst is shown to efficiently promote the carbonylative cross-coupling of hindered ortho-disubstituted aryl iodides to give diaryl ketones; traditional phosphine catalysts are less effective. Carbonylative Suzuki-Miyaura cross-couplings provide a diverse array of biaryl ketones in good to excellent yields. The same catalyst is also shown to catalyze a carbonylative Negishi cross-coupling reaction, utilizing a variety of alkynyl zinc reagents to give the corresponding alkynyl aryl ketones. Application of this new methodology to the synthesis of the natural product luteolin is reported.

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A New Antitumor Antibiotic, Kidamycin

Cited by 21 publications

References 0 publications

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Studies toward the syntheses of pluramycin natural products. The first total synthesis of isokidamycin

Facile access to sterically hindered aryl ketones via carbonylative cross-coupling: application to the total synthesis of luteolin

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