The title compound was isolated from the fermentation broth of Streptomyces sp. strain HC-21. A synthetic method for the preparation of the title compound was also reported. Asymmetric dihydroxylation of ethyl crotonate (I) using commercial AD-mix-beta produced diol (II). This was converted to the (2S,3R)-epoxide (III) by bromination with HBr in HOAc followed by cyclization of the resultant bromohydrin in the presence of DBU. Epoxide ring opening with the organomagnesium reagent generated from indole (IV) and methylmagnesium bromide furnished the chiral indolylbutanoate (V). Cyclization of the hydroxy ester (V) with guanidine hydrochloride (VI) in the presence of potassium tert-butoxide yielded the amino oxazolone (VII). Finally, displacement of the amino- by a methylamino group was achieved by treatment with aqueous methylamine.

The title compound was isolated from the fermentation broth of Streptomyces sp. strain HC-21. A synthetic method for the preparation of the title compound was also reported. Asymmetric dihydroxylation of ethyl crotonate (I) using commercial AD-mix-beta produced diol (II). This was converted to the (2S,3R)-epoxide (III) by bromination with HBr in HOAc followed by cyclization of the resultant bromohydrin in the presence of DBU. Epoxide ring opening with the organomagnesium reagent generated from indole (IV) and methylmagnesium bromide furnished the chiral indolylbutanoate (V). Cyclization of the hydroxy ester (V) with guanidine hydrochloride (VI) in the presence of potassium tert-butoxide yielded the amino oxazolone (VII). Finally, displacement of the amino- by a methylamino group was achieved by treatment with aqueous methylamine.

The condensation of the chiral epoxide (I) with indole (II) by means of methylmagnesium bromide in ethyl ether/dichloromethane gives the indolylbutyric ester (III), which is hydrolyzed with NaOH in ethanol/water and purified by crystallization to yield the corresponding butyric acid (IV). The esterification of (IV) with ethanol/HCl regenerates pure ester (III), which is cyclized with guanidine (V) by means of tBu-OK in tert-butanol to afford the oxazolone (VI). Finally the amino group of (VI) is methylated by means of methylamine in water to provide the target indolmycin.

The condensation of trans-epoxide (I) with indole (II) gives the racemic indolylbutyric acid (III), which is submitted to optical resolution with (+)-alpha-phenylethylamine to yield the (2S,3R)-enantiomer (2S,3R) (III). Finally, this compound is cyclized with N,N'.dimethylguanidine (IV) by means of Et-ONa in refluxing ethanol to afford the target indolmycin.

The reaction of indole-3-carbaldehyde (I) with benzyl chloroformate and NaH in THF gives the carbamate (II), which is condensed with the chiral oxazepinedione (III) by means of TiCl4 and pyridine in THF to yield a mixture of the cis (IV) and trans (V) adducts, which are easily separated by chromatography. The cis (IV) isomer can be thermally isomerized to the desired trans (V) isomer. The diastereoselective methylation of the double bond of (V) by means of MeMgBr in THF affords the methylated adduct (VI), which is hydrolyzed in acidic medium to afford the chiral indolylbutyric acid (VII). The reaction of (VII) with diazomethane provides the corresponding methyl ester (VIII), which is submitted to alpha hydroxylation by means of LDA, O2 and triethyl phosphite in HMPT/THF to give the chiral 2-hydroxy-3-(3-indolyl)butyric acid (IX). The protection of (IX) by means of dihydropyran (DHP) and Ts-OH yields the tetrahydropyranyl diprotected compound (X), which is hydrolyzed with LiOH in THF/water to afford the carboxylic acid (XI). The condensation of (XI) with N-methyl-thiourea (XII) by means of 2-chloro-3-ethylbenzoxazolium tetrafluoroborate (CEBF) and TEA in HMPT/dichloromethane provides a mixture of the S-acylisothiourea (XIII) and N-acylthiourea (XIV), which are easily separated. The S-acyl isomer (XIII) can be rearranged to the desired N-acyl isomer (XIV) by heating in refluxing dioxane. The N-acyl isomer (XIV) is deprotected by means of Ac-OH in THF/water to give the hydroxy derivative (XV), which is finally cyclized by means of CEBF and TEA in acetonitrile to afford the target indolmycin.