STUDIES ON LACTONES RELATED TO THE CARDIAC AGLYCONES. III. THE PROPERTIES OF β-SUBSTITUTED Δ<sup>α,β</sup>-BUTENOLIDES AND A SUGGESTED REVISION OF THE STRUCTURE OF THE SIDE CHAIN OF THE DIGITALIS-STROPHANTHUS AGLYCONES

Paist, Walter D.; Blout, E. R.; Uhle, Frederick C.; Elderfield, Robert C.

doi:10.1021/jo01202a012

Cited by 62 publications

(11 citation statements)

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“…Ex periments utilising Ziegler's N -bromosuccinimide method (110) Apart from various model �-substituted butenolides (113 to 118), the following compounds of t h e CXVI type have been prepared using these methods, but especially the first one.H �5-3 (�)-hydroxyetio cholenyl-butenolide (105,106,112), 3( a) -hydroxyetiocholanyl-buten olide (120), 3(�)-hydroxyalloetiocholanyHutenolidc (108,121,122), etiocholanyl-and 3 (�) -hydroxyetiocholanyl-butenolide( 14-des oxydigitoxigenin) (107), �5-3(�)-hydroxynorcholenyl -butenolide (112,123), norcholanyl-butenolide (124), 3(a)-hydroxyaIIoetiocho lanyl-and alloetiocholanyl-butenolide (122), 3(a),7(a), 12(�)-trihy droxynorcholanyl-butenolide (124,125), 3(a),12(�)-dihydroxyetio cholan y l-butenolide (109), N-3(�)�hydrox y etiocholen y lmethyl-and (log E = approx. 4.2) at approximately 215 to 220 m�l, in close agree ment with the values obtained with natural lactones of the digitalis and strophanthus types (131 ). They differ, however, from natural agly cones in lacking a hydroxyl group at C-14.…”

Section: Partial Synthesis Of Digitalis-like Aglyconessupporting

confidence: 87%

The Chemistry of the Steroids

Reichstein

Reich

1946

Annu. Rev. Biochem.

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Section: Partial Synthesis Of Digitalis-like Aglyconessupporting

confidence: 87%

The Chemistry of the Steroids

Reichstein

Reich

1946

Annu. Rev. Biochem.

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“…In the reaction between a glycoside molecule and the membrane, it seems likely that the steroid portion of the molecule confers the necessary solubility and geometrical properties, while the lactone ring provides the 'active centre'. Contrary to earlier views (see, for example, Jacobs, Hoffman & Gustus, 1926), the work of Paist, Blout, Uhle & Elderfield (1941), Ruzicka, Reichstein & Fiirst (1941) and Ruzicka, Plattner & Fiirst (1941) has now established that the double bond in the five-membered ring found in cardiac glycosides from sources other than squill is in the cx:f position, just as it is in the squill glycosides. This means that all the active glycosides possess unsaturated rings capable of showing resonance, the 'undisturbed' forms being…”

Section: Discussionmentioning

confidence: 70%

The action of cardiac glycosides on sodium and potassium movements in human red cells

Glynn¹

1957

The Journal of Physiology

651

312

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This paper describes the effects of a number of cardiac glycosides on the movements of sodium and potassium across the human red cell membrane. A preliminary account of some of the experiments reported here has already been published (Glynn, 1955). The aim of the work was, first, to decide whether the glycosides acted directly on the transport mechanism, and, secondly, to see if the effects of the glycosides could be made to yield any information about the molecular basis of cation transport.Many substances affect the movements of sodium and potassium but practically all of them act indirectly. Some, like the lysins, make the membrane leaky and so increase 'downhill' fluxes; others, like iodoacetate, inhibit energy metabolism and prevent active transport. In 1953 Schatzmann found that strophanthin, an active principle from Strophanthus gratus, prevented the uptake of potassium and elimination of sodium that normally occur when cold-stored red cells are incubated with glucose at 370C. Other cardiac glycosides have been found to give similar results (Joyce & Weatherall, 1955;Kahn & Acheson, 1955). Schatzmann, in his original paper, noted that concentrations of glycosides sufficient to affect ion movements had no effect on oxygen consumption or on lactic acid formation, and he concluded that the action of the drugs lay beyond the stage of energy production. It follows that the glycosides must act either by preventing energy released during glycolysis from reaching the ionic pump, or by interfering with the carrier mechanism itself. These two theories lead to different predictions, and experiments will be described which show that it is probably the second that is correct. The cardiac glycosides thus emerge as the only substances-apart of course from the metallic cations-which there is, at present, reason to believe act on the carrier system.It is of interest to know how much of the structure of the glycoside molecule is necessary for the action on the ion fluxes, and an attempt has been made

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“…2-Methylprop-1-ene-l-carboxylic acid lactone would be expected to show A. at about 216 m1z, since 2-cyclohexylprop-l-ene-l-carboxylic acid lactone shows . in this region (Paist, Blout, Uhle & Elderfield, 1941).…”

Section: Chch2ch2-ch2co-nh-ch-chmentioning

confidence: 86%