62989-90-6Relevant academic research and scientific papers
Synthesis and activity of brefeldin A analogs as inducers of cancer cell differentiation and apoptosis
Zhu, Ji-Wen,Hori, Hitoshi,Nojiri, Hisao,Tsukuda, Takahiko,Taira, Zenei
, p. 139 - 144 (1997)
We designed and synthesized several brefeldin A (BFA) analogs. These compounds were evaluated for the ability to induce differentiation and apoptosis in human colonic carcinoma cell line HCT116. Diacetyl BFA (2a), 4-acetyl BFA (2b), 7-acetyl BFA (2c), and 10,11-epoxy BFA (3b) were active but tetrahydro BFA (3a) and other analogs could not induce the malignant cells to differentiate. The results suggested that the moiety from 1- to 4-position in BFA as well as its conformational rigidity is essential for its biological activity.
Site-selective oxidation, amination and epimerization reactions of complex polyols enabled by transfer hydrogenation
Hill, Christopher K.,Hartwig, John F.
, p. 1213 - 1221 (2017/11/28)
Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a large set of natural and synthetic compounds, often with potent biological activity. In synthetic chemistry, alcohols are important precursors to carbonyl groups, which then can be converted into a wide range of oxygen- or nitrogen-based functionality. Therefore, the selective conversion of a single hydroxyl group in natural products into a ketone would enable the selective introduction of unnatural functionality. However, the methods known to convert a simple alcohol, or even an alcohol in a molecule that contains multiple protected functional groups, are not suitable for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or reversible oxidation and reduction.
Oxidation of brefeldin A
Proksa,Uhrin,Adamcova,Fuska
, p. 582 - 584 (2007/10/02)
Oxidation of the macrolide antibiotic brefeldin A with pyridinium chlorochromate adsorbed on alumina afforded [6S, 10E, 11aS, 14E]-6-methyl-2,3,6,7,8,9,11a,12-octahydro-4 H-cyclopent[f]oxacyclotridecin-1,4,13-trione together with 13-oxobrefeldin. These compounds showed higher cytotoxic activity on P388 leukemia cells than brefeldin A, brefeldin A-1,13-diacetate, brefeldin A-13-acetate, tetrahydrobrefeldin or tetrahydrobrefeldin-1,13-dione. 13-Oxobrefeldin exceeded brefeldin A in antifungal activity on Candida albicans.
Biosynthesis of Macrolide Antibiotics. 6. Late Steps in Brefeldin A Biosynthesis
Yamamoto, Yoshikuni,Hori, Akira,Hutchinson, C. Richard
, p. 2471 - 2474 (2007/10/02)
Brefeldin A (1), a macrolide antibiotic produced by several fungi,contains a cyclopentanol rings as part of its 16-membered lactone.The role that the oxygen and double bond functionality at positions 2,3,4,7,10, and 11 play in the mechanism of 5-membered ring formation is examined by comparing the efficiency of incorporation of several isotopically labeled compounds into 1 which are putative intermediaties of the late part of the biosynthetic pathway.Brefeldin C (7-deoxybrefeldin A,3) and 7-oxobrefeldin A(2) were efficiently metabolized to 1,4-deoxibrefeldin C (8) was inneficiently metabolized to 1, but the 3,4-double bond isomers of 4-deoxybrefeldin C and 2,3,10,11-tetrahydrobrefeldin C were not metabolized to 1 by intact cells of Eupenicillium brefeldianum. 7-Oxobrefeldin A was found in the fungal cells,and a small amount of exogenously added brefeldin A was converted to 2 in vivo.These results support the intermediacy of 3 in the biosynthetic pathway of 1 and suggest that 1 and 2 can be interconverted by a biochemical redox process.The low conversion of 8 to1, however, suggests that it is not an intermediate of the main biosinthetic pathway to 1 but possibly only metabolized to 1 by a shunt pathway or by a nonspecific hydroxylase
