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Showing papers on "Wieland–Miescher ketone published in 1996"


Journal ArticleDOI
TL;DR: In this article, the tricyclic enone 2 was constructed via an intramolecular [4 + 2] cycloaddition, as schematized in Figure 1.
Abstract: It has been said that the active components in the Digitalis extracts have been “the most ingested drugs in medicine”.1 These substances, usually called cardenolides, differ from ordinary steroids in three major respects: the C/D ring system is cis rather than trans fused, there is a tertiary hydroxyl at C-14, and the substituent at C-17 (a butenolide) is in the thermodynamically less stable â orientation.2 As might be expected, many partial syntheses of cardenolides have been described starting with readily available steroids.3,4 We now report the total synthesis of natural (+)-digitoxigenin (1), the biologically active cardenolide which, as its trisaccharide derivative digitoxin, is one of the most frequently used of the active principles isolated from Digitalis species. We divided the synthesis, which we carried out both to racemic and to natural (+)-digitoxigenin, in three parts: synthesis of the tricyclic enone 2; elaboration of the fused 5-membered ring D to produce a tetracyclic system bearing both a 14-â-hydroxy substituent and a substituent at C-17 capable of further transformation; and, finally, elaboration of that substituent to the â-oriented butenolide system. We chose to approach the construction of the tricyclic enone 2 via an intramolecular [4 + 2] cycloaddition, as schematized in Figure 1. We initiated the synthesis from the monoketal (-)-3, prepared by applying to the readily available (S)-enantiomer of the Wieland Miescher ketone,5 the sequence previously described6 using its racemate. Ozonolysis of the trimethylsilyl enol ether of 3 gave, in a not unprecedented reaction,7 a mixture of R-hydroxy ketones which was reduced (NaBH4) to the corresponding glycols, followed by cleavage with periodate to the dialdehyde 4 (71% overall yield from 3). The two aldehyde groups in 4 now had to be differentially elaborated.

78 citations


Journal ArticleDOI
TL;DR: In this article, the enatioselective synthesis of (R)-3,4,8, 8, 8a-tetrahydro-8a-allyl-1,6-(2H, 7H)-naphthalenedione and the degradation of the angular allyl group to a hydroxymethyl group are reported.

16 citations


Journal ArticleDOI
TL;DR: In this paper, the structure of Wieland-Miescher ketone has been determined by X-ray crystallography after transformation of 5 into sultamamide 8a.2.
Abstract: Enolate of Wieland-Miescher ketone 1 has reacted with methyl acrylate to give methyl (1S*,2S*,4R*,6S*)-6-methyltricyclo[6.2.2.0 1,6]-dodecan-7, 12-dion-2-carboxylate 5 whose structure has been determined by X-ray crystallography after transformation of 5 into sultamamide 8a.

Journal ArticleDOI
TL;DR: In this article, the enatioselective synthesis of (R)-3,4,8, 8, 8a-tetrahydro-8a-allyl-1,6-(2H, 7H)-naphthalenedione and the degradation of the angular allyl group to a hydroxymethyl group are reported.
Abstract: The enatioselective synthesis of (R)-3,4,8,8a-tetrahydro-8a-allyl-1,6-(2H,7H)-naphthalenedione and the degradation of the angular allyl group to a hydroxymethyl group are reported.