FI92602C - Förfarande för framställning av -2',3'-dideoxiinosin genom enzymatiks deaminering - Google Patents
Förfarande för framställning av -2',3'-dideoxiinosin genom enzymatiks deaminering Download PDFInfo
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- FI92602C FI92602C FI883339A FI883339A FI92602C FI 92602 C FI92602 C FI 92602C FI 883339 A FI883339 A FI 883339A FI 883339 A FI883339 A FI 883339A FI 92602 C FI92602 C FI 92602C
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- protecting group
- hydroxy protecting
- compound
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- 238000000034 method Methods 0.000 title claims description 25
- 238000002360 preparation method Methods 0.000 title claims description 8
- 230000009615 deamination Effects 0.000 title description 4
- 238000006481 deamination reaction Methods 0.000 title description 4
- 230000002255 enzymatic effect Effects 0.000 title description 3
- 125000006239 protecting group Chemical group 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 17
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine group Chemical group [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C=NC=2C(N)=NC=NC12 OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 15
- 102000055025 Adenosine deaminases Human genes 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 12
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 claims description 10
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- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 7
- 229960005305 adenosine Drugs 0.000 claims description 7
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- 229910052794 bromium Inorganic materials 0.000 claims description 4
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- 239000010936 titanium Substances 0.000 description 1
- 125000005106 triarylsilyl group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/38—Nucleosides
- C12P19/40—Nucleosides having a condensed ring system containing a six-membered ring having two nitrogen atoms in the same ring, e.g. purine nucleosides
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (11)
1. FOrfarande varmed selektivt framstailes β-2',3'-dideoxiinosin, med formeln A
2. FOrfarande enligt patentkrav 1, kSnne- t e c k n a t dSrav, att det vid stegen (a) och (b) an-vSnda reduktionsmediet ar BH3 (B2H6), BH3SMe2, [(CH3CHCH(CH3)]2BH, NaBH4, NaBH4 och antingen LiCl eller A1C13 eller BF3, LiAlH4, LiAlH( OMe )3 eller LiAlH( OBu-t )3.
3. FOrfarande enligt patentkrav 1, kånne- t e c k n a t darav, att det vid steget (b) anvSnda reduktionsmediet år [(CH3)2CHCH(CH3)]2BH.
4. FOrfarande enligt patentkrav 1, k a η n e -t e c k n a t dårav, att den vid steget (a) anvSnda hyd- 35 roxiskyddsgruppen Sr en bensoylgrupp. • 92602 21
5. F5rfarande enligt patentkrav 1, kanne-t e c k n a t darav, att mellanprodukten enligt steg (c) reagerar med (CH3)3SiBr som harvid fungerar som en forening med formeln MX.
5 O HN^Ti-N OQ N N (A) HOCH00 O kannetecknat darav, att det omfattar f01jånde steg: 15 a) man omvandlar en^-karboxi-^-butyrolakton med formeln B HOOC till en 5-O-hydroxiskyddsgrupp-metyl-^-butyrolakton med formeln C 25 RO—i ^ o T/' 30 vari R ar en hydroxiskyddsgrupp, genom att man bringar en forening med formeln B att reagera med ett karboxylgrupp-reducerande reagens och darefter bringar den erhållna hyd-roximetylgruppen att reagera med ett hydroxiskyddsgrupps-35 reagens; 92602 19 b) man omvandlar mellanprodukten från steg (a) med formeln C, till 5-0-hydroxiskyddsgrupp-metyl-2,3-dideoxi-pentofuranos med formeln D vari R år en hydroxiskyddsgrupp, genom att bringa en 10 forening med formeln C att reagera med ett karbony1grupp-reducerande reagens; c) man omvandlar mellanprodukten från steg (b) med formeln D, till en 1-O-aktiverande grupp-5-O-hydroxi-skyddsgrupp-metyl-2,3-dideoxipentofuranos med formeln E 15 RO-1 o vari R år en hydroxiskyddsgrupp och A år en O-aktiverande grupp, som år en alkylkarbonylgrupp, genom att bringa en fbrening med formeln D att reagera med ett acylerande åmne som motsvarar grupp A ovan; : 25 d) man omvandlar mellanprodukten från steg (c), en fttrening med formeln E, genom reaktion med en forening med formeln MX till 1-avgående grupp-5-0-hydroxiskyddsgrupp-metyl-2,3-dideoxipentofuranos med formeln F 30 ROno^x 35 vari R år en hydroxiskyddsgrupp och X år en avgående 20 92602 grupp, som Sr Cl eller Br, genom att bringa en forening med formeln E att reagera med en forening med formeln MX, var i M Sr en (CH3)3Si; e) man bringar mellanprodukten från steg (d) med 5 formeln F att reagera med ett aktiverat adeninderivat vari basen, adenin, Sr aktiverad genom att låta C-6-aminogrup-pen i ringen hos nSmnda bas och N-9 kvSvea tomen reager a med en aktiverande forening som Sr ett silylerande eller acylerande eller bensoylerande Smne, sålunda, att nårvar- 10 ånde Sr en BrOnstedsyra eller en Lewissyra och ett 10s-ningsmedel, som Sr ett polSrt eller ej polSrt lOsningsme-del; och f) man utfOr en kemisk reaktion med mellanprodukten från steg (e) som formår substituere 5-O-hydroxiskydds- 15 gruppen, varvid man erhåller en blandning av B- och a-2',3'-dideoxiadenosinanomerer; g) man bringar blandningen av β- och a-2',3’-dide-oxiadenosin från steg (f) i kontakt med enzymet adenosin-deaminas fOr att aminogruppen i adenosinringsystemet i 6- 20 stSllning skall substitueras selektivt hos B-2',3'-dideoxiadenosinet med en hydroxylgrupp, varvid adenosinet omvandlas till inosin; och h) man tager tillvara dideoxiinosinet från foregående steg (g).
6. FOrfarande enligt patentkrav 1, kanne- t e c k n a t darav, att vid steg (e) reagerar adenosin-basforeningen, aktiverad genom reaktion med en halotrial-kylsilan, varvid denna fungerar som silylerande amne, vari halo ar brom eller jod, reagerar med 1-avgående grupp-5-10 0-skyddsgrupp-2',3'-dideoxipentafuranosmellanprodukten med formeln F från steg (d), varvid man erhåller en 5*-0-hydroxi-skyddsgrupp-2',3,-dideoxiadenosinmellanprodukt.
7. FOrfarande enligt patentkrav 6, kanne- t e c k n a t darav, att reaktionssteg (e) utfOres i ett 15 ej polart lOsningsmedel ar CHC13, CH2C12, C1CH2-CH2C1 eller CC14.
8. FOrfarande enligt patentkrav 1, kanne- t e c k n a t darav, att reaktionerna vid stegen (d) och (e) utfOres i ett karl genom successiv tillsattning av ha-20 logeneringsmedel och aktiverat adenosinderivat till mellanprodukten från steg (c).
9. FOrfarande enligt patentkrav 8, kanne- t e c k n a t darav, att halogeneringsmedlet ar bromtri-metylsilan och det aktiverade adenosinderivatet ar bis-• 25 silyladenin.
10. FOrfarande enligt patentkrav 1, kanne- t e c k n a t darav, att mellanprodukten vid steg (f) reagerar mellanprodukten från steg (e), vari skyddsgruppen ar bensoyl, med ammoniakmattad metanol, varvid 5-0-hyd-30 roxiskyddsgruppen substitueres.
11. FOrfarande enligt patentkrav 1, kanne- t e c k n a t darav, att vid steg (g) anvandes enzymet, adenosindeaminas i form av en losning i ett neutralt vat-tenhaltigt medium eller i form av ett immobiliserat enzym- 35 preparat. «
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7484487A | 1987-07-17 | 1987-07-17 | |
| US7484487 | 1987-07-17 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI883339A0 FI883339A0 (sv) | 1988-07-13 |
| FI883339A7 FI883339A7 (sv) | 1989-01-18 |
| FI92602B FI92602B (sv) | 1994-08-31 |
| FI92602C true FI92602C (sv) | 1994-12-12 |
Family
ID=22122017
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI883339A FI92602C (sv) | 1987-07-17 | 1988-07-13 | Förfarande för framställning av -2',3'-dideoxiinosin genom enzymatiks deaminering |
Country Status (8)
| Country | Link |
|---|---|
| KR (1) | KR930005870B1 (sv) |
| AT (1) | AT395977B (sv) |
| CA (1) | CA1335187C (sv) |
| ES (1) | ES2007532A6 (sv) |
| FI (1) | FI92602C (sv) |
| GR (1) | GR1000483B (sv) |
| LU (1) | LU87280A1 (sv) |
| PT (1) | PT88017B (sv) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR861255B (en) * | 1985-05-15 | 1986-09-16 | Wellcome Found | Therapeutic nucleosides |
| EP0285884A3 (en) * | 1987-03-20 | 1990-07-04 | Bristol-Myers Squibb Company | process to produce 2', 3'-dideoxynucleosides |
-
1988
- 1988-07-04 AT AT0173088A patent/AT395977B/de not_active IP Right Cessation
- 1988-07-08 GR GR880100455A patent/GR1000483B/el not_active IP Right Cessation
- 1988-07-13 FI FI883339A patent/FI92602C/sv active IP Right Grant
- 1988-07-15 KR KR1019880008865A patent/KR930005870B1/ko not_active Expired - Lifetime
- 1988-07-15 LU LU87280A patent/LU87280A1/fr unknown
- 1988-07-15 PT PT88017A patent/PT88017B/pt not_active IP Right Cessation
- 1988-07-15 CA CA000572184A patent/CA1335187C/en not_active Expired - Lifetime
- 1988-07-15 ES ES8802250A patent/ES2007532A6/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| PT88017B (pt) | 1995-03-01 |
| KR930005870B1 (ko) | 1993-06-25 |
| ES2007532A6 (es) | 1989-06-16 |
| FI883339A7 (sv) | 1989-01-18 |
| FI883339A0 (sv) | 1988-07-13 |
| AT395977B (de) | 1993-04-26 |
| GR1000483B (el) | 1992-07-30 |
| CA1335187C (en) | 1995-04-11 |
| ATA173088A (de) | 1992-09-15 |
| LU87280A1 (fr) | 1989-03-08 |
| KR900001858A (ko) | 1990-02-27 |
| PT88017A (pt) | 1989-06-30 |
| GR880100455A (en) | 1989-04-12 |
| FI92602B (sv) | 1994-08-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BB | Publication of examined application | ||
| FG | Patent granted |
Owner name: BRISTOL-MYERS SQUIBB COMPANY |