The concanamycin group of macrolides, first isolated from a culture of Streptomyces diastatochromogenes Sp. S45 by Kinashi and co-workers and typified by concanamycin A (1, Figure 1) [1aΒ±d] and its aglycone, concanamycin F 2), [1e,f] exhibit potent inhibition of vacuolar (H ) ATPase activity. [2] The of a variety of sluggishly reactive and/or sparsely soluble hypervalent iodine reagents in water under neutral conditions. Further studies on the application of this system are now in progress.
Experimental Section
Method A (for primary alcohols): PhIO (0.44 mmol; Tokyo Chemical Industry Co., Ltd.) was added at room temperature to a stirred mixture of 1 (0.20 mmol) and KBr (0.04 mmol) in water (1.0 mL), and the mixture was stirred for 2 h. The resulting mixture was extracted with AcOEt, washed with brine, dried over Na 2 SO 4 , evaporated in vacuo, and the residue was purified by column chromatography (EtOAc/n-hexane) to give pure 2. Intermolecular esterification through nucleophilic attack on the initially formed aldehyde also proceeds under the conditions of Method B.
Method B (for secondary alcohols): Water (2.0 mmol) was added dropwise to a stirred mixture of 1 (0.2 mmol), PhIO (0.22 mmol), and KBr (0.2 mmol). The mixture was stirred or sonicated for several hours while checking the reaction progress by gas or thin-layer chromatography. After completion, n-hexane was added to the mixture, and then filtered. Evaporation of the solvent under vacuum afforded a crude product that was further purified by column chromatography (Et 2 O/n-hexane) to give pure 2.
Method C (for the oxidation with PSDIB): PSDIB (22 mmol), used without any pretreatment, was added at room temperature to a stirred suspension of 1 (20 mmol) and KBr (14 mmol) in water (40 mL), and the mixture was then sonicated for several hours. The resulting mixture was filtered and the residue containing 2 was washed with water to remove KBr, then extracted with n-hexane or MeOH, and the filtrate was evaporated to give 2. The product was purified by column chromatography, when necessary.