Total synthesis of rac-9,11-dehydrodigitoxigenin 3-tetrahydropyranyl ether

Daniewski, A. R.; Kabat, Marek; Masnyk, Marek; Wicha, J.; Wojciechowska, Wanda; Duddeck, H.

doi:10.1021/jo00255a036

Cited by 23 publications

(8 citation statements)

References 2 publications

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“…Interestingly, as noted in an earlier section, Daniewski and coworkers found that introduction of unsaturation (D 9, 11 ) in a similar substrate (33) yields a stereoisomeric (C13b-H/C14b-OH) aldol product (34). [31] These two divergent outcomes have been attributed to differing cyclopentadione conformations and distinct spatial orientations of the ketone carbonyl toward the enolate, synclinal in the case of Deslongchamps et al (Scheme 10, TS-II) [49] and antiperiplanar for the Daniewski example (see Scheme 2, TS-I). These results underscore the subtle structural features responsible for observed stereocontrol in such highly complex annulation processes.…”

Section: Wwwchemeurjorgmentioning

confidence: 68%

“…Daniewskis total synthesis of (+ /À)-9,ll-dehydrodigitoxigenin: Daniewski and co-workers disclosed the first total synthesis of the cardenolide steroidal framework [31] starting from the Wieland-Miescher ketone (Scheme 2), which is readily available in racemic form or by using a well-known asymmetric synthesis starting from proline (Hajos-Parrish reaction). [32] The key transformation of the Daniewski route is a stereocontrolled aldol condensation that forms the steroid C-ring and defines three new chiral centers.…”

Section: Total Synthesis Of Cardenolidesmentioning

confidence: 99%

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Chemical Synthesis of the Cardiotonic Steroid Glycosides and Related Natural Products

Heasley

2012

Chemistry A European J

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The active components from the extracts of Digitalis, cardiotonic steroid glycosides, have been ingested by humans for more than 200 years as a medicinal therapy for heart failure and abnormal heart rhythms. The positive inotropic activity of the cardiotonic steroids that mediates clinically useful physiological effects in patients has been attributed largely to a high affinity inhibitory interaction with the extracellular surface of the membrane-bound sodium pump (Na(+)/K(+)-ATPase). However, previously unrecognized intracellular signaling pathways continue to be uncovered. This Review examines both partial and de novo synthetic approaches to the medicinally important and structurally captivating cardenolide and bufadienolide steroid families, with an emphasis on the stereocontrolled construction of the pharmacophoric aglycone (genin) framework.

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Section: Wwwchemeurjorgmentioning

confidence: 68%

Section: Total Synthesis Of Cardenolidesmentioning

confidence: 99%

Chemical Synthesis of the Cardiotonic Steroid Glycosides and Related Natural Products

Heasley

2012

Chemistry A European J

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“…Despite the long history of research in this area, the interest in cardenolides continues. Recently reported work on cardenolides includes the total synthesis of digitoxigenin1,5 and ouabain,6 biosynthesis7 and the search for new, less toxic digitalis‐like compounds with better pharmacological properties for therapeutic use 8. It has recently been reported that cardenolides have a growth inhibitory effect on cancer cell lines9 and show antiproliferative10 and cytotoxic11 activity.…”

Section: Introductionmentioning

confidence: 99%

Cyclobutanone Approach to the Synthesis of Cardenolides

2005

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17β‐(3‐Oxocyclobutyl)androstane, prepared by the thermal [2 + 2] cycloaddition of dichloroketene to 3β‐acetoxypregna‐5,20‐diene, is the key intermediate in the new, efficient synthesis of steroids bearing the 17β‐butenolide fragment that characterizes cardenolides. The six‐step synthesis of 3β‐tert‐butyldimethylsilyloxy‐14α‐carda‐5,20(22)‐dienolide was achieved with a total yield of 32%. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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“…Quite recently, Daniewsi and Wicha reported that 14β-hydroxy-17β-cyanoandrostane derivatives were good starting materials for the synthesis of digitoxigenin and its 9(11)-dehydro derivative. The introduction of the 17β-cyano group was easily and selectively accomplished from a 14β-hydroxy-17α-iodo derivative via an S N 2-type free-radical reaction with tert -butyl isocyanide without the protection of the 14β-hydroxy function.…”

mentioning

confidence: 99%