US4514562A
Expired / Lapsed
US
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Fluorinated erythromycin compounds and a process for preparation
Assignee: Pfizer Italia SRL
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Filing: 1982-11-22
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Granted: 1985-04-30
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Expires: 2002-11-22
Abstract
Abstract Fluorinated derivatives of erythromycins A, B, C and D, having antibiotic activity, are prepared, starting from 8,9-anhydroerythromycin 6,9-hemiacetals or their N-oxides, through the reaction with a compound capable of generating electrophilic reactive fluorine, the resulting reaction product undergoing thereafter a reduction, possibly together with a methylation, to the corresponding (8S)-8-fluoroerythomycins.
Inventors
- 👤 Luciano Toscano
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 14:55
CPC Classifications
C; C07; C07H; C07H17/00; C07H17/04; C07H17/08; A; A61; A61P; A61P31/00; A61P31/04
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
115 words
A process for the preparation of (8S)-8-fluoroerthyromycins having the formula ##STR8## wherein R 1 is H or OH and R 2 is H or CH 3 comprising the following steps: (a) reacting a compound having the formula ##STR9## wherein R 1 and R 2 have the above indicated meanings and x is 0 or 1, with an electrophilic fluorine-generating compound, giving the compound having the formula ##STR10## wherein R 1 , R 2 and x have the above indicated meanings and R 3 is CH 3 , when x=1, and R 3 is H, when x=0; and (b) reducing the compound given by step (a) and, when x=0, also methylating, yielding the corresponding compounds (V).
Claim 2
Dependent Claim
115 words
A process for the preparation of (8S)-8-fluoroerthyromycins having the formula ##STR8## wherein R 1 is H or OH and R 2 is H or CH 3 comprising the following steps: (a) reacting a compound having the formula ##STR9## wherein R 1 and R 2 have the above indicated meanings and x is 0 or 1, with an electrophilic fluorine-generating compound, giving the compound having the formula ##STR10## wherein R 1 , R 2 and x have the above indicated meanings and R 3 is CH 3 , when x=1, and R 3 is H, when x=0; and (b) reducing the compound given by step (a) and, when x=0, also methylating, yielding the corresponding compounds (V).
Claim 3
Dependent Claim
23 words
A process according to claim 1, wherein said electrophilic fluorine-generating compound is perchloryl fluoride, fluoroxy-perfluoroalkanes, fluoroxy-sulphur-pentafluoride, molecular fluorine, lead tetraacetate-hydrogen fluoride or trifluoroacetylhypofluorite.
Claim 4
Dependent Claim
11 words
A process according to claim 2, wherein said compound is fluoroxytrifluoromethane.
Claim 5
Dependent Claim
12 words
A process according to claim 2, wherein said compound is perchloryl fluoride.
Claim 6
Dependent Claim
38 words
A process according to claim 1, wherein step (a) is carried out in a reaction solvent selected from the group consisting of halogenated hydrocarbons, tetrahydrofuran, tetrahydrofuran diluted with water, dioxane, dioxane diluted with water, pyridine and mixtures thereof.
Claim 7
Dependent Claim
19 words
A process according to claim 5, wherein said reaction solvent is trichlorofluoromethane, chloroform, methylene chloride, or tetrahydrofuran and water.
Claim 8
Dependent Claim
24 words
A process according to claim 1, wherein the reaction temperature is between -75° C. and -85° C. or between -10° C. and +10° C.
Claim 9
Dependent Claim
18 words
A process according to claim 1, wherein said fluorination is carried out in the presence of a base.
Claim 10
Dependent Claim
21 words
A process according to claim 1, wherein said reduction is carried out by hydrogenation in the presence of a hydrogenation catalyst.
Claim 11
Dependent Claim
14 words
A process according to claim 9, wherein said catalyst is palladium supported on charcoal.
Claim 12
Dependent Claim
16 words
A process according to claim 9, wherein said reduction is carried out in a reaction solvent.
Claim 13
Dependent Claim
15 words
A process according to claim 10, wherein said reduction is carried out at room temperature.
Claim 14
Dependent Claim
18 words
A process according to claim 10, wherein said reduction is carried out at 1 atm. of hydrogen pressure.
Claim 15
Dependent Claim
19 words
A process according to claim 1, wherein said reduction is carried out in the presence of a methylating agent.
Claim 16
Dependent Claim
12 words
A process according to claim 14, wherein said methylating agent is formaldehyde.
Claim 17
Dependent Claim
23 words
A process according to claim 11, wherein said reaction solvent is selected from the group consisting of ethanol, methanol, tetrahydrofuran and ethyl acetate.
Claim 18
Dependent Claim
16 words
A process according to claim 8, wherein said base is calcium oxide, pyridine or potassium acetate.
Claim 19
Dependent Claim
50 words
A process according to claim 1, wherein said reduction is carried out in the presence of a hydrogenation catalyst comprising palladium supported on charcoal, in a reaction solvent selected from the group consisting of ethanol, methanol, tetrahydrofuran and ethyl acetate and in the presence of a methylating agent comprising formaldehyde.
Claim 20
Dependent Claim
20 words
(8S)-8-fluoroerythromycin N-oxides having the formula: ##STR11## wherein R 1 is hydrogen or OH, and R 2 is hydrogen or methyl.
Claim 21
Dependent Claim
20 words
(8S)-8-fluoroerythromycin N-oxides having the formula: ##STR11## wherein R 1 is hydrogen or OH, and R 2 is hydrogen or methyl.
Claim 22
Dependent Claim
7 words
(8S)-8-fluoroerythromycin A N-oxide according to claim 19.
Claim 23
Dependent Claim
7 words
(8S)-8-fluoroerythromycin B N-oxide according to claim 19.
Claim 24
Dependent Claim
7 words
(8S)-8-fluoroerythromycin C N-oxide according to claim 19.
Claim 25
Dependent Claim
7 words
(8S)-8-fluoroerythromycin D N-oxide according to claim 19.
Claim 26
Dependent Claim
19 words
de-(N-methyl)-(8S)-8-fluoroerythromycins having the formula: ##STR12## wherein R 1 is hydrogen or OH, and R 2 is hydrogen or methyl.
Claim 27
Dependent Claim
19 words
de-(N-methyl)-(8S)-8-fluoroerythromycins having the formula: ##STR12## wherein R 1 is hydrogen or OH, and R 2 is hydrogen or methyl.
References Cited (Backward Citations)
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1988-04-29 | 1988-10-29 | 1989-04-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-04-29 | 1992-10-29 | 1993-04-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-04-29 | 1996-10-29 | 1997-04-30 | $7700.00 | Window Closed / Lapsed |