- 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
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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.
- Morgan,Dodds,Zaks,Andrews,Klesse
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- Preparation method of posaconazole intermediate
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The invention relates to the technical field of medicine preparation, and especially relates to a preparation method of a posaconazole intermediate. The preparation method comprises the following steps: reacting a compound as shown in a formula II, serving as a raw material, with 1, 2, 4-triazole to obtain a compound as shown in a formula III, and then reacting with air or oxygen under the action of a catalyst 1 to obtain a compound as shown in a formula IV; reacting the compound as shown in the formula IV with dimethyl malonate to obtain a compound as shown in a formula V; reacting the compound shown in the formula V under the action of a reducing agent to obtain a compound shown in a formula VI; and finally, carrying out intramolecular etherification reaction on the compound shown in the formula VI, and carrying out sulfonylation reaction on the obtained product to obtain a target product I. The method has the advantages of cheap and easily available raw materials, mild reaction conditions, few reaction steps, high yield and high purity of the obtained product.
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Paragraph 0079-0093
(2021/11/21)
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