US4089855A
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Process for the stereoselective reduction of 6- and 8-keto morphine and morphinan derivatives with formamidinesulfinic acid and compounds obtained thereby
Assignee: Cornell Research Foundation Inc
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Filing: 1976-04-23
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Granted: 1978-05-16
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Expires: 1996-04-23
Abstract
Abstract Process for the stereoselective synthesis of 6β-and 8β- hydroxy epimers by the chemical reduction of 6- and 8-keto derivatives in the morphine and morphinan series utilizing alkaline formamidinesulficic acid. The 6β- and 8β-hydroxy derivatives obtained according to the invention evidence narcotic antagonist and/or agonist activity and are also useful in the chemical and pharmacological standardization of various morphine and codeine derivatives and metabolites.
Inventors
- 👤 Nithiananda Chatterjie
- 👤 Charles E. Inturrisi
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 12:21
CPC Classifications
C; C07; C07D; C07D221/00; C07D221/02; C07D221/22; C07D221/28; C07D489/00; C07D489/02; C07D489/06; C07D489/08
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
40 words
Process for the stereoselective reduction of of 6- or 8-keto-6,7-dihydromorphine and 6- or 8-keto morphinan derivatives to form the corresponding 6β-hydroxy or 8β-hydroxy epimers thereof which comprises reducing said 6-keto or 8-keto derivatives with an alkaline solution of formamidinesulfinic acid.
Claim 2
Dependent Claim
40 words
Process for the stereoselective reduction of of 6- or 8-keto-6,7-dihydromorphine and 6- or 8-keto morphinan derivatives to form the corresponding 6β-hydroxy or 8β-hydroxy epimers thereof which comprises reducing said 6-keto or 8-keto derivatives with an alkaline solution of formamidinesulfinic acid.
Claim 3
Dependent Claim
17 words
The process of claim 1, wherein the solvent of said alkaline solution of formamidinesulfinic acid comprises water.
Claim 4
Dependent Claim
20 words
The process of claim 1, wherein said alkaline solution of formamidinesulfinic acid comprises said acid in an aqueous-ethanol solvent mixture.
Claim 5
Dependent Claim
16 words
The process of claim 1, wherein said process is carried out in an inert nitrogen atmosphere.
Claim 6
Dependent Claim
97 words
The process of claim 1, wherein said 6- or 8-keto derivatives have the formula: ##STR26## or the formula: ##STR27## wherein R 1 is selected from hydrogen, lower alkyl, lower alkenyl, lower alkynyl, carbocyclic lower alkyl, lower alkyl ring-substituted carbocyclic lower alkyl, cycloalkenyl, cycloalkenyl lower alkyl, furyl lower alkyl, thiophenyl lower alkyl, pyridinyl lower alkyl, piperidinyl lower alkyl, and thiozolyl lower alkyl; R 2 and R 3 is selected from hydrogen and ═O, and ═O and hydrogen, respectively; R 4 is selected from hydroxy, and lower alkoxy; and R 5 is selected from hydrogen, hydroxy and lower acyl.
Claim 7
Dependent Claim
45 words
The process of claim 5, wherein R 1 is selected from hydrogen, lower alkyl, ##STR28## where X is hydrogen or methyl; R 2 and R 3 are selected from hydrogen and ═O, and ═O and hydrogen, respectively; R 5 is selected from hydrogen and hydroxyl.
Claim 8
Dependent Claim
43 words
The process of claim 6, wherein R 1 is selected from hydrogen, lower alkyl, ##STR29## in which X is H or CH 3 , R 4 is selected from OH and OCH.sub.3, and R 5 is selected from H, OH and (lower) acyl.
Claim 9
Dependent Claim
30 words
The process of claim 7, wherein R 1 is selected from hydrogen, lower alkyl, ##STR30## R 4 is OH or OCH 3 , and R 5 is H or OH.
Claim 10
Dependent Claim
21 words
The process of claim 8, wherein R 4 is OH, R 1 is ##STR31## and R 5 is H or OH.
Claim 11
Dependent Claim
22 words
The process of claim 8, wherein R 4 is OH and R 1 is ##STR32## and R 5 is H or OH.
Claim 12
Dependent Claim
11 words
The process of claim 5, wherein a 6-keto derivative is reduced.
Claim 13
Dependent Claim
11 words
The process of claim 5, wherein an 8-keto derivative is reduced.
Claim 14
Dependent Claim
12 words
The process of claim 11, wherein a 6-keto morphine derivative is reduced.
Claim 15
Dependent Claim
17 words
The process of claim 13, wherein said derivative is selected from the group 17-cyclobutylmethyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one, 17-methyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one, 17-methyl-4,5α-epoxy-3-hydroxymorphinan-6-one, 17-methyl-4,5α-epoxy-3-methoxymorphinan-6-one.
Claim 16
Dependent Claim
11 words
The process of claim 12, wherein said derivative is dihydropseudo codeinone.
Claim 17
Dependent Claim
12 words
The process of claim 11, wherein a 6-keto morphinan derivative is reduced.
Claim 18
Dependent Claim
14 words
The process of claim 16, wherein said derivative is selected from 17-cyclobutylmethyl-3,14-dihydroxymorphinan-6-one and 17-cyclobutylmethyl-3-methoxy-14-hydroxymorphinan-6-one.
Claim 19
Dependent Claim
36 words
A compound of the formula: ##STR33## wherein: R 3 represents β-hydroxy, lower alkoxy containing 1 to 6 carbon atoms or lower alkanoyloxy containing 2 to 6 carbon atoms, or a pharmaceutically acceptable acid addition salt thereof.
Claim 20
Dependent Claim
36 words
A compound of the formula: ##STR33## wherein: R 3 represents β-hydroxy, lower alkoxy containing 1 to 6 carbon atoms or lower alkanoyloxy containing 2 to 6 carbon atoms, or a pharmaceutically acceptable acid addition salt thereof.
References Cited (Backward Citations)
US2774762A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-05-15 | 1981-11-14 | 1982-05-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-05-15 | 1985-11-14 | 1986-05-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-05-15 | 1989-11-14 | 1990-05-16 | $7700.00 | Window Closed / Lapsed |