Patent ID: 6528628
Filing Date: 2003-03-04
Classification: A61P,C07H

Abstract:
A process for preparing 6-O-alkyl erythromycin A 9-oxime and 6-O-alkyl erythromycin A represented by the following formula (II) which comprises the steps (a) to (e):(a) reacting erythromycin A 9-oxime represented by the following formula (III) with a bifunctional linker represented by the following formula (IV) to give an erythromycin A 9-oxime compound represented by the following formula (V); (b) silylating the erythromycin A 9-oxime compound of formula (V) obtained in the step (a) to give an erythromycin A 9-oxime compound represented by the following formula (VI); (c) alkylating the compound of formula (VI) obtained in the step (b) to give an erythromycin A 9-oxime compound represented by the following formula (VII); (d) desilylating the erythromycin A 9-oxime compound of formula (VII) obtained in step (c) to give an erythromycin A 9-oxime compound represented by the following formula (VIII); and (e) removing the oxime protecting group of the compound of formula (VIII) obtained in the step (d) or consecutively carrying out removal of the oxime protecting group and deoximation reaction: â€ƒwherein, R represents a C1-3 alkyl group; R1 and R2 each independently represents a silyl group represented by â€”SiR4R5R6 in which R4, R5, and R6 each independently represents a C1-6 alkyl group, a C1-3 alkyl group substituted with a phenyl group, a phenyl group, a C5-7 cycloalkyl group, or a C2-5 alkenyl group; or R2 represents hydrogen; R3 represents hydrogen, a 1-alkenyl group, or an aryl group; Q represents a cis- or trans-alkenylene group represented by â€”(CH&boxH;CH)mâ€”, a &agr;,&ohgr;-dienylene group represented by â€”[CH&boxH;CHâ€”(CH2)mâ€”CH&boxH;CH]â€”, a phenyl group consisting of ortho-, meta- or para-, an arylene group or an alkylene group represented by â€”(CH2)nâ€” when R3 represents a 1-alkenyl group or an aryl group, m is an integer of 1 to 3, and n is an integer of 1 to 10, wherein one or more carbons in the above alkylene group, alkenylene group, dienylene group or arylene group may be substituted with an alkyl substituent; X represents O or Nâ€”OH; and Y represents chloride, bromide, iodide, mesylate, tosylate, or triflate.