Forbedret kemisk fremgangsmåde til fremstilling af amidderivater af A 40926 antibiotikum

• Main Authors: PANZONE, GIANBATTISTA, GIANANTONIO, ANACLETO, MARAZZI, ALESSANDRA, MARIA, RESTELLI, ERMENEGILDO
• Format: Patent
• Language: Danish
• Published: 25.03.2002
• Edition: 6
• Subjects: CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES

Improved chemical process for preparing the compounds of formula (I), wherein: R1 represents (C9-C12)alkyl; M represents hydrogen, alpha-D-mannopyranosyl or 6-O-acetyl-alpha-D-mannopyranosyl and Y represents an amino group of formula -NR2-alk1-(NR3-alk2)p-(NR4-alk3)q-W. One aspect of the invention refers to the preparation of the intermediate compound of formula (III) (which corresponds to the above compound of formula (I)wherein R1 and M are as above defined and Y is hydroxy), by reacting a compound of formula (II) (which corresponds to the above compound of formula (I) wherein R1 and M are as above defined and Y is hydroxymethyl), with a (C1-C4)alkanol in the presence of a concentrated mineral acid, using the same alkanol as the reaction solvent and submitting the obtained ester compound to a reductive process by adding an alkali metal borohndride into the same reaction mixture. A further aspect of the invention refers to the amidation reaction for obtaining the compound of formula (I), which is carried out by reacting a compound of formula (III) with a suitable amine of formula (IV): NHR3-alk1-(NR4-alk2)p-(NR5-alk3)q-W, wherein R3, R4, R5, alk1, alk2, alk3, p, q and W are as defined in formula (I), in an inert organic solvent, in the presence of a condensing agent and setting the initial pH of the mixture (measured after diluting a sample of the reaction mixture with 9 volumes of water) at a value of from 6.5 to 9.0. By combining the above improved steps into a single process, it is possible to set up a particularly convenient process for preparing the compounds of formula (I). In addition, a purification method involving the use of polyamide resins and aqueous eluents is provided.