Reacción #740164

ord-845e272480e8414691e6782ea896d4f9

Ecuación de reacción

CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@](C)(O)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O
erythromycin A
C[C@@H](O)C[C@@H]([C@@H](O)C=O)N(C)C
desosamine
FOC(F)(F)F
trifluoromethyl hypofluorite
→
CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@](C)(O)C[C@](C)(F)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O
(8S)-8-fluoroerythromycin A
Rendimiento 35.0%

Reactantes

—
N-oxide
CC[C@H]1OC(=O)[C@H](C)[C@@H](O[C@H]2C[C@@](C)(OC)[C@@H](O)[C@H](C)O2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@](C)(O)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@]1(C)O
erythromycin A
C[C@@H](O)C[C@@H]([C@@H](O)C=O)N(C)C
desosamine
—
sugar
—
( 3 )
—
perchloryl fluoride
FOC(F)(F)F
trifluoromethyl hypofluorite
—
enol-ether
—
( 2 )

Reactivos

Ninguno

Condiciones de reacción

Condiciones detalladas
See reaction.notes.procedure_details.

Procedimiento

According to such a synthesis an enol-ether function (2) is generated in the molecule of erythromycin A (1) and subsequently the N-dimethyl group of desosamine is protected as N-oxide (3) to avoid the partial or total N-demethylation of the basic sugar during the fluorination; fluorination of (3) with trifluoromethyl hypofluorite or perchloryl fluoride, followed by hydrogenolysis, gives (8S)-8-fluoroerythromycin A (5). As a matter of fact, by operating according to the disclosure of the second Application erythromycin A can be converted into (8S)-8-fluoroerythromycin A, with a yield of about 35% in four subsequent steps (scheme II):

Fuente

DOI: 10.6084/m9.figshare.5104873.v1Patente: US04673736uspto-grants-1987_06