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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) [1a±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 SectionMethod 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.

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A series of 1,1'-spiro-substituted hexahydrofuroquinoline derivatives exhibiting potent cholesteryl ester transfer protein (CETP) inhibition at reduced lipophilicity was identified. A focused structure-activity relationship (SAR) exploration led to the potent and comparatively polar CETP inhibitor 26 showing robust high density lipoprotein-cholesterol (HDL-C) elevation and low density lipoprotein-cholesterol (LDL-C) reduction in transgenic hCETP/hApoB-100 mice. Compound 26 was also shown to positively differentiate from highly lipophilic CETP inhibitors in its complete elimination from fat tissue in hCETP transgenic mice as evident within 21 days after cessation of treatment. In addition, compound 26 showed no significant effects on aldosterone secretion from H295R cells, as well as no significant effects on blood pressure and electrocardiogram parameters in telemetrized cynomolgus monkeys.