A concise synthesis of (−)-indolmycin and (−)-5-methoxyindolmycin

Concise syntheses of (−)-indolmycin 1 and (−)-5-methoxyindolmycin 3 were developed based on a palladium-catalyzed reaction of (2S,3R)-2-acetoxy-3-methyl-5-trimethylsilyl-4-pentynoate 6 with an o-iodoaniline derivative 10 or 11, followed by reaction with guanidine hydrochloride in the presence of base. An optically active internal alkyne (2S 3R)-6 was obtained by lipase-assisted enantioselective acetylation of (±)-(2,3)-syn-2-hydroxy-3-methyl-5-trimethylsily-4-pentynoate 4.

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(2R,3S)-2-Hydroxy-3-methyl-5-trimethylsilyl-4-pentynoateC10H18O3SiEe = 94%[α]D25=-24.8 (c 1.13, CHCl3)Source of chirality: lipaseAbsolute configuration: (2R,3S)

(2S,3R)-2-Acetoxy-3-methyl-5-trimethylsilyl-4-pentynoateC12H20O4SiEe = 95%[α]D27=+12.05 (c 1.09, CHCl3)Source of chirality: lipaseAbsolute configuration: (2S,3R)