Octahydronaphthalene derivatives and their preparation

Claim 2

Compounds of formula (I): [wherein: X represents a hydrogen atom or a 2-methylbutyryl group; Y represents a hydrogen atom or a methyl group; and R 1 and R 2 are the same or different and each represents an oxygen atom or a group of formula =N-OR 3 (wherein R 3 represents a hydrogen atom or an alkyl group)], the free hydroxy-carboxylic acids corresponding thereto and salts and esters of said acids.

Claim 3

Compounds as claimed in claim 1, having the formula (II): (wherein X, Y, R 1 and R 2 are as defined in claim 1) and salts and esters thereof.

Claim 4

Compounds as claimed in claim 1, having the formula (VII): wherein X, Y, R 1 and R 2 are as defined in claim 1, M represents a metal atom and n is the valency of the metal M.

Claim 5

Compounds as claimed in claim 3, wherein M represents lithium, sodium, potassium, calcium, magnesium, aluminium, iron, zinc, copper, nickel or cobalt.

Claim 6

Compounds as claimed in claim 3, wherein M represents sodium or potassium.

Claim 7

Compounds as claimed in claim 1, having the formula (YIII): wherein X, Y, R 1 and R 2 are as defined in claim 1, A represents ammonia, an organic amine or an amino acid and m is an integer.

Claim 8

Compounds as claimed in claim 6, wherein A represents arginine, lysine, histidine, 2,4-diaminobutyric acid, ornithine, ammonia, t-octylamine, benzylamine, dibenzylamine, N,N-dimethylbenzylamine, cyclohexylamine, dicyclohexylamine, N,N-dimethylcyclo- hexylamine, N-methylpyrrolidine, morpholine, an L-leucine alkyl ester, a dialkyl L-glutamate, a D-phenylglycine alkyl ester or D-glucosamine.

Claim 9

Compounds as claimed in claim 1, having the formula (IX): wherein X, Y, R 1 and R 2 are as defined in claim 1, R 8 represents the alcoholic moiety of an ester and p represents the valency of R 8.

Claim 10

Compounds as claimed in claim 8. wherein R 8 represents an alkyl group, a benzyl group, a benzyl group having at least one alkyl, alkoxy or halogen substituent, a phenacyl group or a phenacyl group having at least one alkyl, alkoxy or halogen substituent.

Claim 11

Compounds as claimed in claim 8, wherein R 8 represents a lower alkyl group.

Claim 12

Compounds as claimed in claim 8, wherein R 8 represents a methyl or ethyl group.

Claim 13

Compounds as claimed in any one of the preceding claims, wherein at least one of R 1 and R 2 represents a group of formula = N- OR 3.

Claim 14

Compounds as claimed in claim 12, in the form of a metal hydroxyimino salt of a carboxylate salt or carboxylate ester of said compound of formula (II).

Claim 15

Compounds as claimed in claim 13, wherein said metal of said hydroxyimino salt is sodium or potassium.

Claim 16

A compound as claimed in claim 1, which is: 3,4-dihydro-6-oxo-4-hydroxyiminoIsoML-236B lactone 3,4-dihydro-4-oxo-6-hydroxyiminoIsoML-236B lactone 3,4-dihydro-4,6-bis(hydroxyimino)IsoML-236B lactone sodium 3,4-dihydro-6-oxo-4-hydroxyiminoIsoML-236B carboxylate disodium 3,4-·dihydro-6-oxo-4-oxidoiminoIsoML-236B carboxylate 3,4-dihydro-6-oxo-4-methoxyimlnoIsoML-236B lactone 3,4-dihydro-6-oxo-4-hydroxyiminoIsoML-236A lactone 3,4-dihydro-4-oxo-6-hydroxyimivoIsoMB-530B lactone 3,4-dihydro-6-oxo-4-hydroxyiminoIsoMB-530B lactone 3,4-dihydro-4,6-bis(hydroxyimino)IsoMB-530B lactone or sodium 3,4-dihydro-6-oxo-4-hydroxyiminoIsoMB-530B carboxylate.

Claim 17

A process for preparing a compound as claimed in any one of the preceding claims, which process comprises the steps: (a) reacting a compound of formula (IV): (wherein Y is as defined in claim 1 and R 4 and R 5 are the same or different and each represents a hydroxy-protecting group) with an oxidising agent to give a compound of formula (V): (wherein Y, R 4 and R 5 are as defined above); (b) optionally, removing from said compound of formula (V) the hydroxy-protecting group represented by R 4 and, if necessary, removing the hydroxy-protecting group represented by R 5 , to give a compound of formula (III): (wherein X and Y are as defined above); (c) optionally, reacting a compound of formula (III) or (V) with an oximating agent of formula (XI): (wherein R 3 is as defined above) and, where said compound of formula (V) is employed, removing the protecting group represented by R 4 and, if necessary, removing the protecting group represented by R 5 , to give a compound of formula (VI): [wherein X and Y are as defined above, and R 6 and R 7 are the same or different and each represents an oxygen atom or a group of formula =N-OR 3 (wherein R 3 is as defined above), provided that R 6 and R 7 do not both represent oxygen atoms]; (d) optionally, subjecting a compound of formula (V), (III) or (VI) to salification or esterification, to give a salt or ester thereof.

Claim 18

A process as claimed in claim 16, wherein the oxidising agent in step (a) is a complex of chromic anhydride with an organic base.

Claim 19

A process as claimed in claim 17, wherein said oxidising agent is a complex of chromic anhydride with pyridine.

Claim 20

A process as claimed in any one of claims 16 to 18, wherein said oximating agent in step (c) is employed in the form of a salt with a mineral acid.

Claim 21

A process as claimed in claim 19, wherein said salt is the hydrochloride.

Claim 22

A process as claimed in any one of claims 16 to 20, wherein the amount of said oximating agent is from 1 to 1.5 equivalents per mole of said compound of formula (III) or (V), to prepare a compound of formula (VI) wherein one of R 6 and R 7 represents an oxygen atom and the other represents a group of formula =N-OR 3 .

Claim 23

A process as claimed in any one of claims 16 to 20, wherein the amount of oximating agent employed in step (c) is from 2 to 3 equivalents per mole of said compound of formula (III) or (V), to prepare a compound of formula (VI) wherein R 6 and R 7 both represent groups of formula =N-OR 3 .

Claim 24

A process for preparing a compound of formula (I): [wherein: X represents a hydrogen atom or a 2-methylbutyryl group; Y represents a hydrogen atom or a methyl group; and R 1 and R 2 are the same or different and each represents an oxygen atom or a group of formula =N-OR 3 (wherein R 3 represents a hydrogen atom or an alkyl group)], a free hydroxy-carboxylic acid corresponding thereto or a salt or ester of said acid, which process comprises the steps: (a) reacting a compound of formula (IV): (wherein Y is as defined above and R 4 and R 5 are the same or different and each represents a hydroxy-protecting group) with an oxidising agent to give a compound of formula (V): (wherein Y, R 4 and R 5 are as defined above); (b) optionally, removing from said compound of formula (V) the hydroxy-protecting group represented by R 4 and, if necessary, removing the hydroxy-protecting group represented by R 5 , to give a compound of formula (III): (wherein X and Y are as defined above); (c) optionally, reacting said compound of formula (III) or (V) with an oximating agent of formula (XI): (wherein R 3 is as defined above) and, where said compound of formula (V) is employed, removing the protecting group represented by R 4 and, if necessary, removing the protecting group represented by R 5 , to give a compound of formula (VI): [wherein X and Y are as defined above, and R 6 and R 7 are the same or different and each represents an oxygen atom or a group of formula =N-OR 3 (wherein R 3 is as defined above), provided that R6 and R7 do not both represent oxygen atoms]; (d) optionally, subjecting said compound of formula (V), (III) or (VI) to salification or esterification, to give a salt or ester thereof.

Claim 25

A process for preparing a compound of formula (I): [wherein: X represents a hydrogen atom or a 2-methylbutyryl group; Y represents a hydrogen atom or a methyl group; and R 1 and R 2 are the same or different and each represents an oxygen atom or a group of formula =N-OR 3 (wherein R 3 represents a hydrogen atom or an alkyl group)], a free hydroxy-carboxylic acid corresponding thereto or a salt or ester of said acid, which process comprises the steps: (a) reacting a compound of formula (IV): (wherein Y is as defined above and R 4 and R 5 are the same or different and each represents a hydroxy-protecting group) with an oxidising agent to give a compound of formula (V): (wherein Y, R 4 and R 5 are as defined above); (b) optionally, removing from said compound of formula (V) the hydroxy-protecting group represented by R 4 and, if necessary, removing the hydroxy-protecting group represented by R 5 , to give a compound of formula (III): (wherein X and Y are as defined above); (c) optionally, reacting said compound of formula (III) or (V) with an oximating agent of formula (XI): (wherein R 3 is as defined above) and, where said compound of formula (V) is employed, removing the protecting group represented by R 4 and, if necessary, removing the protecting group represented by R 5 , to give a compound of formula (VI): [wherein X and Y are as defined above, and R 6 and R 7 are the same or different and each represents an oxygen atom or a group of formula =N-OR 3 (wherein R 3 is as defined above), provided that R6 and R7 do not both represent oxygen atoms]; (d) optionally, subjecting said compound of formula (V), (III) or (VI) to salification or esterification, to give a salt or ester thereof.

Claim 26

A process as claimed in claim 1, wherein the oxidising agent in step (a) is a complex of chromic anhydride with an organic base.

Claim 27

A process as claimed in claim 2, wherein said oxidising agent is a complex of chromic anhydride with pyridine.

Claim 28

A process as claimed in any one of claims 1 to 3, wherein said oximating agent in step (c) is employed in the form of a salt with a mineral acid.

Claim 29

A process as claimed in claim 4, wherein said salt is the hydrochloride.

Claim 30

A process as claimed in any one of claims 1 to 5, wherein the amount of said oximating agent is from 1 to 1.5 equivalents per mole of said compound of formula (III) or (V), to prepare a compound of formula (VI) wherein one of R 6 and R 7 represents an oxygen atom and the other represents a group of formula =N-OR 3 .

Claim 31

A process as claimed in any one of claims 1 to 5, wherein the amount of oximating agent employed in step (c) is from 2 to 3 equivalents per mole of said compound of formula (III) or (V), to prepare a compound of formula (VI) wherein R 6 and R both represent groups of formula =N-O R 3 .

Claim 32

A process as claimed in any one of the preceding claims, wherein salification is effected in step (d) with a basic compound of a metal M, to prepare a compound having the formula (VII): wherein X, Y, R 1 and R 2 are as defined in claim 1, M represents a metal atom and n is the valency of the metal M.

Claim 33

A process as claimed in claim 8, wherein M represents lithium, sodium, potassium, calcium, magnesium, aluminium, iron, zinc, copper, nickel or.cobalt.

Claim 34

A process as claimed in claim 8, wherein M represents sodium or potassium.

Claim 35

A process as claimed in any one of claims 1 to 7, wherein salification in step (d) is effected with ammonia, an organic amine or an amino acid or with a salt thereof, to produce a compound having the formula (VIII): wherein X, Y, R 1 and R 2 are as defined in claim 1, A represents ammonia, an organic amine or an amino acid and m is an integer.

Claim 36

A process as claimed in claim 11, wherein A represents arginine, lysine, histidine, 2,4-diaminobutyric acid, ornithine, ammonia, t-octylamine, benzylamine, dibenzylamine, N,N-dimethylbenzylamine, cyclohexylamine, dicyclohexylamine, N,N-dimethylcyclo- hexylamine, N-methylpyrrolidine, morpholine, an L-leucine alkyl ester, a dialkyl L-glutamate, a D-phenylglycine alkyl ester or D-glucosamine.

Claim 37

A process as claimed in any one of claims 1 to 7, wherein esterification in step (d) is effected with an alcohol of formula R 8 (OH) p , to produce an ester having the formula (IX): wherein X, Y, R 1 and R 2 are as defined in claim 1, R represents the alcoholic moiety of an ester and p represents the valency of R 8 .

Claim 38

A process as claimed in claim 13 wherein R 8 represents an alkyl group, a benzyl group, a benzyl group having at least one alkyl, alkoxy or halogen substituent, a phenacyl group or a phenacyl group having at least one alkyl, alkoxy or halogen substituent.

Claim 39

A process as claimed in claim 13, wherein R 8 represents a lower alkyl group.

Claim 40

A process as claimed in claim 13, wherein R 8 represents a methyl or ethyl group.

Claim 41

A process as claimed in any one of the preceding claims, in which a compound of formula (I), (VII) or (IX) is salified with a basic compound of a metal, to produce a metal hydroxyimino salt of said compound of formula (VII) or (IX), formulae (I), (VII) and (IX) being as defined in claims 1, 8 and 13, respectively.

Claim 42

A process as claimed in claim 17, wherein said metal of said hydroxyimino salt is sodium or potassium.

Claim 43

A process as claimed in any one of claims 1 to 7, wherein ML-236B is oxidised and then reacted with hydroxylamine or a salt thereof to produce 3,4-dihydro-6-oxo-4-hydroxyiminoIsoML-236B lactone 3,4-dihydro-4-oxo-6-hydroxyiminoIsoML-236B lactone or 3,4-dihydro-4,6-bis(hydroxyimino)lsoML-236B lactone and said 3,4-dihydro-6-oxo-4-hydroxyiminoIsoML-236B is optionally salified with a basic sodium compound to produce sodium 3,4-dihydro-6-oxo-4-hydroxyiminoIsoML-236B carboxylate or disodium 3,4-dihydro-6-oxo-4-oxidoiminoIsoML-236B carboxylate.

Claim 44

A process as claimed in any one of claims 1 to 7, wherein ML-236B is oxidised and then reacted with methoxyamine or a salt thereof to produce 3,4-dihydro-6-oxo-4-methoxyiminoIsoML-236B lactone.

Claim 45

A process as claimed in any one of claims 1 to 7, wherein ML-236A is oxidised and then reacted with hydroxylamine or a salt thereof to produce 3,4-dihydro-6-oxo-4-hydroxyiminoIsoML-236A lactone.

Claim 46

A process as claimed in any one of claims 1 to 7, wherein MB-530B is oxidised and then reacted with hydroxylamine or a salt thereof to produce 3,4-dihydro-4-oxo-64-oxo-6-hydroxyiminoIsoMB-530B lactone 3,4-dihydro-6-oxo-4-hydroxyiminoIsoMB-530B lactone or 3,4-dihydro-4,6-bis(hydroxyimino)lsoMB-530B lactone and said 3,4-dihydro-6-oxo-4-hydroxyiminoIsoMB-530B is optionally salified with a basic sodium compound to produce sodium 3,4-dihydro-6-oxo-4-hydroxyiminoIsoMB-530B carboxylate.