88594-72-3Relevant academic research and scientific papers
Application of biocatalysis towards asymmetric reduction and hydrolytic desymmetrisation in the synthesis of a β-3 receptor agonist
Badland, Matthew,Burns, Michael P.,Carroll, Robert J.,Howard, Roger M.,Laity, Daniel,Wymer, Nathan J.
, p. 2888 - 2894 (2011/12/05)
Chemoenzymatic syntheses of two key intermediates in the preparation of a potent β-3 receptor agonist 1 are described. A lipase-catalysed hydrolytic desymmetrisation is employed in a new synthesis of intermediate 7, which avoids the use of alkyl-tin reagents. A second biotransformation delivers chiral chlorohydrin 5 from its parent ketone in greater enantiomeric excess than the previously-described Noyori-reduction process. A brief discussion of the enantioselectivity of a set of single-point mutants of Sporobolomyces salmonicolor aldehyde reductase in this bioreduction is also presented.
The synthesis of two potent β-3 adrenergic receptor agonists
Bradley, Paul A.,Lecouturier, Yann C.,Noeureuil, Pierre,Patel, Bhairavi,Wheeler, Simon,Carroll, Robert J.,Moore, Robert,Snow, Jonathan
, p. 1326 - 1336 (2011/09/20)
This contribution describes the initial preparation of two potent β-3 receptor agonists 1 and 2. Subsequent scale up of these two compounds was required for further evaluation and proceeded via a common key amine intermediate 24. Synthesis of this key intermediate by way of a Ritter reaction was a vital step in the sequence. Enantioselective Noyori hydrogenation reactions gave access to the chiral epoxides necessary to make the target compounds. Chemistry was developed for the selective dehalogenation of the 2-chloropyridyl group in the presence of a sensitive isoxazole unit to provide access to 1.
