Enantioselective Synthesis of a Highly Substituted Tetrahydrofluorene Derivative as a Potent and Selective Estrogen Receptor Beta Agonist

Autor:	Melissa E. Howard, Andrew W. Gibson, Alejandro Dieguez-Vazquez, Debra J. Wallace, Artis Klapars, Robert D. Wilson, Jeremy P. Scott, Peter R. Mullens, Andrew D. Gibb, Carl A. Baxter, Jaemoon Lee, Sarah E. Brewer, Stephen P. Keen, Ed Cleator, Nadine Bremeyer, Anthony Alorati, Kevin R. Campos, Matthew L. Maddess, Joseph J. Lynch, Jing Li
Rok vydání:	2014
Předmět:	Agonist Trifluoromethyl Stereochemistry Drug candidate medicine.drug_class Organic Chemistry Enantioselective synthesis chemistry.chemical_compound chemistry Yield (chemistry) medicine Physical and Theoretical Chemistry Estrogen receptor beta Derivative (chemistry)
Zdroj:	Organic Process Research & Development. 18:528-538
ISSN:	1520-586X 1083-6160
Popis:	The development and execution of a practical asymmetric synthesis of the estrogen receptor beta selective agonist (8R,10aS)-6-(trifluoromethyl)-8,9,10,11-tetrahydro-8,10a-methanocyclohepta[1,2]indeno[4,5-d][1,2,3]triazol-7(3H)-one is described. The optimized route features a key chiral auxiliary-mediated dialkylation approach to set the all-carbon quaternary center with exceptional stereocontrol. Overall, the chemistry has been used to prepare >30 kg of drug candidate in 21% overall yield through 13 longest linear steps and with >99% ee.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::fdefbcc65171430752e7a0100c3ac289 https://doi.org/10.1021/op5000489 Zobrazit plný text záznamu