US4149007A
Expired / Lapsed
US
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C14 Phenyl-substituted derivatives of prostaglandin analogues
Assignee: Bayer Corp
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Filing: 1977-06-23
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Granted: 1979-04-10
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Expires: 1997-06-23
Abstract
Abstract Analogues of prostaglandins A, E and F in which a phenyl moiety is attached to the C14 carbon atom are disclosed. Also disclosed are methods of preparing the analogues and starting materials. The compounds have the structural formula: <IMAGE> in which J is methylene, R or S-hydroxymethylene or methine; L is methylene or methine and can be methine only when J is methine; M is carbonyl, R or S-hydroxymethylene; Q is ethylene, Z-vinylene or inter-phenylene; T is an alkoxy-carbonyl having from 2 to 3 carbon atoms inclusive, or carboxyl; and B is a loweralkyl of from 1 to 5 carbon atoms.
Inventors
- 👤 Robert T. Buckler
- 👤 David L. Garling
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-10 02:28
CPC Classifications
C; C07; C07C; C07C405/00; C07C33/00; C07C33/40; C07C33/46; C07C33/48; C07C33/483; C07F; C07F1/00; C07F1/08
Claims Analysis
Total Claims: 63
Claim 1
Independent Claim
102 words
A compound having the formula ##STR55## wherein: J is selected from the group consisting of methylene, R-hydroxymethylene, S-hydroxymethylene and methine; L is selected from the group consisting of methylene and methine with the proviso that L is methine only when J is methine; M is selected from the group consisting of carbonyl, R-hydroxymethylene and S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 2
Dependent Claim
102 words
A compound having the formula ##STR55## wherein: J is selected from the group consisting of methylene, R-hydroxymethylene, S-hydroxymethylene and methine; L is selected from the group consisting of methylene and methine with the proviso that L is methine only when J is methine; M is selected from the group consisting of carbonyl, R-hydroxymethylene and S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 3
Dependent Claim
67 words
A compound having the formula: ##STR56## wherein: J is selected from the group consisting of methylene and R-hydroxymethylene or S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 4
Dependent Claim
67 words
A compound having the formula: ##STR56## wherein: J is selected from the group consisting of methylene and R-hydroxymethylene or S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 5
Dependent Claim
24 words
A compound according to claim 2, wherein J is R-hydroxymethylene or S-hydroxymethylene and Q is selected from the group consisting of ethylene and inter-phenylene.
Claim 6
Dependent Claim
25 words
A compound according to claim 2 and enantiomers thereof, wherein J is methylene and Q is selected from the group consisting of ethylene and inter-phenylene.
Claim 7
Dependent Claim
25 words
A compound according to claim 2 and enantiomers thereof, wherein J is methylene and Q is selected from the group consisting of ethylene and inter-o-phenylene.
Claim 8
Dependent Claim
16 words
A compound according to claim 2 wherein J is R-hydroxymethylene or S-hydroxymethylene and Q is Z-vinylene.
Claim 9
Dependent Claim
17 words
A compound according to claim 2 and enantiomers thereof, wherein J is methylene and Q is Z-vinylene.
Claim 10
Dependent Claim
45 words
A compound having the formula: ##STR57## wherein: Q is ethylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 11
Dependent Claim
45 words
A compound having the formula: ##STR57## wherein: Q is ethylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 12
Dependent Claim
42 words
A compound having the formula: ##STR58## wherein: T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 13
Dependent Claim
42 words
A compound having the formula: ##STR58## wherein: T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 14
Dependent Claim
2 words
Methyl 14-phenyl-11α,15S-dihydroxy-9-oxoprost-13E-en-1-oate.
Claim 15
Dependent Claim
2 words
Methyl 14-phenyl-11α,15S-dihydroxy-9-oxoprost-13E-en-1-oate.
Claim 16
Dependent Claim
2 words
14-Phenyl-11α,15S-dihydroxy-9-oxoprost-13E-en-1-oic acid.
Claim 17
Dependent Claim
2 words
14-Phenyl-11α,15S-dihydroxy-9-oxoprost-13E-en-1-oic acid.
Claim 18
Dependent Claim
2 words
14-Phenyl-11α,15R-dihydroxy-9-oxoprost-13E-en-1-oic acid.
Claim 19
Dependent Claim
2 words
14-Phenyl-11α,15R-dihydroxy-9-oxoprost-13E-en-1-oic acid.
Claim 20
Dependent Claim
2 words
Methyl 5,6,17,18,19,20-hexanor-4,7-inter-o-phenylene-14-phenyl-15S-hydroxy-9-oxo-ent-prost-13E-en-1-oate.
Claim 21
Dependent Claim
2 words
Methyl 5,6,17,18,19,20-hexanor-4,7-inter-o-phenylene-14-phenyl-15S-hydroxy-9-oxo-ent-prost-13E-en-1-oate.
Claim 22
Dependent Claim
2 words
Methyl dl-14-phenyl-15R,S-hydroxy-9-oxoprost-13E-en-1-oate.
Claim 23
Dependent Claim
2 words
Methyl dl-14-phenyl-15R,S-hydroxy-9-oxoprost-13E-en-1-oate.
Claim 24
Dependent Claim
3 words
Methyl dl-14-phenyl-15R,S-hydroxy-9-oxoprost-13E-en-1-oic acid.
Claim 25
Dependent Claim
3 words
Methyl dl-14-phenyl-15R,S-hydroxy-9-oxoprost-13E-en-1-oic acid.
Claim 26
Dependent Claim
2 words
Ethyl 14-Phenyl-11α,15R-dihydroxy-9-oxoprosta-5Z,13E-dien-1-oate.
Claim 27
Dependent Claim
2 words
Ethyl 14-Phenyl-11α,15R-dihydroxy-9-oxoprosta-5Z,13E-dien-1-oate.
Claim 28
Dependent Claim
1 words
Ethyl-14-Phenyl-11α,15S-dihydroxy-9-oxoprosta-5Z,13E-dien-1-oate.
Claim 29
Dependent Claim
1 words
Ethyl-14-Phenyl-11α,15S-dihydroxy-9-oxoprosta-5Z,13E-dien-1-oate.
Claim 30
Dependent Claim
2 words
Methyl dl-14-phenyl-15R-hydroxy-9-oxoprosta-5,13E-dien-1-oate.
Claim 31
Dependent Claim
2 words
Methyl dl-14-phenyl-15R-hydroxy-9-oxoprosta-5,13E-dien-1-oate.
Claim 32
Dependent Claim
2 words
Methyl dl-14-phenyl-15S-hydroxy-9-oxoprosta-5Z,13E-dien-1-oate.
Claim 33
Dependent Claim
2 words
Methyl dl-14-phenyl-15S-hydroxy-9-oxoprosta-5Z,13E-dien-1-oate.
Claim 34
Dependent Claim
2 words
dl-14-Phenyl-15S-hydroxy-9-oxoprosta-5Z,13E-dien-1-oic acid.
Claim 35
Dependent Claim
2 words
dl-14-Phenyl-15S-hydroxy-9-oxoprosta-5Z,13E-dien-1-oic acid.
Claim 36
Dependent Claim
2 words
dl-14-Phenyl-15R-hydroxy-9-oxoprosta-5Z-13E-dien-1-oic acid.
Claim 37
Dependent Claim
2 words
dl-14-Phenyl-15R-hydroxy-9-oxoprosta-5Z-13E-dien-1-oic acid.
Claim 38
Dependent Claim
2 words
14-Phenyl-15R-hydroxy-9-oxo-ent-prosta-10,13E-dien-1-oic acid.
Claim 39
Dependent Claim
2 words
14-Phenyl-15R-hydroxy-9-oxo-ent-prosta-10,13E-dien-1-oic acid.
Claim 40
Dependent Claim
2 words
14-Phenyl-15S-hydroxy-9-oxoprosta-10,13E-dien-1-oic acid.
Claim 41
Dependent Claim
2 words
14-Phenyl-15S-hydroxy-9-oxoprosta-10,13E-dien-1-oic acid.
Claim 42
Dependent Claim
2 words
14-Phenyl-7α,11α,15R,S-trihydroxyprosta-5Z,13E-dien-1-oic acid.
Claim 43
Dependent Claim
2 words
14-Phenyl-7α,11α,15R,S-trihydroxyprosta-5Z,13E-dien-1-oic acid.
Claim 44
Dependent Claim
128 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregation amount of a compound having the formula: ##STR59## wherein: J is selected from the group consisting of methylene, R-hydroxymethylene, S-hydroxymethylene and methine; L is selected from the group consisting of methylene and methine with the proviso that L is methine only when J is methine: M is selected from the group consisting of carbonyl, R-hydroxymethylene, S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 45
Dependent Claim
128 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregation amount of a compound having the formula: ##STR59## wherein: J is selected from the group consisting of methylene, R-hydroxymethylene, S-hydroxymethylene and methine; L is selected from the group consisting of methylene and methine with the proviso that L is methine only when J is methine: M is selected from the group consisting of carbonyl, R-hydroxymethylene, S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 46
Dependent Claim
94 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregating amount of a compound having the formula: ##STR60## wherein: J is selected from the group consisting of methylene and R-hydroxymethylene or S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 47
Dependent Claim
94 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregating amount of a compound having the formula: ##STR60## wherein: J is selected from the group consisting of methylene and R-hydroxymethylene or S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 48
Dependent Claim
72 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregating amount of a compound having the formula: ##STR61## wherein: Q is ethylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 49
Dependent Claim
72 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregating amount of a compound having the formula: ##STR61## wherein: Q is ethylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 50
Dependent Claim
69 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregating amount of a compound having the formula: ##STR62## wherein: T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable nontoxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 51
Dependent Claim
69 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregating amount of a compound having the formula: ##STR62## wherein: T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable nontoxic salts; and B is a loweralkyl having from 1 to 5 carbon atoms.
Claim 52
Dependent Claim
29 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregating amount of methyl 14-phenyl-11α,15S-dihydroxy-9-oxoprost-13E-en-1-oate.
Claim 53
Dependent Claim
29 words
A therapeutic method for inhibiting platelet aggregation in an individual for whom such therapy is indicated, comprising: administering to the individual an effective platelet aggregating amount of methyl 14-phenyl-11α,15S-dihydroxy-9-oxoprost-13E-en-1-oate.
Claim 54
Dependent Claim
38 words
A therapeutic method of inhibiting the smooth muscle stimulant response to PGE 1 and PGF 2 α in an individual for whom such therapy is indicated, comprising: administering to the individual an effective inhibiting amount of methyl 14-phenyl-11α,15S-dihydroxy-9-oxoprost-13E-en-1-oate.
Claim 55
Dependent Claim
38 words
A therapeutic method of inhibiting the smooth muscle stimulant response to PGE 1 and PGF 2 α in an individual for whom such therapy is indicated, comprising: administering to the individual an effective inhibiting amount of methyl 14-phenyl-11α,15S-dihydroxy-9-oxoprost-13E-en-1-oate.
Claim 56
Independent Claim
346 words
A method for preparing a compound of the formula ##STR63## wherein: J is selected from the group consisting of methylene, R-hydroxymethylene, S-hydroxymethylene and methine; L is selected from the group consisting of methylene or methine, with the proviso that L is methine only when J is methine; M is selected from the group consisting of carbonyl, R-hydroxymethylene, and S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic cations; and B is a loweralkyl of from 1 to 5 carbon atoms; comprising: (a) reacting an organolithiocuprate having the formula, ##STR64## wherein: Lig is selected from the group consisting of tri-(di-alkylamino) phosphine of 6-12 carbon atoms, trialkylphosphine having 3-13 carbon atoms, diarylphosphine, dialkylsulfide having 4-8 carbon atoms, arylsulfide, and di-(trialkylsilyl) amino having 6-12 carbon atoms; R r is selected from the group consisting of iodide, thiophenylate and alkyn-1-yl having 3-8 carbon atoms; X is an integer of the set 1 to 2; R t is a radical having the formula, ##STR65## with a 2-cyclopenten-1-one having the formula, ##STR66## wherein: T' is selected from the group consisting of an alkoxycrbonyl having from 2 to 3 carbon atoms inclusive, and --CH 2 OA; wherein: A is selected from the group consisting of tetrahydropyran-2-yl, trialkylsilyl, triarylsilyl, alkoxyalkyl having 2-6 carbon atoms, or a triarylmethyl group; in an inert solvent, under inert atmosphere, at a temperature of from about -80° C. to about +10° C. for about 0.25 to about 3 hours to form a first intermediate having the formula, ##STR67## (b) reacting the first intermediate with a weak acid to obtain a first compound having the formula, ##STR68## (c) when T is alkoxycarbonyl, hydrolyzing the first compound to obtain a second compound having the formula, ##STR69## (d) when J is R-hydroxymethylene or S-hydroxymethylene, reducing the first compound to obtain a third compound having the formula, ##STR70## (e) when J is R-hydroxymethylene or S-hydroxymethylene, dehydrating the first compound, to obtain said compound having the formula, ##STR71##
Claim 57
Independent Claim
346 words
A method for preparing a compound of the formula ##STR63## wherein: J is selected from the group consisting of methylene, R-hydroxymethylene, S-hydroxymethylene and methine; L is selected from the group consisting of methylene or methine, with the proviso that L is methine only when J is methine; M is selected from the group consisting of carbonyl, R-hydroxymethylene, and S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable non-toxic cations; and B is a loweralkyl of from 1 to 5 carbon atoms; comprising: (a) reacting an organolithiocuprate having the formula, ##STR64## wherein: Lig is selected from the group consisting of tri-(di-alkylamino) phosphine of 6-12 carbon atoms, trialkylphosphine having 3-13 carbon atoms, diarylphosphine, dialkylsulfide having 4-8 carbon atoms, arylsulfide, and di-(trialkylsilyl) amino having 6-12 carbon atoms; R r is selected from the group consisting of iodide, thiophenylate and alkyn-1-yl having 3-8 carbon atoms; X is an integer of the set 1 to 2; R t is a radical having the formula, ##STR65## with a 2-cyclopenten-1-one having the formula, ##STR66## wherein: T' is selected from the group consisting of an alkoxycrbonyl having from 2 to 3 carbon atoms inclusive, and --CH 2 OA; wherein: A is selected from the group consisting of tetrahydropyran-2-yl, trialkylsilyl, triarylsilyl, alkoxyalkyl having 2-6 carbon atoms, or a triarylmethyl group; in an inert solvent, under inert atmosphere, at a temperature of from about -80° C. to about +10° C. for about 0.25 to about 3 hours to form a first intermediate having the formula, ##STR67## (b) reacting the first intermediate with a weak acid to obtain a first compound having the formula, ##STR68## (c) when T is alkoxycarbonyl, hydrolyzing the first compound to obtain a second compound having the formula, ##STR69## (d) when J is R-hydroxymethylene or S-hydroxymethylene, reducing the first compound to obtain a third compound having the formula, ##STR70## (e) when J is R-hydroxymethylene or S-hydroxymethylene, dehydrating the first compound, to obtain said compound having the formula, ##STR71##
Claim 58
Independent Claim
279 words
A method for preparing a compound having the formula, ##STR72## wherein: J is selected from the group consisting of methylene and R-hydroxymethylene or S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable nontoxic cations; and B is a loweralkyl having from 1 to 5 carbon atoms; comprising: (a) reacting an organolithiocuprate having the formula, ##STR73## wherein: Lig is selected from the group consisting of tri-(di-alkylamino) phosphine of 6-12 carbon atoms, trialkylphosphine having 3-13 carbon atoms, diarylphosphine, dialkylsulfide having 4-8 carbon atoms, arylsulfide, and di-(trialkylsilyl) amino havng 6-12 carbon atoms; R r is selected from the group consisting of iodide, thiophenylate and alkyn-1-yl having 3-8 carbon atoms; X is an integer of the set 1 to 2; R t is a radical having the formula ##STR74## with a 2-cyclopenten-1-one having the formula, ##STR75## wherein: T' is selected from the group consisting of an alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, and --CH 2 OA; wherein: A is selected from the group consisting of tetrahydropyran-2-yl, trialkylsilyl, triarylsilyl, alkoxyalkyl having 2-6 carbon atoms, or a triarymethyl group, in an inert solvent, under inert atmosphere, at a temperature of from about -80° C. to about +10° C. for about 0.25 to about 3 hours to form a first intermediate having the formula, ##STR76## (b) reacting the first intermediate with a weak acid to obtain a first compound having the formula, wherein T is alkoxycarbonyl having from 7 to 3 carbon atoms inclusive, ##STR77## (c) hydrolyzing the first compound to obtain said compound having the formula, ##STR78##
Claim 59
Independent Claim
279 words
A method for preparing a compound having the formula, ##STR72## wherein: J is selected from the group consisting of methylene and R-hydroxymethylene or S-hydroxymethylene; Q is selected from the group consisting of ethylene, Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable nontoxic cations; and B is a loweralkyl having from 1 to 5 carbon atoms; comprising: (a) reacting an organolithiocuprate having the formula, ##STR73## wherein: Lig is selected from the group consisting of tri-(di-alkylamino) phosphine of 6-12 carbon atoms, trialkylphosphine having 3-13 carbon atoms, diarylphosphine, dialkylsulfide having 4-8 carbon atoms, arylsulfide, and di-(trialkylsilyl) amino havng 6-12 carbon atoms; R r is selected from the group consisting of iodide, thiophenylate and alkyn-1-yl having 3-8 carbon atoms; X is an integer of the set 1 to 2; R t is a radical having the formula ##STR74## with a 2-cyclopenten-1-one having the formula, ##STR75## wherein: T' is selected from the group consisting of an alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, and --CH 2 OA; wherein: A is selected from the group consisting of tetrahydropyran-2-yl, trialkylsilyl, triarylsilyl, alkoxyalkyl having 2-6 carbon atoms, or a triarymethyl group, in an inert solvent, under inert atmosphere, at a temperature of from about -80° C. to about +10° C. for about 0.25 to about 3 hours to form a first intermediate having the formula, ##STR76## (b) reacting the first intermediate with a weak acid to obtain a first compound having the formula, wherein T is alkoxycarbonyl having from 7 to 3 carbon atoms inclusive, ##STR77## (c) hydrolyzing the first compound to obtain said compound having the formula, ##STR78##
Claim 60
Independent Claim
254 words
A method for preparing a compound having the formula, ##STR79## wherein: Q ia Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable nontoxic cations; and B is a loweralkyl having from 1 to 5 carbon atoms; comprising: (a) reacting an organolithiocuprate having the formula, ##STR80## wherein: Lig is selected from the group consisting of tri-(di-alkylamino) phosphine of 6-12 carbon atoms, trialkylphosphine having 3-13 carbon atoms, diarylphosphine, dialkylsulfide having 4-8 carbon atoms, arylsulfide, and di-(trialkylsilyl) amino having 6-12 carbon atoms; R r is selected from the group consisting of iodide, thiophenylate and alkyn-1-yl having 3-8 carbon atoms; X is an integer of the set 1 to 2; R t is a radical having the formula ##STR81## with a 2-cyclopenten-1-one having the formula, ##STR82## wherein: T' is selected from the group consisting of an alkoxycarbonyl having from 2 to 3 carbon atoms, inclusive, and --CH 2 OA; wherein: A is selected from the group consisting of tetrahydropyran-2-yl, trialkylsilyl, triarylsilyl, alkoxyalkyl having a 2-6 carbon atoms, or a triarymethyl group; in an inert solvent, under inert atmosphere, at a temperature of from about -80° C. to about +10° C. for about 0.25 to about 3 hours to form a first intermediate having the formula, ##STR83## (b) reacting the first intermediate with a weak acid to obtain a first compound having the formula, wherein J is R-hydroxymethylene or S-hydroxymethylene; ##STR84## (c) dehydrating the first compound to obtain said compound having the formula, ##STR85##
Claim 61
Independent Claim
254 words
A method for preparing a compound having the formula, ##STR79## wherein: Q ia Z-vinylene and inter-phenylene; T is selected from the group consisting of alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable nontoxic cations; and B is a loweralkyl having from 1 to 5 carbon atoms; comprising: (a) reacting an organolithiocuprate having the formula, ##STR80## wherein: Lig is selected from the group consisting of tri-(di-alkylamino) phosphine of 6-12 carbon atoms, trialkylphosphine having 3-13 carbon atoms, diarylphosphine, dialkylsulfide having 4-8 carbon atoms, arylsulfide, and di-(trialkylsilyl) amino having 6-12 carbon atoms; R r is selected from the group consisting of iodide, thiophenylate and alkyn-1-yl having 3-8 carbon atoms; X is an integer of the set 1 to 2; R t is a radical having the formula ##STR81## with a 2-cyclopenten-1-one having the formula, ##STR82## wherein: T' is selected from the group consisting of an alkoxycarbonyl having from 2 to 3 carbon atoms, inclusive, and --CH 2 OA; wherein: A is selected from the group consisting of tetrahydropyran-2-yl, trialkylsilyl, triarylsilyl, alkoxyalkyl having a 2-6 carbon atoms, or a triarymethyl group; in an inert solvent, under inert atmosphere, at a temperature of from about -80° C. to about +10° C. for about 0.25 to about 3 hours to form a first intermediate having the formula, ##STR83## (b) reacting the first intermediate with a weak acid to obtain a first compound having the formula, wherein J is R-hydroxymethylene or S-hydroxymethylene; ##STR84## (c) dehydrating the first compound to obtain said compound having the formula, ##STR85##
Claim 62
Independent Claim
248 words
A method for preparing a compound having the formula, ##STR86## wherein: T is selected from the group consisting of alkoyxcarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable nontoxic cations; and B is loweralkyl having from 1 to 5 carbon atoms; comprising: (a) reacting an organolithiocuprate having the formula, ##STR87## wherein: Lig is selected from the group consisting of tri-(di-alkylamino) phosphine of 6-12 carbon atoms, trialkylphosphine having 3-13 carbon atoms, diarylphosphine, dialkylsulfide having 4-8 carbon atoms, arylsulfide, and di-(trialkylsilyl) amino having 6-12 carbon atoms; R r is selected from the group consisting of iodide, thiophenylate and alkyn-1-yl having 3-8 carbon atoms; X is an integer of the set 1 to 2; R t is a radical having the formula ##STR88## with a 2-cyclopenten-1-one having the formula, ##STR89## wherein: T' is selected from the group consisting of an alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, and --CH 2 OA; wherein: A is selected from the group consisting of tetrahydropyran-2-yl, trialkylsilyl, triarylsilyl, alkoxyalkyl having a 2-6 carbon atoms, or a triarymethyl group; in an inert solvent, under inert atmosphere, at a temperature of from about -80° C. to about +10° C. for about 0.25 to about 3 hours to form a first intermediate having the formula, ##STR90## (b) reacting the first intermediate with a weak acid to obtain a first compound having the formula, wherein J is R-hydroxymethylene or S-hydroxymethylene, ##STR91## (c) reducing the first compound to obtain said compound having the formula, ##STR92##
Claim 63
Independent Claim
248 words
A method for preparing a compound having the formula, ##STR86## wherein: T is selected from the group consisting of alkoyxcarbonyl having from 2 to 3 carbon atoms inclusive, carboxyl and pharmacologically acceptable nontoxic cations; and B is loweralkyl having from 1 to 5 carbon atoms; comprising: (a) reacting an organolithiocuprate having the formula, ##STR87## wherein: Lig is selected from the group consisting of tri-(di-alkylamino) phosphine of 6-12 carbon atoms, trialkylphosphine having 3-13 carbon atoms, diarylphosphine, dialkylsulfide having 4-8 carbon atoms, arylsulfide, and di-(trialkylsilyl) amino having 6-12 carbon atoms; R r is selected from the group consisting of iodide, thiophenylate and alkyn-1-yl having 3-8 carbon atoms; X is an integer of the set 1 to 2; R t is a radical having the formula ##STR88## with a 2-cyclopenten-1-one having the formula, ##STR89## wherein: T' is selected from the group consisting of an alkoxycarbonyl having from 2 to 3 carbon atoms inclusive, and --CH 2 OA; wherein: A is selected from the group consisting of tetrahydropyran-2-yl, trialkylsilyl, triarylsilyl, alkoxyalkyl having a 2-6 carbon atoms, or a triarymethyl group; in an inert solvent, under inert atmosphere, at a temperature of from about -80° C. to about +10° C. for about 0.25 to about 3 hours to form a first intermediate having the formula, ##STR90## (b) reacting the first intermediate with a weak acid to obtain a first compound having the formula, wherein J is R-hydroxymethylene or S-hydroxymethylene, ##STR91## (c) reducing the first compound to obtain said compound having the formula, ##STR92##
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