Synthesis and properties of several isomers of the cardioactive steroid ouabain

Hong, Bor‐Cherng; Kim, Seongkon; Kim, Tae‐Seong; Corey, E. J.

doi:10.1016/j.tetlet.2006.02.089

Cited by 24 publications

(28 citation statements)

References 10 publications

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“…S3). However, it seems that inversion of OH11 α into an 11-epiouabain form would enable hydrogen bonding with Asn122, explaining its higher affinity (15). The above residues, with the exception of Glu117, have been identified by mutagenesis as crucial for ouabain binding (16,17).…”

Section: +mentioning

confidence: 99%

Crystal structure of the high-affinity Na ⁺ ,K ⁺ -ATPase–ouabain complex with Mg ²⁺ bound in the cation binding site

Laursen

Yatime

Nissen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

231

208

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Section: +mentioning

confidence: 99%

Crystal structure of the high-affinity Na ⁺ ,K ⁺ -ATPase–ouabain complex with Mg ²⁺ bound in the cation binding site

Laursen

Yatime

Nissen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

231

208

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“…This possibility was denied by the NMR spectra of bovine adrenal endogenous ouabain and on the basis of the observation that the 11 epimer of plant ouabain does not cochromatograph in HPLC with ouabain [25,49]. Similarly, the hypothalamic material was disproved as a sugar isomer of ouabain [41].…”

Section: Detectability Of Endogenous Ouabain In Biological Fluids or mentioning

confidence: 99%

Endogenous ouabain in cardiovascular function and disease

Manunta

Ferrandi²,

Bianchi

et al. 2009

Journal of Hypertension

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An endogenous ouabain has been isolated and conclusively identified from several mammalian tissues, including human plasma, by a number of independent laboratories. Substantial evidence from independent laboratories in several continents is consistent with an adrenal source for most if not all of the circulating endogenous ouabain. Accumulating evidence suggests that circulating levels of endogenous ouabain in humans are modulated by dietary salt and chronic volume status. Endogenous ouabain is linked significantly with vascular function in hypertension and likely impacts the pathogenesis of heart and renal failure. Moreover, the molecular mechanism of endogenous ouabain-linked hypertension involves the sodium pump/sodium-calcium exchange duet. The outstanding analytical issues include the elucidation of distal events in the biosynthetic pathway for endogenous ouabain and identification of molecular mechanisms that regulate its secretion and clearance.

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“…The use of cardiotonic steroids, however, is complicated by an extremely narrow therapeutic index, and patients are often treated with 60% of the toxic dose. Although structure-activity relationship studies have been conducted on cardenolides and related bufadienolides (14, 15), they have been limited to hydroxylated analogs and no studies have been done on other heterocyclic analogs. Thus, a de novo synthesis that would allow versatile topological diversification could lead to the development of further analogs potentially possessing a wider therapeutic window as safer alternatives (16).…”

mentioning

confidence: 99%

Strategic Redox Relay Enables A Scalable Synthesis of Ouabagenin, A Bioactive Cardenolide

Renata

Zhou

Baran

2013

Science

161

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Here we report a scalable route to the polyhydroxylated steroid ouabagenin with an unusual spin on the age-old practice of steroid semi-synthesis. The incorporation of both redox and stereochemical relays during the design of this synthesis resulted in efficient access to more than 500 mg of a key precursor towards ouabagenin–and ultimately ouabagenin itself–and the discovery of innovative methods for C–H and C–C activation and C–O bond hemolysis. Given the medicinal relevance of the cardenolides in the treatment of congestive heart failure, a variety of ouabagenin analogs could potentially be generated from the key intermediate as a means of addressing the narrow therapeutic index of these molecules.

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Synthesis and properties of several isomers of the cardioactive steroid ouabain

Cited by 24 publications

References 10 publications

Crystal structure of the high-affinity Na ⁺ ,K ⁺ -ATPase–ouabain complex with Mg ²⁺ bound in the cation binding site

Crystal structure of the high-affinity Na ⁺ ,K ⁺ -ATPase–ouabain complex with Mg ²⁺ bound in the cation binding site

Endogenous ouabain in cardiovascular function and disease

Strategic Redox Relay Enables A Scalable Synthesis of Ouabagenin, A Bioactive Cardenolide

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Synthesis and properties of several isomers of the cardioactive steroid ouabain

Cited by 24 publications

References 10 publications

Crystal structure of the high-affinity Na + ,K + -ATPase–ouabain complex with Mg 2+ bound in the cation binding site

Crystal structure of the high-affinity Na + ,K + -ATPase–ouabain complex with Mg 2+ bound in the cation binding site

Endogenous ouabain in cardiovascular function and disease

Strategic Redox Relay Enables A Scalable Synthesis of Ouabagenin, A Bioactive Cardenolide

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Product

Resources

About

Crystal structure of the high-affinity Na ⁺ ,K ⁺ -ATPase–ouabain complex with Mg ²⁺ bound in the cation binding site

Crystal structure of the high-affinity Na ⁺ ,K ⁺ -ATPase–ouabain complex with Mg ²⁺ bound in the cation binding site