Hydroxy derivatives of tylosin and process for their preparation
AssigneePLIVA, farmaceutska industrija, dionicko drustvo
InventorsAmalija Narandja, Nevenka Lopotar, Zoran Mandić
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Abstract
The present invention relates to 12,13-dihydroxy derivatives of tylosin, new semisynthetic compounds of the macrolide class, and to a process for their preparation. According to the present invention by the oxidation of 13-hydroxy derivative a 12,13-dihydroxy compound is obtained, which can be subsequently subjected to a series of reactions such as oximation, reduction (catalytic, electrochemical) or hydrolysis yielding corresponding dihydro or tetrahydro 12,13-dihydroxy derivatives.
Claims23
12,13-dihydroxy derivative of tylosin of the formula (I)
- wherein
- R represents O, R1 represents CHO, CH═NOH or CH(OCH3)2, R2 represents H or mycarosyl, R3 represents N(CH3)2 or NO(CH3)2, and - - - line represents a single or a double bond, with the proviso that R3 represents N(CH3)2 when - - - line represents a single bond;
- or
- wherein
- R represents NOH, R1 represents CHO or CH(OCH3)2, R2 represents H or mycarosyl, R3 represents N(CH3)2 or NO(CH3)2, and - - - line represents a single or a double bond, with the proviso that R3 represents N(CH3)2 when - - - line represents a single bond.
A process for the preparation of a 12,13-dihydroxy tylosin derivative of the formula (I):
- wherein
- R represents O, R1 represents CHO, CH═NOH or CH(OCH3)2, R2 represents H or mycarosyl, R3 represents N(CH3)2 or NO(CH3)2 and - - - line represents a single or a double bond, with the proviso that R3 represents N(CH3)2 when - - - line represents a single bond;
- or
- wherein
- R represents NOH, R1 represents CHO or CH(OCH3)2, R2 represents H or mycarosyl, R3 represents N(CH3)2 or NO(CH3)2 and - - - line represents a single or a double bond, with the proviso that R3 represents N(CH3)2 when - - - line represents a single bond, wherein a compound of the formula (II):
- wherein R represents H or mycarosyl, is subjected to an oxidation reaction, yielding a tylosin derivative having the formula I, wherein R represents O, R1 represents CH(OCH3)2, R2 represents H or mycarosyl, R3 represents NO(CH3)2, and - - - line represents a double bond, said tylosin derivative is optionally subjected:
- A/ to a reduction of N-oxide;
- or optionally
- B/ to a reduction of N-oxide and C10-C11 double bond;
- or optionally
- C/ to an oximation reaction;
- or optionally
- a compound of formula (I), wherein R represents NOH, R1 represents CH(OCH3)2, R2 represents H or mycarosyl, R3 represents NO(CH3)2, and - - - line represents a double bond, is subjected to a reduction of N-oxide;
- or optionally
- to a reduction of N-oxide and C10-C11 double bond by catalytic hydrogenation;
- or optionally
- a compound of the formula (I), wherein R represents O, R1 represents CH(OCH3)2, R2 represents H or mycarosyl, R3 represents N(CH3)2, and - - - line represents a single or a double bond, is subjected to an oximation reaction;
- or optionally
- a compound of formula (I), wherein R represents NOH, R1 represents CH(OCH3)2, R2 represents H or mycarosyl, R3 represents N(CH3)2, and - - - line represents a single or a double bond, subjected to hydrolysis.
Dependencies are inferred from the claim text.