169738-58-3Relevant academic research and scientific papers
Enzymatic desymmetrization of prochiral 2-substituted-1,3-propanediols: A practical chemoenzymatic synthesis of a key precursor of SCH51048, a broad- spectrum orally active antifungal agent
Morgan,Dodds,Zaks,Andrews,Klesse
, p. 7736 - 7743 (2007/10/03)
Two examples of a practical enzymatic desymmetrization of a 2- substituted-1,3-propanediol and their application to the synthesis of SCH51048, a broad-spectrum orally active antifungal, are described. In each case, enzymatic catalysis under both hydrolytic and transesterification conditions is described. In the first example the key intermediate, the R,S- monoester of triol 6, was obtained via Amano Lipase AK catalyzed hydrolysis of the dibutyrate 11b, or Novo SP435 catalyzed acetylation of triol 6. In the second example, desymmetrization of diol 13a using Novo SP435 or of dibutyrate 13c using Amano Lipase CE furnished the S-monoester (S)-14b,c, a key intermediate in a new efficient synthesis of SCH51048. Optimization of the Novo SP435 acetylation of diol 13a and the scaleup of the reaction is also described.
HIGHLY STEREOSELECTIVE ACCESS TO NOVEL 2,2,4-TRISUBSTITUTED TETRAHYDROFURANS BY HALOCYCLIZATION: PRACTICAL CHEMOENZYMATIC SYNTHESIS OF SCH 51048, A BROAD-SPECTRUM ORALLY ACTIVE ANTIFUNGAL AGENT
Saksena, Anil K.,Girijavallabhan, Viyyoor M.,Lovey, Raymond G.,Pike, Russell E.,Wang, Haiyan,et al.
, p. 1787 - 1790 (2007/10/02)
A convenient synthesis of (-)-(2R)-cis-tosylate 2 is reported via stereoselective 5-exo iodocyclization of the optically active 2,2-disubstituted olefin 9a.Enzymatic desymmetrization of the homoallylic diol 4 with Novo SP435 allowed optimal pro-(S) selectivity to provide the desired (-)-(S)-monoacetate 9a.Under the irreversible reaction conditions, the presence of a bulky aryl substituent on the 2,2-disubstituted olefin seems to determine stereochemical outcome of these halocyclizations.
