133407-38-2Relevant articles and documents
A scaleable synthesis of fiduxosin
Haight, Anthony R.,Bailey, Anne E.,Baker, William S.,Cain, Michael H.,Copp, Richard R.,Demattei, John A.,Ford, Kelley L.,Henry, Rodger F.,Hsu, Margaret C.,Keyes, Robert F.,King, Steven A.,McLaughlin, Maureen A.,Melcher, Laura M.,Nadler, William R.,Oliver, Patricia A.,Parekh, Shyamal I.,Patel, Hemant H.,Seif, Louis S.,Staeger, Mike A.,Wayne, Gregory S.,Wittenberger, Steven J.,Zhang, Weijiang
supporting information, p. 897 - 902 (2013/09/03)
Fiduxosin (1) has been under development at Abbott Laboratories for the treatment of benign prostatic hyperplasia. A convergent strategy required methodologies for preparation of an enantiomerically pure 3,4-cis-disubstituted pyrrolidine and a 2,3,5-trisubstituted thienopyrazine in a regiospecific manner. A [3+2] cycloaddition of an enantiopure azomethine ylide followed by a diastereoselective crystallization was employed to prepare the benzopyranopyrrolidine in high diastereomeric and enantiomeric purity. Conditions for reduction of an O-aryl lactone susceptible to epimerization were developed, and cyclization of the alcohol/phenol to the ether was accomplished in high yield. The thienopyrazine was prepared by condensation of methyl thioglycolate and a regiospecifically prepared 2-bromo-3-cyano-5-phenylpyrazine. Conditions for effective halogen substitutive deamination to prepare regiospecific trisubstituted pyrazines will be described.
Single and double diastereoselection in azomethine ylide cycloaddition reactions with unsaturated chiral bicyclic lactams
Fray,Meyers
, p. 3362 - 3374 (2007/10/03)
Double diastereoselectivity data were analyzed to provide insight into the structural features that influence π-facial selectivity in 1,3-dipolar cycloadditions of chiral and achiral azomethine ylides to chiral, unsaturated bicyclic lactams. Three major steric contributions to the differences in stability (ΔΔG(≠)) between competing cycloaddition transition states were identified. The first major set of steric interactions involve that between the dipoles and the substituents on the left hemisphere (R2) and concave faces of the bicyclic lactams. This effectively hindered both α- and β-approaches in the nonextended transition states. The second major steric interaction was provided by the nonbonded interactions (i) between the R1 angular substituent on the bicyclic lactam and the π-system of the dipole. This interaction was shown to be very significant, causing reversal in π-facial attack of chiral and achiral dipoles when the angular substituent is changed from phenyl or methyl to hydrogen. The high diastereoselectivity observed now opens a route to highly substituted chiral, nonracemic pyrrolidines.
A Synthesis of 1-Azabicycloheptane-3-carboxylic Acid Esters in Enantiomerically Pure Form
Cottrell, Ian F.,Hands, David,Kennedy, Derek J.,Paul, Kerensa J.,Wright, Stanley H. B.,Hoogsteen, Karst
, p. 1091 - 1097 (2007/10/02)
A novel synthesis of ethyl 1-azabicycloheptane-3-carboxylate via 1-benzylperhydropyranopyrrol-4-one and 1-benzyl-3-(2-bromoethyl)-4-ethoxycarbonylpyrrolidinium bromide is described.Modification of the method, by incorporation of a chiral substituted benzyl group on the nitrogen atom, has led to the first reported process for the preparation of these esters in enantiomerically pure form.The absolute configuration of the bicyclic esters was deduced by X-ray crystallography of an intermediate, 2-perhydropyranopyrrole-4-one.