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US 2007/0167630 A1Published application
Method for producing pentacyclic taxans
AssigneeDaiichi Pharmaceutical Co., Ltd.
InventorsAkihiro Imura, Tatsuya Yamaguchi, Yoshihiro Takayanagi, Seishiro Uchida
Life of this patent
Estimating the term…
Abstract
Taxan derivatives are produced efficiently and inexpensively, which are useful as oral-administrable antitumor compounds. A compound of formula (1) (wherein R1 is an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group; R2 is a hydroxyl group optionally having a protective group) is processed with an alkali metal permanganate to produce a compound of formula (2), which may be a starting material for oral-administrable antitumor compounds.
Claims22
A method for producing a compound of the following general formula (2) or its salt, or their hydrate or solvate, which comprises reacting a compound of the following formula (1) with an alkali metal permanganate:
- (in formula (1), the dot line part between the 6-position and the 7-position of the partial structure of the following formula (1-a):
- means that the bond of this part may be a double bond;
- boc means a tert-butoxycarbonyl group;
- Ac means an acetyl group;
- Bz means a benzoyl group;
- R1 means an alkyl group, an alkenyl group, an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the aryl group or the heterocyclic group may be have one or more substituents selected from a group consisting of a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxy group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group;
- R2 means a hydroxyl group optionally having a protective group);
- (in formula (2), R1, R2, boc, Ac and Bz have the same meanings as above).
5 more elements
A method for producing a compound of the following general formula (3) or its salt, or their hydrate or solvate, which comprises;
- 1) a step of reacting a compound of the following general formula (1):
- (in formula (1), the dot line part between the 6-position and the 7-position of the partial structure of the following formula (1-a):
- means that the bond of this part may be a double bond;
- boc means a tert-butoxycarbonyl group;
- Ac means an acetyl group;
- Bz means a benzoyl group;
- R1 means an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the aryl group or the heterocyclic group may be have one or more substituents selected from a group consisting of a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxy group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group;
- R2 means a hydroxyl group optionally having a protective group), with an alkali metal permanganate to obtain a compound of the following general formula (2):
- (in formula (2), R1, R2, boc, Ac and Bz have the same meanings as above);
- 2) a step of converting the group —CH(OH)CH2OH in the compound of formula (2) into a group —R3 {in which R3 means a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, an aryl group or a heterocyclic group, and the alkyl group, the alkenyl group, the alkynyl group, the aryl group or the heterocyclic group may have one or more substituents selected from a group consisting of an alkoxy group, an amino group, an alkylamino group, an aminoalkyl group, an alkylaminoalkyl group, a cycloalkylamino group and a nitrogen-containing, 5-membered or 6-membered saturated heterocyclic group of the following formula (3-a):
- (in formula (3-a), X means an oxygen atom, a sulfur atom, CH2, CH—Y, NH or N—Y;
- and Y means an alkyl group),
- (the heterocyclic group may have one or more alkyl groups on the carbon atom that constitutes the ring)};
- 3) when the bond between the 6-positioned carbon and the 7-positioned carbon is a double bond, a step of converting it into a single bond;
- and
- 4) when R2 is a hydroxyl group having a protective group, a step of removing the protective group:
- (in formula (3), R1, R3, boc, Ac and Bz have the same meanings as above).
14 more elements
A compound of the following general formula (12) or its salt, or their hydrate or solvate:
- (in formula (12), R7 means a halogen atom or an alkoxy group;
- n indicates an integer of from 0 to 4;
- when n is 2 or more, then two or more R7's may be the same or different;
- R8 means an alkyl group, an aryl group or an alkoxy group, and the alkyl group, the aryl group or the alkoxy group may have one or more substituents selected from a group consisting of a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxy group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group;
- R9 means a hydroxyl group optionally having a protective group;
- R10 means an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the aryl group or the heterocyclic group may have one or more substituents selected from a group consisting of a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxy group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group).
3 more elements
A method for producing a compound of the following formula (16) or its salt, or their hydrate or solvate, which comprises reacting a compound of the following general formula (12):
- (in formula (12), R7 means a halogen atom or an alkoxy group;
- n indicates an integer of from 0 to 4;
- when n is 2 or more, then two or more R7's may be the same or different;
- R8 means an alkyl group, an aryl group or an alkoxy group, and the alkyl group, the aryl group or the alkoxy group may have one or more substituents selected from a group consisting of a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxy group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group;
- R9 means a hydroxyl group optionally having a protective group;
- R10 means an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group or a heterocyclic group, and the alkyl group, the alkenyl group, the alkynyl group, the cycloalkyl group, the aryl group or the heterocyclic group may have one or more substituents selected from a group consisting of a halogen atom, a hydroxyl group, a carboxyl group, an alkyl group, an alkoxy group, a phenyl group, an amino group, an alkylamino group, an aminoalkyl group, an alkylaminoalkyl group, an alkoxycarbonyl group, an aryloxycarbonyl group, an acyl group, an acylamino group and an acyloxy group), with a compound of the following formula (15):
- (in formula (15), the dot line part between the 6-position and the 7-position of the partial structure of the following formula (15-a):
- means that the bond of this part may be a double bond;
- Ac means an acetyl group;
- Bz means a benzoyl group),
- to produce a compound of the following formula (16) or its salt, or their hydrate or solvate:
- (in formula (16), R7, R8, R9, n, Ac and Bz have the same meanings as above).
9 more elements
A method for producing a compound of the following general formula (11) or its salt, or their hydrate or solvate, which comprises reacting a compound of the following general formula (14):
- (in formula (14), boc means a tert-butoxycarbonyl group;
- TIPS means a triisopropylsilyl group),
- with a compound of the following general formula (19):
- (in formula (19), Ac means an acetyl group;
- and Bz means a benzoyl group),
- to produce a compound of the following general formula (7):
- (in formula (7), boc, TIPS, Ac and Bz have the same meanings as above),
- then reacting the compound of formula (7) with potassium permanganate in the presence of lithium hydroxide in aqueous pyridine to obtain a compound of the following general formula (8):
- (in formula (8), boc, TIPS, Ac and Bz have the same meanings as above),
- reacting the compound of formula (8) with an alkali metal periodate and then with sodium acetoxyborohydride in the presence of acetic acid and dimethylamine to obtain a compound of the following general formula (9):
- (in formula (9), boc, TIPS, Ac and Bz have the same meanings as above),
- and then reacting the compound of formula (9) with a palladium-carbon catalyst in the presence of hydrogen gas to thereby reduce the compound of formula (9) into a compound of the following general formula (10):
- (in formula (10), boc, Ac, Bz and TIPS have the same meanings as above),
- and thereafter reacting the compound of formula (10) with a fluoroammonium salt to produce a compound of the following general formula (11) or its salt, or their hydrate or solvate:
- (in formula (11), boc, Ac and Bz have the same meanings as above).
12 more elements
A method for producing a compound of the following general formula (11) or its salt, or their hydrate or solvate, which comprises reacting a compound of the following general formula (14):
- (in formula (14), boc means a tert-butoxycarbonyl group;
- TIPS means a triisopropylsilyl group),
- with a compound of the following general formula (19):
- (in formula (19), Ac means an acetyl group;
- and Bz means a benzoyl group) to produce a compound of the following general formula (7):
- (in formula (7), boc, Ac, Bz and TIPS have the same meanings as above),
- then reacting the compound of formula (7) with potassium permanganate in aqueous pyridine to obtain a compound of the following general formula (8):
- (in formula (8), boc, Ac, Bz and TIPS have the same meanings as above),
- reacting the compound of formula (8) with an alkali metal periodate, and then with sodium acetoxyborohydride in the presence of acetic acid and dimethylamine to obtain a compound of the following general formula (9):
- (in formula (9), boc, Ac, Bz and TIPS have the same meanings as above),
- and then reacting the compound of formula (9) with a palladium-carbon catalyst in the presence of hydrogen gas to thereby reduce the compound of formula (9) into a compound of the following general formula (10):
- (in formula (10), boc, Ac, Bz and TIPS have the same meanings as above), and thereafter reacting the compound of formula (10) with a fluoroammonium salt to produce a compound of the following general formula (11) or its salt, or their hydrate or solvate:
- (in formula (11), boc, Ac and Bz have the same meanings as above).
10 more elements
Dependencies are inferred from the claim text.