Cortisol and the glucocorticoid receptor (GR) signaling pathway has been linked to the development of diabetes and metabolic syndrome. In vivo, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to its active form, cortisol. Existing clinical data have supported 11β-HSD1 as a valid therapeutic target for type 2 diabetes. In our research program, (R)-1,1,1-trifluoro-2-(3-((R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)phenyl)propan-2-ol (HSD-016) was discovered to be a potent, selective, and efficacious 11β-HSD1 inhibitor and advanced as a clinical candidate. Herein, a reliable and scalable synthesis of HSD-016 is described. Key transformations include an asymmetric synthesis of a chiral tertiary alcohol via Sharpless dihydroxylation, epoxide formation, and subsequent mild reduction. This route ensured multikilogram quantities of HSD-016 necessary for clinical studies.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Several tetracyclic molecules were prepared by diene-transmissive Diels–Alder cycloadditions. Control over the stereochemical outcome of the cycloaddition was achieved and the structural features of the precursors affecting the stereochemistry is discussed. Useful information was gathered concerning the factors governing this stereocontrol, which will be indispensable for the future of this strategy.Key words: quassinoid, anticancer agent, diene-transmissive Diels–Alder cycloaddition, oxadiene, hetero Diels–Alder.

ChemInformVolume 34, Issue 26 Natural Products A Diene-Transmissive Approach to the Quassinoid Skeleton. Claude Spino, Claude Spino Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.Search for more papers by this authorBryan Hill, Bryan Hill Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.Search for more papers by this authorPascal Dube, Pascal Dube Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.Search for more papers by this authorStephane Gingras, Stephane Gingras Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.Search for more papers by this author Claude Spino, Claude Spino Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.Search for more papers by this authorBryan Hill, Bryan Hill Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.Search for more papers by this authorPascal Dube, Pascal Dube Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.Search for more papers by this authorStephane Gingras, Stephane Gingras Dep. Chim., Fac. Sci., Univ. Sherbrooke, Sherbrooke, Que. J1K 2R1, Can.Search for more papers by this author First published: 27 June 2003 https://doi.org/10.1002/chin.200326197AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Claude Spino, Bryan Hill, Pascal Dube, Stephane Gingras, A Diene-Transmissive Approach to the Quassinoid Skeleton., Can. J. Chem., 2003, 81, 81–108. 10.1139/v02-196 CASWeb of Science®Google Scholar Volume34, Issue26July 1, 2003 ReferencesRelatedInformation

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