Claims
- 1. An Erythromycin A derivative represented by the formula: ##STR17## wherein R' is a group of the formula R.sup.7 CH.sub.2 -- (wherein R.sup.7 is a hydrogen atom or an alkyl group having 1 to 3 carbon atoms) or a group of the formula R.sup.8 O (wherein R.sup.8 is an alkyl group having 1 to 6 carbon atoms), R.sup.2 is R.sup.8, a cycloalkyl group having 5 to 7 carbon atoms, a phenyl group or an aralkyl group, or R.sup.2 and R.sup.7 together form an alkylene group having 2 or 3 carbon atoms, R.sup.3 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a phenyl group or an aralkyl group, or R.sup.3 and R.sup.7 together form an alkylene group having 3 to 5 carbon atoms or an alkylene group having 3 to 5 carbon atoms and substituted by 1 to 3 alkyl groups having each 1 to 3 carbon atoms, or R.sup.2 and R.sup.3 together form an alkylene group having 3 or 4 carbon atoms, R.sup.4 is an alkyl group having 1 to 3 carbon atoms, R.sup.5 is a substituted silyl group of formula --SiR.sup.9 R.sup.10 R.sup.11 (wherein R.sup.9, R.sup.10 and R.sup.11 are the same or different, and each is a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a phenyl substituted alkyl group in which the alkyl moiety has 1 to 3 carbon atoms, a phenyl group, a cycloalkyl group having 5 to 7 carbon atoms or an alkenyl group having 2 to 5 carbon atoms, with the proviso that at least one of R.sup.9, R.sup.10 and R.sup.11 is other than hydrogen atom), and R.sup.6 is a hydrogen atom or R.sup.5.
- 2. An Erythromycin A derivative represented by the formula: ##STR18## wherein R.sup.1 is a group of the formula R.sup.7 CH.sub.2 -- (wherein R.sup.7 is a hydrogen atom of an alkyl group having 1 to 3 carbon atoms) or a group of the formula R.sup.8 O-- (wherein R.sup.8 is an alkyl group having 1 to 6 carbon atoms), R.sup.2 is R.sup.8 , a cycloalkyl group having 5 to 7 carbon atoms, a phenyl group or an aralkyl group, or R.sup.2 and R.sup.7 together form an alkylene group having 2 or 3 carbon atoms, R.sup.3 is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, a phenyl group or an aralkyl group, or R.sup.3 and R.sup.7 together form an alkylene group having 3 to 5 carbon atoms or an alkylene group having 3 to 5 carbon atoms and substituted by 1 to 3 alkyl groups having each 1 to 3 carbon atoms, or R.sup.2 and R.sup.3 together form an alkylene group having 3 or 4 carbon atoms, R.sup.5 is a substituted silyl group of formula --SiR.sup.9 R.sup.10 R.sup.11 (wherein R.sup.9, R.sup.10 and R.sup.11 are the same or different, and each is a hydrogen atom, an alkyl group having 1 to 15 carbon atoms, a phenyl substituted alkyl group in which the alkyl moiety has 1 to 3 carbon atoms, a phenyl group, a cycloalkyl group having 5 to 7 carbon atoms or an alkenyl group having 2 to 5 carbon atoms, with the proviso that at least one of R.sup.9, R.sup.10 and R.sup.11 is other than hydrogen atom), and R.sup.6 is a hydrogen atom or R.sup.5.
- 3. 2',4"-O-bis(trimethylsilyl)-erythromycin A 9-{O-[1-(1-methylethoxy)cyclohexyl]oxime}.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 61-300653 |
Dec 1986 |
JPX |
|
CROSS REFERENCE TO THE RELATED APPLICATION
This is a continuation-in-part application of U.S. Ser. No. 132,258 filed Dec. 14, 1987, now abandoned.
1. Field of the Invention
The present invention relates to erythromycin A derivatives and a method for the preparation of the same.
2. Description of the Prior Art
6-O-Alkylerythromycins are useful as anti-bacterial agents or intermediates for synthesis of the antibacterial agents. For example, 6-O-methylerythromycin A is not only stable under acidic conditions but also has a strong antibacterial activity when compared with erythromycin A. Especially, this compound shows an excellent effect in treatment of infections by oral administration, and therefore it is a useful antibacterial agent.
There are known in the past several methods for preparing 6-O-methylerythromycin A, for example, (1) a method which comprises substituting the hydrogen atom of the hydroxy group at the 2'-position and the methyl group of the dimethylamino group at the 3'-position of the erythromycin A derivatives by benzyloxycarbonyl group, whereafter, carrying out methylation of the hydroxy group at the 6-position, elimination of the benzyloxy carbonyl group, and methylation of the methylamino group at the 3'-position (U.S. Pat. No. 4,331,803), and (2) an improved method for the selective methylation of the hydroxy group at the 6-position of erythromycin A derivatives which comprises converting erythromycin A derivatives having the protected hydroxy group at the 2'-position and/or the protected dimethylamino group at the 3'-position into the various kinds of the substituted oxime derivative, whereafter, carrying out methylation of the hydroxy group at the 6-position, elimination of the protecting groups, deoximation at the 9-position and reproduction of the dimethylamino group at the 3'-position to give 6-O-methylerythromycin A (European Pat. No. 158,467).
However, since erythromycin A has many hydroxy groups, there are obtained various kinds of erythromycin A derivatives which are methylated at hydroxy other than the 6-position as the by-products by the method of item (1). Accordingly, this method requires a complicated procedure for purification of the 6-O-methylerythromycin A derivative, and has the drawback of giving a low yield of said derivative. Although it is possible to methylate selectively the 6-hydroxy group by the method of item (2), this method requires complicated procedures such as catalytic reduction for elimination of the protecting groups after methylation.
As a result of research to solve the drawbacks of the above known methods, the present inventors have found a method for the preparation of 6-O-alkylerythromycin A derivatives by which the hydroxy group at the 6-position of erythromycin A derivatives can be methylated selectively, and introduction and elimination of the protecting groups can be easily carried out.
US Referenced Citations (2)
| Number |
Name |
Date |
Kind |
| 4640910 |
Faubl et al. |
Feb 1987 |
|
| 4670549 |
Morimoto et al. |
Jun 1987 |
|
Foreign Referenced Citations (3)
| Number |
Date |
Country |
| 0158467 |
Oct 1985 |
EPX |
| 0201166 |
Nov 1986 |
EPX |
| 0222353 |
May 1987 |
EPX |
Continuations (1)
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Number |
Date |
Country |
| Parent |
132258 |
Dec 1987 |
|
Patent Grant
4990602
