Patent EA-000575-B1 (EA)
Title: Novel 5-o-deoaminyl 6-o-methyl erythronolide a derivatives, method for preparing same and application thereof for preparing biologically active products
Inventor: BONNET ALAIN
IPC: C07H17/08
Filed: 1996-09-10
Abstract: 1. A compound of formula (I):   wherein or R1 is radical alkyl comprising up to 8 carbon atoms, substituted by one or a plurality of radical alkyl comprising up to 14 carbon atoms, or R1 is radical aryl comprising upto 14 carbon atoms, which can be substituted by one or a plurality of radical alkyl, alkenyl or alkynyl, comprising upto 8 carbon atoms, nitro, CF3 or one or a plurality of halogen atoms, or R1 is radical:   in which Ra is radical alkyl or alkoxy comprising upto 8 carbon atoms, Rb is radical alkyl comprising upto 8 carbon atoms, which can be substituted by a hetreroatom Rc is a hydrogen atom orradical alkyl comprising upto 8 carbon atoms R2 and R3, identical or different, are radical trialkylsilyl, in which radical alkyl comprises upto 8 carbon atoms   wherein R'a, R'b, R'c and Rd are alkyl radicals, comprising upto 8 carbon atoms, or radical aralkyl, coprising upto 8 carbon atoms, which can be substituted by one or a plurality of substituents, defined above for R1. 2. Compounds according to Claim 1 of fornula (I), wherein R1 is radical   wherein Ra, Rb and Rc have values, defined in Claim. 3. Compounds according to Claim 2 of formula (I) wherein Ra, Rb and R are radical methyl. 4. Compounds according to Claims 1-3 of formula (I) wherein R2 and R3, are both radical trialkylsilyl. 5. Compounds according to Claim 4 of formula (I) wherein R2 and R3, are radical trimethyllsilyl. 6. Compounds according to Claim 1 of formula (I) comprising 9-0-(1-methoxy-1-methylethyl) oxime 3-0 -de(2,6-dideoxy-3-C-methyl -3-0-methyl-alpfa-L-ribo-hexopuranozyl)-2'0, 3-0-bis(trimethylsilyl)-6-0-methllerythromicine, 7. Method for preparing compounds of formula (I), as defined in one of Claims 1-6, wherein a compound of formula (II):   is subjected to the action of an agent for blocking oxime to obtain a compound (III):   wherein R1 has a value defined above, which is subjected to the action of an agent for blocking hydroxyl in position 3 and in the position 2' to obtain formula (IV):   wherein R1, R2 and R3 have values defined above, which is treated with an agent for methylation of hydroxyl in position 6 to obtain a compound of formula (I): 8. Method according to Claim 7, wherein metilation of formula (IV) is realized out using methyliodide in the presence of the base. 9. Compound of formula:   wherein R1 has values as defined in Claim 1, R2', and R3' are H or have values, defined for R2 and R3 in Claim 1. 10. Compounds according to Claim 9, comprising the following products: 9-0-(1-methoxy-1-methylethyl) oxime 3-0 -de(2,6-dideoxy-3-C-methyl -3-0-methyl-alpfa-L-ribo-hexopuranozyl)-2'0, 3-0-bis(trimethylsilyl)erythromicine,. 11. Method for preparing compounds of formula VI: wherein Z is a protection group such as carbonic acid residue, comprising upto 8 carbon atoms, radical trialkylsilyl, tret butyl and triphenylmethyl, wherein a compound of formula (1) of Claim 1 are subjected to operations, which are: - liberation of oxime in position 9,- - liberation of hydroxyl in position 3 and 2', - protection of hydroxyl in position 2'. 12. Method of Claim 11, wherein a compound of formula (I) is subjected to action of formic acid in the presence of sodium bisulfite or sodium metabisulfite to obtain directly a compound of formula (V)   which is subjected to the action of a protection agent of hydroxyl group in position 2' to obtain a compound of formula (VI). 13. Method of Claim 11, wherein a compound of formula (I) is subjected to action of hydroxyl liberation in position 3 and in position 2' to obtain a compound of formula (VII):   wherein R1 has a value, defined in Claim 1, which is subjected to the action of a protection agent of group OH in position 2' to obtain a compound of formula (VIII):   wherein R1 has the value, defined above, and Z is a protection group, which is subjected to the action of an agent for liberation group 9-oxo to obtain a compound of formula (VI).