In an effort to synthesize a key intermediate, for synthesis of a variety of telithromycin derivatives a new by-product has been formed at the third stage of the synthetic scheme. The starting material, Clarithromycin, on treatment with hydrochloric acid and on benzoylation resulted in the formation of (3
R,4
S,5
S,6
R,7
R,9
R,11
R,12
R,13
S,14
R)-14-ethyl-4,12,13-trihydroxy-7-methoxy- 3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecan-6-yl 3,4,6-trideoxy- 3-(dimethylamino)-2
-O-(phenylcarbonyl)-β-D-
xylo-hexopyranoside (
2). Oxidation of this gave (3
R,5
R,6
R,7
R,9
R,11
R,12
R,13
S,14
R)-14-ethyl-12,13-dihydroxy- 7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradecan-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2
-O-(phenylcarbonyl)-β-D-
xylo-hexopyranoside (
3), and also an unexpected by-product 4 in equivalent amounts. The O21–H hydroxyl group in 3 was mesylated with dimethyl sulphoxide (DMSO) in pyridine leading to the precursor (3
R,5
R,6
R,7
R,9
R,11
R,12
R,13
S,14
R)-14-ethyl- 12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-12-(methylsulfinyl)- 2,4,10-trioxooxacyclotetradecan-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2
-O- (phenylcarbonyl)-β-D-
xylo-hexopyranoside (
5), which on further treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetone and methylene chloride resulted in the formation of intermediate
6. The by-product
4 and the intermediate
6 were isolated and characterized as (1
S,2
R,5
R,7
R,8
R,9
R)-2- ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,6-dioxo-3,15-dioxabicyclo[10.2.1]- pentadeca-11,13-dien-8-yl 3,4,6-trideoxy-3-(dimethylamino)-2
-O-(phenylcarbonyl)- β-D-
xylo-hexopyranoside (
4) and (3
R,5
R,6
R,7
R,9
R,11E,13S,14
R)-14- ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradec- 11-en-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2
-O-(phenylcarbonyl)-β-D
xylo- hexopyranoside (
6) respectively by 2D NMR and single crystal X-ray diffraction.
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