Cardenolide Analogs. 1. A 17β-Unsaturated Aldehyde

Dwight S. Fullerton; Marvin C. Pankaskie; Khalil Ahmed; Arthur H.L. From

doi:10.1021/jm00233a015

Cardenolide Analogs. 1. A 17β-Unsaturated Aldehyde

Dwight S. Fullerton, Marvin C. Pankaskie, Khalil Ahmed, Arthur H.L. From

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Abstract

A 17β-unsaturated aldehyde analogue [3β,14β-dihydroxy-5β-pregn-17β-trans-20-en-22-al (7)] of the cardenolides was synthesized and studied. In earlier studies by Rappoport, unsaturated aldehydes were found to be highly active electrophiles, more active, for example, than unsaturated nitriles or methyl esters. The synthesis followed in part a scheme previously reported by Thomas for the syntheses of the 17β-unsaturated nitrile 9 and the 17β-unsaturated methyl and ethyl esters 8 and 10. Both 9 and 8 are more Na⁺,K⁺-ATPase inhibiting and slightly less inotropic than digitoxigenin (lb). However, the unsaturated aldehyde 7 was less Na⁺,K⁺-ATPase inhibiting (I₅₀ = 9.9 ± 0.7 × 10^-7 M) and less inotropic (100% increase in contractile force at 8.5 ± 1.0 × ×10^-6 M) than 1b (I₅₀ = 4.6 ± 1.6 × 10^-7 M; 100% increase at 3.0 ± 1.0 × 10^-7 M).

Original language	English (US)
Pages (from-to)	1330-1333
Number of pages	4
Journal	Journal of medicinal chemistry
Volume	19
Issue number	11
DOIs	https://doi.org/10.1021/jm00233a015
State	Published - Nov 1 1976

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title = "Cardenolide Analogs. 1. A 17β-Unsaturated Aldehyde",

abstract = "A 17β-unsaturated aldehyde analogue [3β,14β-dihydroxy-5β-pregn-17β-trans-20-en-22-al (7)] of the cardenolides was synthesized and studied. In earlier studies by Rappoport, unsaturated aldehydes were found to be highly active electrophiles, more active, for example, than unsaturated nitriles or methyl esters. The synthesis followed in part a scheme previously reported by Thomas for the syntheses of the 17β-unsaturated nitrile 9 and the 17β-unsaturated methyl and ethyl esters 8 and 10. Both 9 and 8 are more Na+,K+-ATPase inhibiting and slightly less inotropic than digitoxigenin (lb). However, the unsaturated aldehyde 7 was less Na+,K+-ATPase inhibiting (I50 = 9.9 ± 0.7 × 10-7 M) and less inotropic (100% increase in contractile force at 8.5 ± 1.0 × ×10-6 M) than 1b (I50 = 4.6 ± 1.6 × 10-7 M; 100% increase at 3.0 ± 1.0 × 10-7 M).",

author = "Fullerton, {Dwight S.} and Pankaskie, {Marvin C.} and Khalil Ahmed and From, {Arthur H.L.}",

year = "1976",

month = nov,

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doi = "10.1021/jm00233a015",

language = "English (US)",

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T1 - Cardenolide Analogs. 1. A 17β-Unsaturated Aldehyde

AU - Fullerton, Dwight S.

AU - Pankaskie, Marvin C.

AU - Ahmed, Khalil

AU - From, Arthur H.L.

PY - 1976/11/1

Y1 - 1976/11/1

N2 - A 17β-unsaturated aldehyde analogue [3β,14β-dihydroxy-5β-pregn-17β-trans-20-en-22-al (7)] of the cardenolides was synthesized and studied. In earlier studies by Rappoport, unsaturated aldehydes were found to be highly active electrophiles, more active, for example, than unsaturated nitriles or methyl esters. The synthesis followed in part a scheme previously reported by Thomas for the syntheses of the 17β-unsaturated nitrile 9 and the 17β-unsaturated methyl and ethyl esters 8 and 10. Both 9 and 8 are more Na+,K+-ATPase inhibiting and slightly less inotropic than digitoxigenin (lb). However, the unsaturated aldehyde 7 was less Na+,K+-ATPase inhibiting (I50 = 9.9 ± 0.7 × 10-7 M) and less inotropic (100% increase in contractile force at 8.5 ± 1.0 × ×10-6 M) than 1b (I50 = 4.6 ± 1.6 × 10-7 M; 100% increase at 3.0 ± 1.0 × 10-7 M).

AB - A 17β-unsaturated aldehyde analogue [3β,14β-dihydroxy-5β-pregn-17β-trans-20-en-22-al (7)] of the cardenolides was synthesized and studied. In earlier studies by Rappoport, unsaturated aldehydes were found to be highly active electrophiles, more active, for example, than unsaturated nitriles or methyl esters. The synthesis followed in part a scheme previously reported by Thomas for the syntheses of the 17β-unsaturated nitrile 9 and the 17β-unsaturated methyl and ethyl esters 8 and 10. Both 9 and 8 are more Na+,K+-ATPase inhibiting and slightly less inotropic than digitoxigenin (lb). However, the unsaturated aldehyde 7 was less Na+,K+-ATPase inhibiting (I50 = 9.9 ± 0.7 × 10-7 M) and less inotropic (100% increase in contractile force at 8.5 ± 1.0 × ×10-6 M) than 1b (I50 = 4.6 ± 1.6 × 10-7 M; 100% increase at 3.0 ± 1.0 × 10-7 M).

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IS - 11

ER -

Cardenolide Analogs. 1. A 17β-Unsaturated Aldehyde

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