Kompakte Totalsynthese von Variecolortid A und B durch eine ungewöhnliche Hetero‐Diels‐Alder‐Reaktion

Abstract

Besondere Alkaloide aus Pilzen, die Variecolortide, scheinen eine Kombination aus bestimmten Anthrachinonen und Diketopiperazinen zu sein. Eine neue, kompakte Totalsynthese der Variecolortide A und B ergibt die natürlichen Racemate in beinahe schutzgruppenfreier und hoch konvergenter Weise. Sie verläuft über eine Hetero‐Diels‐Alder‐Reaktion eines 1,4‐Anthrachinons mit einem Didehydrodiketopiperazin zum Aufbau des spirocyclischen Kerns.

Evolution of a Synthetic Strategy for the Variecolortides

“…Indeed, under these conditions, we isolated compound 48 , which displays the crucial pyrano‐anthrone core of the variecolortides. Next, we tested the analogous reaction with the unprotected exo ‐methylene diketopiperazine 49 7 and also obtained the corresponding cycloadduct 50 in good yield. The synthesis of 47 , an analogue of exo ‐methylene diketopiperazine 20 is detailed in the Supporting Information.…”

“…Encouraged by these model studies, we proceeded to synthesize the three variecolortides, using isoechinulin B ( 45 ) or its desprenyl derivative neoechinulin B ( 51 )17 as dienophiles. The syntheses of these naturally occurring diketopiperazines using well‐established routes are shown in Scheme 7. We also obtained an X‐ray crystal structure of isoechinulin B ( 45 ), albeit in poor quality (see Supporting Information).…”

“…In a recent communication, our group published the syntheses of variecolortide A and B that hinged once again on a pericyclic reaction cascade 7. However, our eventual successful synthetic strategy was not our initial choice, but gradually evolved in the course of our investigations.…”

Chemistry of Polyhalogenated Nitrobutadienes, Part 11: ipso-Formylation of 2-Chlorothiophenes under Vilsmeier-Haack Conditions

“…The N-heteroaromatic haloenamine 3-chloro-1-methyl-1H-indole (8) [9], though, at 50 • C and with 1.1 eq. of phosphoryl chloride and an excess of DMF, afforded 3-chloro-1-methyl-1Hindole-2-carbaldehyde (9) as the main product with 30 % yield.…”

“…3-Chloro-1-methyl-1H-indole (8) was synthesized according to the literature for the synthesis of 3-chloro-1H-Brought to you by | University of Georgia Libraries Authenticated Download Date | 6/18/15 6:12 PM indole [9]. Under an atmosphere of nitrogen N-chlorosuccinimide (214 mg, 1.53 mmol) was added to a solution of 1methyl-1H-indole (7) (200 mg, 1.53 mmol) in anhydrous DMF (6 mL).…”