5-O-deosaminyl 6-O-methyl erythronolide A derivatives,...

Details 5-O-deosaminyl 6-O-methyl erythronolide A derivatives,... 5-O-deosaminyl 6-O-methyl erythronolide A derivatives,...

2001-01-29

2004-02-10

Wilson, James O. (Department: 1623)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

C536S007200, C514S029000

Reissue Patent

active

RE038426

ABSTRACT:

This application is a 371 of PCT/FR96/01567 filed on Oct. 8, 1996.
The present invention relates to new derivatives of 5-O-desosaminyl 6-O-methyl erythronolide A, their preparation process and their use in the preparation of biologically active products.
A subject of the invention is the compounds of formula (I):
in which R represents a carboxylic acid remainder containing up to 18 carbon atoms.
Among the carboxylic acid remainders, there can in particular be mentioned the acetyl, propionyl, butyryl, isobutyryl, n-valeryl, isovaleryl, tert-valeryl and pivalyl radicals.
A more particular subject of the invention is the compounds of formula (I) in which R represents an acetyl radical.
A subject of the invention is also a preparation process characterized in that a compound of formula (II):
in which R retains its previous meaning, is subjected to the action of an agent capable of selectively activating the hydroxyl in position 11, then to the action of a base to obtain the compound of formula (III):
which is subjected to the action of carbonyldiimidazole, then to the action of the hydrazine NH
2
NH
2
to obtain the corresponding compound of formula (I).
The compounds of formula (II) we known in a general way and can be prepared according to the process described in European Patent Application 619319.
In a preferred implementation,
the agent capable of selectively activating the hydroxyl in position 11 is a sulphonic add derivative such as methanesulphonic, paratoluenesulphonic, trifluoromethanesulphonic anhydride or thionyl chloride SOCl
2
, which forms a cyclic sulphite with the OH function in position 12,
the base used to produce a 10(11) double bond is a diazabicycloundecene, for example DBU (or 1,8-diazabicyclo-[5-4-0]undec-7-ene), or DBN (or 1,5-diazabicydo[4,3,0]non-5-ene or 2,6-lutidine, a 2,4,6-collidine or tetramethyl-guanidine,
the reaction of the compound of formula (III) with carbonyldiimidazole takes place in the presence of one of the bases mentioned above or also in the presence of sodium hydride, triethylamine, sodium or potassium carbonate or bicarbonate. NaN(SiMe
2
)
2
a LiN(SiMe
3
)
2
,
the hydrazine is used in the form of hydrazine hydrate.
The obtained compounds of formula (III) are new products and are themselves a subject of the present invention.
The subject of the invention is therefore, as chemical products, the compounds of formula (III) and quite particularly the compound of formula (III) in which R represents an acetyl radical.
The compounds of formula (I) are useful intermediate products which can in particular lead to the preparation of antibiotic products, described and claimed in European Patent Application 0,676,409.
In particular, a subject of the invention is the use, characterised in that a compound of formula (I) is subjected to the action of a cleaving agent of the protected hydroxyl functions to obtain the compound of formula (IV):
which is subjected to the action of an aldehyde of formula (V):
in which R′
1
represents a hydrogen atom or a saturated or unsaturated hydrocarbon radical containing up to 23 carbon atoms, optionally interrupted by one or more heteroatoms and optionally having one or more functional groups, to obtain the compound of formula (VI):
which is subjected to the action of an oxidizing agent of the hydroxyl in position 3 then to the action of a cleaving agent of the hydroxyl in position 2′ to obtain the compound of formula (VII):
which is subjected to the action of a reducing agent to obtain the corresponding compound of formula (VIII):
in which R′
1
retains its previous meaning.
In a preferred implementation,
R′
1
represents the radical
cleavage of the protected hydroxyl functions is carried out by saponification then acidification of the ester function,
esterification of the hydroxyl function in position 2′ is carried out according to standard processes,
oxidation of the hydroxyl in position 3 is carried out using a diimide in the presence of DMSO, for example the hydrochloride of 1-ethyl 3-(3-dimethylamino propyl) carbodiimide,
cleavage of the hydroxyl in position 2′ takes place by methanolysis,
the reducing agent is NaBH
3
CN or NaBH(OAc)
3
or also NaBH
4
in the presence of acetic acid or hydrogen in the presence of a catalyst such as palladium, platinum and optionally in the presence of an acid such as hydrochloric acid or acetic acid.
The products of formula (VII) are products having useful antibiotic properties, described and claimed in European Patent 0,676,409.


REFERENCES:
patent: 3923784 (1975-12-01), Kierstead et al.
patent: 4518590 (1985-05-01), Hauske et al.
patent: 4742049 (1988-05-01), Baker et al.
patent: 4921839 (1990-05-01), Brain et al.
patent: 5631355 (1997-05-01), Asaka et al.
patent: 0619320 (1994-10-01), None
patent: 0638585 (1995-02-01), None
patent: 0682038 (1995-11-01), None
Journal of Medicinal Chemistry, vol. 18, No. 8, pp. 849-851, 1975.

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