Supply chain: the polycyclic core of (-)-berkelic acid (1) was constructed in just one step from very simple starting materials. The total synthesis of 1 involves a seven-step linear sequence. Protection/deprotection steps were avoided and all but the last step were performed on a gram scale. This synthesis could solve the supply problem associated with the exhaustion of the natural source.
(–)‐Berkelic acid is an architecturally unique secondary metabolite isolated from an extremophilic Penicillium species. In this paper, we describe a very simple protocol to construct the central core of this natural product. Using this strategy, not only (–)‐berkelic acid, but also a small library of analogues has been accessed. The key point of our protocol is a remarkable silver‐catalysed cascade reaction that allows the assembly of the core of the natural product in a single step and from two simple starting materials, a 4‐pentynol derivative and an ortho‐alkynylsalicylaldehyde. The cytotoxicity of our synthetic (–)‐berkelic acid and some analogues against two cancer cell lines, OVCAR‐3 and SSCC38, was evaluated.
Nachschub gesichert: Der polycyclische Kern von (−)‐Berkelsäure (1) wurde in nur einem Schritt aus sehr einfachen Ausgangsverbindungen aufgebaut. Die Totalsynthese von 1 umfasst eine siebenstufige lineare Sequenz, die ohne Schützungs‐ und Entschützungsschritte auskommt. Alle Schritte, außer dem letzten, konnten im Gramm‐Maßstab durchgeführt werden.
Ortho-Alkynylbenzaldehydes have been widely used to generate isochromenylium derivatives through gold-catalyzed cycloisomerization. These isochromenylium derivatives have been exploited as formal diene derivatives for reactions with different dienophiles. Herein, we describe the behavior of ortho-alkynylsalicylaldehydes, a particular case of ortho-alkynylbenzaldehydes. The gold-catalyzed cycloisomerization of ortho-alkynylsalicylaldehydes delivers an unusual heterodiene derivative that reacts with electron-rich alkenes through a formal [4+2] cycloaddition. In this reaction, both the diene and dienophile are generated in situ through gold-catalyzed cycloisomerization of appropriate alkynamines or alkynols. This reaction was used to synthesize complex tetracyclic pyrano[2,3,4-de]chromenes from two very simple starting materials (an ortho-alkynylsalicylaldehyde and an alkynamine or alkynol) with complete atom economy and with selective formation of bonds, cycles, and stereocenters.
The reaction of simple β-ketoesters and propargylamines under gold(III) catalysis leads to the formation of the elusive 2,5-dihydropyridine system. This new reaction provides the synthesis of potentially bioactive compounds in moderate to high yields.
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