GB1560903A - Intermediates for the preparation of 15 - deutro - protaglandins - Google Patents
Intermediates for the preparation of 15 - deutro - protaglandins Download PDFInfo
- Publication number
- GB1560903A GB1560903A GB4324/79A GB432479A GB1560903A GB 1560903 A GB1560903 A GB 1560903A GB 4324/79 A GB4324/79 A GB 4324/79A GB 432479 A GB432479 A GB 432479A GB 1560903 A GB1560903 A GB 1560903A
- Authority
- GB
- United Kingdom
- Prior art keywords
- deutero
- acetic acid
- lactone
- octenyl
- trans
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
- C07D307/937—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans with hydrocarbon or substituted hydrocarbon radicals directly attached in position 2, e.g. prostacyclins
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
PATENT SPECIFICATION
( 21) Application No 4324/79 ( 62) Divided out of No 1560 ( 31) Convention Application ( 32) Filed 25 June 1975 in ( 22) Filed 22 June 1976 902 No 8250/75 ( 11) 1 560 903 ( 19) ( 33) ( 44) ( 51) Switzerland (CH),
Complete Specification published 13 Feb 1980
INT CL 3 C 07 D 307/93 ( 52) Index at acceptance C 2 C 147 X 1672 200 213 215 220 226 22 Y 247 253 25 Y 28 X 300 Y 311 31 Y 351 352 360 362 364 366 368 36 Y 386 388 389 490 509 50 Y 623 624 625 628 633 634 652 662 668 672 67 X 694 699 761 767 AA TU ( 54) INTERMEDIATES FOR THE PREPARATION OF 15-DEUTERO-PROSTAGLANDINS ( 71) We, SANDOZ LTD, 35 Lichtstrasse, CH-4002 Basle, Switzerland, a Swiss body corporate, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:-
The present invention relates to intermediates for the preparation of 15 deuteroprostaglandins.
In accordance with the invention there are provided compounds of formula V, F -' V D OR 4 wherein C is a prostaglandin end group, F is F 2 F 1 0 9 o or OR 5 F 3 and R, and R, are, independently, hydrogen or an acid sensitive protecting group.
The compounds of formula V are, by virtue of the presence of the lactone group, useful as intermediates in one stage of the synthesis for the preparation of the compounds of formula I as described and claimed in our copending application No 25886/76, (Serial No 1,560,902) filed 22nd June, 1976.
The compounds for formula V can be obtained by deuterating a compound of formula VI, FIV 3, 0 wherein C is as defined above, and F' is Fl, F 2, F 3, as previously defined, or F 4 wherein R is hydrogen or a bulky group capable of influencing the proportion of a:, alcohol formed, and, if necessary, converting any group R 7 present into a group R, as previously defined, and if desired, protecting the 3-hydroxy group with an acid sensitive protecting group.
As indicated by the broken lines in formula VI, the 1 and 2 carbon atoms may be linked by a single bond or a trans double bond.
The reaction may be carried out in conventional manner for such deuterations bearing in mind the other groups present For example a deuterating agent such as sodium or zinc borodeuteride may be used An anhydrous inert organic solvent such as dimethyl formamide or dimethoxyethane may be present.
Suitable temperatures are between -40 and C Preferably the reaction is effected under an inert gas atmosphere.
The a and B/-alcohols which may both be formed may be separated in conventional manner.
The group R, may be chosen such that it influences by virtue of its size the proportion of a: i? alcohol formed generally increasing the amount of a-alcohol.
Such groups are well known in the art.
An example of a suitable protecting group R, is para-phenylbenzovl or benzoyl Such groups are split off under alkaline conditions, and may be exchanged for a group R in conventional manner.
The 3-hydroxy group may be protected in conventional manner.
4 M 2 L 560903 The compounds of formula VI can be obtained in accordance with known methods.
EXAMPLE 1 (-) -22 ( 3 ' deutero 3 'Y hydroxy4 ',4 ' dimethyl trans 1 ' octenyl)a hydroxy 3 a para phenyl benzoyloxy 1 l cyclopentyl acetic acid y lactone and (-) 2 ( 3 'deutero 3 '1 fhydroxy 4 ',4 ' dimethyl trans 1 ' octenyl) 5 ahydroxy 3 a para phenylbenzoyloxyla cyclopentyl acetic acid y-lactone (intermediate compounds of formula V' wherein the compounds of formula V possess a bulky group R 7 in the moiety F 4) A solution of 1 45 g of (-) 5 a hydroxy2,8 ( 3 'oxo 4 ',4 'dimethyl trans 1 'octenyl) 3 a para phenylbenzoyl oxyla cyclopentyl acetic acid y-lactone in 8 ml of absolute dimethoxyethane at -15 C in a nitrogen atmosphere Stirring is subsequently effected at 3 to 5 C for 3 5 hours and at to 10 C for one hour The mixture is then again cooled at -15 C and 3 ml of an aqueous 10 % (w/v) sodium hydrogen tartrate solution are slowly added The mixture is extracted with 2 x 100 ml of diethyl ether The organic phase is washed with 100 ml of a saturated aqueous sodium chloride solution, dried with sodium sulphate and concentrated by evaporation at reduced pressure, whereby a mixture of the corresponding a and j 3 isomers is obtained The residue is chromatographed on 50 g of neutral silica gel, whereupon the a and then the fl-isomer is eluted with chloroform ( 5 % ethyl acetate).
a-isomer:
Thin layer chromatography (Silica gel):
Methylene chloride ( 5 % acetic ester) Rf= 0 4, M Pt 107-108 C.
IR (methylene chloride) inter alia bands at: 3500, 1770, 1710, 1660 cm-.
/3-isomer:
Thin layer chromatography (Silica gel):
Methylene chloride ( 5 % acetic ester) Rf= O 3.
Spectral data approximately as for aisomer.
The following compounds of formula V can be prepared in manner analogous to that employed for the title compound of Example 1, using appropriate starting materials in approximately equivalent amounts:
2 2,8 ( 3 ' deutero 3 ',B hydroxy 4,4dimethyl trans 1 ' octenyl) 3 a,5 adihydroxy la cyclopentyl acetic acid r-lactone.
3. 2,B ( 3 'deutero 3 'a hydroxy trans1 ' octenyl) 3 a Sa dihydroxy lacyclopentyl acetic acid y lactone.
4. 24 ( 3 ' deutero 3 ',/ hydroxytrans 1 ' octenyl) 3 a,5 adihydroxyla cyclopentyl acetic acid y lactone.
5. 2/? ( 3 'deutero 3 'a hydroxy 4 ' 65 methyl trans 1 ' octenyl) 3 a,5 rdihydroxy la cyclopentyl acetic acid y lactone.
6. 243 ( 3 ' deutero 3 'Y hydroxy 4 'methyl trans 1 ' octenyl) 3 a,5 a 70 hydroxy la cyclopentyl acetic acid 3 y lactone.
7. 2 J ( 3 ' deutero 4,4 dimethyl 3 'ahydroxy trans 1 ' octenyl) a 5hydroxy la cyclopent 2 enyl acetic acid 75 y lactone.
8 2,B ( 4 N -butyl 3 ' deutero 3 'Shydroxy trans 1 ' octenyl) 3 a,5dihydroxy la cyclopentyl acetic acid y lactone 80 9 24 ( 4 N butyl 3 ' deutero 3 'Shydroxy trans 1 ' octenyl) 5 ahydroxy la cyclopent 3 enyl acetic acid y lactone.
2,8 ( 3 ' deutero 3 'R hydroxy 4 R 85 methyl trans 1 ' octenyl) 3 a,5 adihydroxy la cyclopentyl acetic acid y lactone.
11 24 ? ( 3 ' deutero 3 'R hydroxy 4 'methyl 4 ' l 3 " trifluoro methyl 90 phenoxyl trans 1 pentenyl) 3 a,5 adihydroxy la cyclopentyl acetic acid y lactone.
12 2/? ( 3 ' deutero 3 'S hydroxytrans 1 ' octenyl) 3 a,5, dihydroxy 95 la cyclopentyl acetic acid y lactone.
13 2/3 ( 3 'deutero 3 'S hydroxy trans1 ' octenyl) 5 a hydroxy 1 e cyclopent 3 enyl acetic acid y lactone.
14. 2 _ 8( 3 'deutero 3 'a hydroxy octyl) 100 a hydroxy la cyclo pentyl acetic acid y lactone.
15. 2/ ( 3 'deutero 3 'a hydroxy 4 '( 3 " trifluoromethyl phenoxy) trans1 butenyl) 3 a,5 a dihydroxy la 105 cyclo pentyl acetic acid y lactone.
Claims (1)
- WHAT WE CLAIM IS:-1 A compound of formula V, wherein C is a F is F 1 ' F 1 OR 4 prostaglandin end group, V F 2 F 3 obtained in (+) racemic form and in 3 'R or 3 'S optically active form The compounds of examples 5 and 6 may be obtained as the 4 'a-methyl isomer or the 4 'g-methyl isomer.1.560903 " 7 1,560,903 and RP and R 5 are, independently, hydrogen or an acid sensitive protecting group.2 (-) 2,/3 ( 3 'deutero 3 'a hydroxy4 ',4 ' dimethyl trans 1 ' octenyl) 5 ahydroxy 3 a para phenyl benzoyloxyla cyclopentyl acetic acid y lactone and (-) 2,5 ( 3 ' deutero 3 ',, hydroxy4 ',4 'dimethyl trans 1 ' octenyl) Sahydroxy 3 a paraphenylbenzoyloxy la cyclopentyl acetic acid y lactone.3 24 ? ( 3 'deutero 3 '1 hydroxy 4 ',4 'dimethyl trans 1 ' octenyl 3 a,5 a dihydroxy la cyclopentyl acetic acid ylactone.4 ZO ( 3 'deutero 3 'a hydroxy trans1 ' octenyl) 3 a,5 a dihydroxy la cydclopentyl acetic acid y lactone.2,83 ( 3 'deutero 3 'Y,hydroxy trans1 ' octenyl) 3 a,5 a dihydroxy l cyclopentyl acetic acid y lactone.6 2,5 ( 3 'deutero 3 'a hydroxy 4 'methyl trans 1 ' octenyl) 3 a,5 Sa dihydroxy la cyclopentyl acetic acid y lactone.7 25 ( 3 'deutero 3 ',B hydroxy 4 'methyl trans 1 ' octenyl) 3 a,5 a dihydroxy la cyclopentyl acetic acid y lactone.8 2,8 ( 3 ' deutero 4,4 dimethyl 3 'rahydroxy trans 1 ' octenyl) 5 a hydroxyla cyclopent 2 enyl acetic acid y lactone.9 23 ( 4 N butyl 3 ' deutero 3 'Shydroxy trans 1 ' octenyl) 3 a,5 dihydroxy la cyclopentyl acetic acid y lactone.2,3 ( 4 N butyl 3 ' deutero 3 'Shydroxy trans 1 ' octenyl) 5 a hydroxyla cyclopent 3 enyl acetic acid y lactone.11 2/3 ( 3 'deutero 3 'R hydroxy 4 Rmethyl trans 1 ' octenyl) 3 a,5 xt dihydroxy 1,a cyclopentyl acetic acid y lactone.12 2,, ( 3 'deutero 3 'R hydroxy 4 'methyl 4 ' l 3 " trifluoro methylphenoxyl trans 1 pentenyl) 3 a,5 a dihydroxy la cyclopentyl acetic acid y lactone.13 23 ( 3 ' deutero 3 'S hydroxytrans 1 ' octenyl) 3 a,5,a dihydroxy lcyclopentyl acetic acid y lactone.14 26 ( 3 ' deutero 3 'S hydroxytrans 1 ' octenyl) 5 a hydroxy lacyclopent 3 enyl acetic acid y lactone.2/3 ( 3 ' deutero 3 'a hydroxyoctyl) 5 a hydroxy la cyclo pentyl acetic acid y lactone.16 2,3 ( 3 'deutero 3 'a hydroxy 4 '( 3 " trifluoromethyl phenoxyl trans 1butenyl) 3 a Sa dihydroxy la cyclopentyl acetic acid y lactone.B A YORKE & CO, 98, The Centre, Feltham, Middx.Printed for Her Majesty's Stationery Office, by the Courier Press, Leamington Spa, 1980 Published by The Patent Office, 25 Southampton Buildings, London, WC 2 A l AY, from which copies may be obtained.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH825075 | 1975-06-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1560903A true GB1560903A (en) | 1980-02-13 |
Family
ID=4337463
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB4324/79A Expired GB1560903A (en) | 1975-06-25 | 1976-06-22 | Intermediates for the preparation of 15 - deutro - protaglandins |
| GB25886/76A Expired GB1560902A (en) | 1975-06-25 | 1976-06-22 | 15 - deutero-prostaglandin derivatives methods for their preparation and compositions containing said derivatives |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB25886/76A Expired GB1560902A (en) | 1975-06-25 | 1976-06-22 | 15 - deutero-prostaglandin derivatives methods for their preparation and compositions containing said derivatives |
Country Status (19)
| Country | Link |
|---|---|
| JP (1) | JPS523039A (en) |
| AT (1) | ATA460476A (en) |
| AU (1) | AU511527B2 (en) |
| BE (1) | BE843318A (en) |
| CA (1) | CA1095032A (en) |
| DD (1) | DD124727A5 (en) |
| DE (1) | DE2626582A1 (en) |
| DK (1) | DK270176A (en) |
| ES (1) | ES449147A1 (en) |
| FI (1) | FI761741A (en) |
| FR (2) | FR2316930A1 (en) |
| GB (2) | GB1560903A (en) |
| IL (1) | IL49889A (en) |
| NL (1) | NL7606709A (en) |
| NO (1) | NO762102L (en) |
| NZ (1) | NZ181264A (en) |
| PT (1) | PT65265B (en) |
| SE (1) | SE7606972L (en) |
| ZA (1) | ZA763810B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59161476U (en) * | 1983-04-14 | 1984-10-29 | 富士重工業株式会社 | Expansion valve control structure in refrigeration cycle |
-
1976
- 1976-06-14 DE DE19762626582 patent/DE2626582A1/en not_active Withdrawn
- 1976-06-16 FI FI761741A patent/FI761741A/fi not_active Application Discontinuation
- 1976-06-16 DK DK270176A patent/DK270176A/en unknown
- 1976-06-17 SE SE7606972A patent/SE7606972L/en unknown
- 1976-06-17 NO NO762102A patent/NO762102L/no unknown
- 1976-06-21 NL NL7606709A patent/NL7606709A/en not_active Application Discontinuation
- 1976-06-22 GB GB4324/79A patent/GB1560903A/en not_active Expired
- 1976-06-22 GB GB25886/76A patent/GB1560902A/en not_active Expired
- 1976-06-23 NZ NZ181264A patent/NZ181264A/en unknown
- 1976-06-23 ES ES449147A patent/ES449147A1/en not_active Expired
- 1976-06-23 CA CA255,572A patent/CA1095032A/en not_active Expired
- 1976-06-23 FR FR7619091A patent/FR2316930A1/en active Granted
- 1976-06-23 PT PT65265A patent/PT65265B/en unknown
- 1976-06-23 IL IL49889A patent/IL49889A/en unknown
- 1976-06-23 BE BE168237A patent/BE843318A/en unknown
- 1976-06-23 DD DD193532A patent/DD124727A5/xx unknown
- 1976-06-24 AT AT0460476A patent/ATA460476A/en not_active Application Discontinuation
- 1976-06-24 JP JP51073923A patent/JPS523039A/en active Pending
- 1976-06-25 AU AU15326/76A patent/AU511527B2/en not_active Expired
- 1976-06-25 ZA ZA00763810A patent/ZA763810B/en unknown
-
1977
- 1977-01-25 FR FR7701972A patent/FR2351974A1/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| PT65265A (en) | 1976-07-01 |
| IL49889A0 (en) | 1976-08-31 |
| GB1560902A (en) | 1980-02-13 |
| AU511527B2 (en) | 1980-08-21 |
| CA1095032A (en) | 1981-02-03 |
| IL49889A (en) | 1979-11-30 |
| FI761741A (en) | 1976-12-26 |
| ES449147A1 (en) | 1977-12-01 |
| FR2316930A1 (en) | 1977-02-04 |
| AU1532676A (en) | 1978-01-05 |
| FR2316930B1 (en) | 1978-11-17 |
| FR2351974A1 (en) | 1977-12-16 |
| PT65265B (en) | 1978-03-24 |
| SE7606972L (en) | 1976-12-26 |
| BE843318A (en) | 1976-12-23 |
| NO762102L (en) | 1976-12-28 |
| NL7606709A (en) | 1976-12-28 |
| NZ181264A (en) | 1978-07-10 |
| JPS523039A (en) | 1977-01-11 |
| FR2351974B1 (en) | 1980-08-14 |
| DE2626582A1 (en) | 1977-03-03 |
| ATA460476A (en) | 1982-01-15 |
| DD124727A5 (en) | 1977-03-09 |
| DK270176A (en) | 1976-12-26 |
| ZA763810B (en) | 1978-02-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |