CA1088927A - OBTENTION DE 5'-PHOSPHATE DE 9-(.beta.-D- ARABINOFURANOSYL)ADENINE - Google Patents

OBTENTION DE 5'-PHOSPHATE DE 9-(.beta.-D- ARABINOFURANOSYL)ADENINE

Info

Publication number: CA1088927A
Authority: CA; Canada
Prior art keywords: adenine; phosphate; arabinofuranosyl; product; mixture
Prior art date: 1976-11-03
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

Application number

CA342,182A

Other languages

English (en)

Inventor

Walter E. Behnke

Theodore H. Haskell

William R. Marsh

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Parke Davis and Co LLC

Original Assignee

Parke Davis and Co LLC

Priority date (The priority date 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 date listed.)

1976-11-03

Filing date

1979-12-18

Publication date

1980-11-04

1977-09-12 Priority claimed from US05/831,703 external-priority patent/US4123609A/en

1979-12-18 Application filed by Parke Davis and Co LLC filed Critical Parke Davis and Co LLC

1980-11-04 Application granted granted Critical

1980-11-04 Publication of CA1088927A publication Critical patent/CA1088927A/fr

Status Expired legal-status Critical Current

Links

229910019142 PO4 Inorganic materials 0.000 title claims abstract description 36
239000010452 phosphate Substances 0.000 title claims abstract description 36
238000000034 method Methods 0.000 title claims abstract description 21
238000004519 manufacturing process Methods 0.000 title claims abstract description 4
GFFGJBXGBJISGV-RVQWGROCSA-N 2,8-ditritio-7h-purin-6-amine Chemical compound [3H]C1=NC(N)=C2NC([3H])=NC2=N1 GFFGJBXGBJISGV-RVQWGROCSA-N 0.000 title 1
229960000643 adenine Drugs 0.000 claims abstract description 36
239000000047 product Substances 0.000 claims abstract description 35
229930024421 Adenine Natural products 0.000 claims abstract description 33
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims abstract description 33
239000000203 mixture Substances 0.000 claims abstract description 25
150000002148 esters Chemical class 0.000 claims abstract description 14
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 11
230000007062 hydrolysis Effects 0.000 claims abstract description 9
238000006460 hydrolysis reaction Methods 0.000 claims abstract description 9
239000011541 reaction mixture Substances 0.000 claims abstract description 9
239000002904 solvent Substances 0.000 claims abstract description 8
239000007787 solid Substances 0.000 claims abstract description 5
239000013067 intermediate product Substances 0.000 claims abstract 6
239000003085 diluting agent Substances 0.000 claims abstract 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical group ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 7
DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical group CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 claims description 6
230000000865 phosphorylative effect Effects 0.000 claims description 5
239000002244 precipitate Substances 0.000 claims description 4
230000026731 phosphorylation Effects 0.000 claims description 3
238000006366 phosphorylation reaction Methods 0.000 claims description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000000243 solution Substances 0.000 description 17
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
125000003317 D-arabinofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@@]([H])(O[H])[C@]1([H])O[H] 0.000 description 13
150000002500 ions Chemical class 0.000 description 10
239000002777 nucleoside Substances 0.000 description 10
150000003833 nucleoside derivatives Chemical class 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 6
239000001177 diphosphate Substances 0.000 description 6
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 6
235000011180 diphosphates Nutrition 0.000 description 6
238000003556 assay Methods 0.000 description 5
239000007791 liquid phase Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
239000005457 ice water Substances 0.000 description 3
238000005342 ion exchange Methods 0.000 description 3
238000010899 nucleation Methods 0.000 description 3
KUWPCJHYPSUOFW-UHFFFAOYSA-N 2-(hydroxymethyl)-6-(2-nitrophenoxy)oxane-3,4,5-triol Chemical compound OC1C(O)C(O)C(CO)OC1OC1=CC=CC=C1[N+]([O-])=O KUWPCJHYPSUOFW-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
-1 Phospho Chemical class 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
125000000328 arabinofuranosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
239000002002 slurry Substances 0.000 description 2
239000007790 solid phase Substances 0.000 description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
241000182988 Assa Species 0.000 description 1
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
229910019201 POBr3 Inorganic materials 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
241000700605 Viruses Species 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000002253 acid Substances 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000003957 anion exchange resin Substances 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000003518 caustics Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 1
125000003963 dichloro group Chemical group Cl* 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical class OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
238000010828 elution Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000000630 rising effect Effects 0.000 description 1
150000003839 salts Chemical group 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- 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
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
General Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA342,182A 1976-11-03 1979-12-18 OBTENTION DE 5'-PHOSPHATE DE 9-(.beta.-D- ARABINOFURANOSYL)ADENINE Expired CA1088927A (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US73842576A	1976-11-03	1976-11-03
US738,425		1976-11-03
US05/831,703 US4123609A (en)	1976-11-03	1977-09-12	Process for the production of 9-(β-D-arabinofuranosyl)adenine, 5'-phosphate
US831,703		1977-09-12

Publications (1)

Publication Number	Publication Date
CA1088927A true CA1088927A (fr)	1980-11-04

Family

ID=27113366

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA290,047A Expired CA1077030A (fr)	1976-11-03	1977-11-02	PROCEDE D'OBTENTION DE 5'-PHOSPHATE DE 9-(.beta.-D-ARABINOFURANOSYL) ADENINE
CA342,182A Expired CA1088927A (fr)	1976-11-03	1979-12-18	OBTENTION DE 5'-PHOSPHATE DE 9-(.beta.-D- ARABINOFURANOSYL)ADENINE

Family Applications Before (1)

Application Number	Title	Priority Date	Filing Date
CA290,047A Expired CA1077030A (fr)	1976-11-03	1977-11-02	PROCEDE D'OBTENTION DE 5'-PHOSPHATE DE 9-(.beta.-D-ARABINOFURANOSYL) ADENINE

Country Status (12)

Country	Link
JP (1)	JPS5356691A (fr)
AT (1)	AT358187B (fr)
CA (2)	CA1077030A (fr)
CH (1)	CH626377A5 (fr)
DE (1)	DE2749056A1 (fr)
DK (1)	DK151263C (fr)
ES (1)	ES463768A1 (fr)
FR (1)	FR2370057A1 (fr)
GB (1)	GB1559456A (fr)
HK (1)	HK3884A (fr)
NL (1)	NL191060C (fr)
SE (1)	SE442404B (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR1383572A (fr) *	1964-02-28	1964-12-24	Necchi Spa	Perfectionnements apportés aux dispositifs automatiques d'arrêt pour machine à coudre
DE1645896C3 (de) *	1965-03-17	1975-01-02	Ajinomoto Co., Inc., Tokio	Verfahren zur Herstellung von 5'-Ribonucleotiden nd S'-Desoxyribonucleotiden
BE756704A (fr) *	1969-09-26	1971-03-01	Parke Davis & Co	Procede de production du 5'-phosphate de 9-(beta-d- arabinofuranosyl) adenine et de ses sels

1977
- 1977-11-02 CH CH1335777A patent/CH626377A5/fr not_active IP Right Cessation
- 1977-11-02 DK DK487177A patent/DK151263C/da not_active IP Right Cessation
- 1977-11-02 NL NL7712102A patent/NL191060C/xx not_active IP Right Cessation
- 1977-11-02 FR FR7732871A patent/FR2370057A1/fr active Granted
- 1977-11-02 CA CA290,047A patent/CA1077030A/fr not_active Expired
- 1977-11-02 JP JP13216277A patent/JPS5356691A/ja active Pending
- 1977-11-02 ES ES463768A patent/ES463768A1/es not_active Expired
- 1977-11-02 SE SE7712368A patent/SE442404B/xx not_active IP Right Cessation
- 1977-11-02 GB GB4564777A patent/GB1559456A/en not_active Expired
- 1977-11-02 AT AT779577A patent/AT358187B/de not_active IP Right Cessation
- 1977-11-02 DE DE19772749056 patent/DE2749056A1/de active Granted
1979
- 1979-12-18 CA CA342,182A patent/CA1088927A/fr not_active Expired
1984
- 1984-01-12 HK HK3884A patent/HK3884A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
DK487177A (da)	1978-05-04
GB1559456A (en)	1980-01-16
DK151263C (da)	1988-05-16
ATA779577A (de)	1980-01-15
JPS5356691A (en)	1978-05-23
NL7712102A (nl)	1978-05-08
DE2749056A1 (de)	1978-05-18
NL191060B (nl)	1994-08-01
DE2749056C2 (fr)	1987-07-16
SE7712368L (sv)	1978-05-04
FR2370057A1 (fr)	1978-06-02
CA1077030A (fr)	1980-05-06
ES463768A1 (es)	1978-06-01
HK3884A (en)	1984-01-20
FR2370057B1 (fr)	1980-06-13
SE442404B (sv)	1985-12-23
NL191060C (nl)	1995-01-02
CH626377A5 (en)	1981-11-13
AT358187B (de)	1980-08-25
DK151263B (da)	1987-11-16

Legal Events

Date	Code	Title	Description
1997-11-04	MKEX	Expiry

Publication	Publication Date	Title
US20120178710A1 (en)	2012-07-12	Synthesis of cyclic diguanosine monophosphate and thiophosphate analogs thereof
US4123609A (en)	1978-10-31	Process for the production of 9-(β-D-arabinofuranosyl)adenine, 5'-phosphate
US3336289A (en)	1967-08-15	9-beta-d-ribofuranosyl-7-deazapurine 5'-phosphate esters
US3448098A (en)	1969-06-03	Production of guanylic acid
Maryanoff et al.	1984	Stereoselective synthesis and biological activity of. beta.-and. alpha.-D-arabinose 1, 5-diphosphate: analogs of a potent metabolic regulator
US2844514A (en)	1958-07-22	Process for the production of nucleotides
US3817978A (en)	1974-06-18	4-fluoro nucleosides and sugar intermediates, and methods of preparing
EP0071227B1 (fr)	1987-11-11	Bêta-glycosyl C-nucléosides à activité anti-leucémique
EP0002192B1 (fr)	1981-11-04	Synthèse enzymatique d'arabino-nucléosides
US3309358A (en)	1967-03-14	7-deazaadenine 2', 5'-and 3', 5'-dinucleoside phosphate and process therefor
US3036087A (en)	1962-05-22	Process for the preparation of phosphocreatine and/or phosphocreatinine
CA1077030A (fr)	1980-05-06	PROCEDE D'OBTENTION DE 5'-PHOSPHATE DE 9-(.beta.-D-ARABINOFURANOSYL) ADENINE
IL26147A (en)	1970-03-22	Deazapurine d-ribofuranoside cyclic 3',5'-phosphates and a process for their production
US6884880B2 (en)	2005-04-26	Process for the preparation of 9-β-anomeric nucleoside analogs
KR900002709B1 (ko)	1990-04-23	푸린-9-일알킬렌옥시메틸 포스폰산의 합성방법
US5124442A (en)	1992-06-23	Process for preparing azt (3'-azido-3'-deoxy-thymidine) and related compounds
US2795580A (en)	1957-06-11	Synthesis of nucleoside polyphosphates
IL25711A (en)	1970-07-19	5,5'-dinucleoside phosphates
JPS63135395A (ja)	1988-06-07	リン脂質誘導体及びその製造方法
EP0222172B1 (fr)	1991-02-06	Dérivé de l'acide N-glycolylneuraminique
US3428624A (en)	1969-02-18	Calcium sugar phosphate process
EP1464708A1 (fr)	2004-10-06	Procédé de préparation de fludarabine phosphate à partir de 2-fluoroadénine
FI115836B (fi)	2005-07-29	Epäsymmetristen fosforihappodiestereiden valmistusmenetelmä
CS214691B2 (en)	1982-05-28	Method of making the vindesine
Azhayev et al.	1977	Synthesis of acylamino acid esters of nucleoside 5′-phosphates and their investigation with PMR and CD spectra