Total Synthesis and Structural Confirmation of the Antimalarial Naphthopyrone Lasionectrin

Abstract

The total synthesis of lasionectrin, a naphthopyrone metabolite of an Acremonium-like fungus collected in Equatorial Guinea, is reported. Divergent access to four stereoisomers confirmed the natural product to be the enantiomer of the originally proposed structure. Highlights of the synthesis include ring opening of a chiral oxetane using a thiol, a highly E-selective Julia-Kocienski olefination, and a modified Sharpless/Upjohn dihydroxylation. Palladium-catalyzed carbonylative lactonization was used to assemble the fused naphthopyrone ring system.

Enantioselective Total Synthesis of (+)-Monocerin, a Dihydroisocoumarin Derivative with Potent Antimalarial Properties

“…To complete the synthesis of monocerin, selective deprotection of methyl ether was carried out by exposure to BCl 3 in CH 2 Cl 2 at −10 °C for 2 h to provide synthetic (+)-monocerin 1 in 41% yield (88% brsm). The 1 H NMR and 13 C NMR spectra of synthetic (+)-monocerin {[α] D 23 + 57.8 (c 0.29, CHCl 3 )} are in complete agreement with spectra reported for the natural (+)-monocerin {[α] D 24 + 53 (c 0.85, CHCl 3 )}. 6 We have also synthesized (+)-acetoxymonocerin 2 by treatment of 1 with acetic anhydride and pyridine in the presence of a catalytic amount of DMAP at 0 to 23 °C for 5 h to furnish acetate derivative 2 in 96% yield.…”

“…Since then, monocerin and its derivatives have attracted much synthetic interest due to their broad medicinal potential. A number of total syntheses of monocerin have been reported. − Recently, an enantioselective total synthesis of lasionectrin has also been reported . Herein, we report a short and practical synthesis of monocerin and its acetate derivative in optically active form.…”

“…18−23 Recently, an enantioselective total synthesis of lasionectrin has also been reported. 24 Herein, we report a short and practical synthesis of monocerin and its acetate derivative in optically active form. The synthesis features Sharpless asymmetric dihydroxylation, Lewis acid-catalyzed, oxocarbenium ion-mediated stereoselective allylation, formulation reaction, and CrO 3 -mediated oxidation of the benzopyran to a dihydroisocoumarin derivative.…”

Minor Pyranonaphthoquinones from the Apothecia of the Lichen Ophioparma ventosa

“…On the basis of these aforementioned data, the 2D structure of compound 1 was established as depicted in Figure 1. This dihydrofurano-fused α-pyrone system has been reported for a limited number of naphthopyranones, 15 for example, lasionectrin 8,16 and lichenicolins A and B. 9 Its fusion with a naphthazarin core is described here for the first time.…”

Palladium‐catalyzed Synthesis of Fused Carbo‐ and Heterocycles

“…Furkert and Brimble group derived a method of total synthesis of antimalarial naphthopyrone lasionectrin (Scheme 18). [28] Julia‐Kocienski's coupling of naphthaldehyde 54 in presence of KHMDS, and lithium chloride under tetrahydrofuran solvent at −20 °C for 2 h gave a highly selective desired product of E isomer in excellent yield. TBS‐protected product was obtained in 94% yield with E selectivity under the same reaction condition as well as acetate‐protected product was derived in 75% yield with E selectivity.…”