EP0064796A2
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EP
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Phosphorylating agent and process for the phosphorylation of organic hydroxyl compounds
Assignee: Unilever PLC
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Filing: 1982-05-10
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Granted: —
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Expires: 2002-05-10
Abstract
Abstract The invention relates to new phosphorylating agents, a process for producing said compounds and their use in a process for the phosphorylation of organic hydroxyl compounds to obtain intermediate products useful for the production of polynucleotides. The phosphorylation is achieved without side reactions at the purine- or pyrimidine bases.
Inventors
- 👤 Jacobus Hubertus Van Boom
- 👤 Gijsbert Arie Van Der Marel
- 👤 Constant Adriaan Anton Van Boeckel
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-28 21:06
CPC Classifications
C; C07; C07H; C07H21/00; C07F; C07F9/00; C07F9/02; C07F9/547; C07F9/6515; C07F9/6518; C07F9/65188
Claims Analysis
Total Claims: 48
Claim 1
Independent Claim
57 words
Phosphoric acid derivatives having formula 1 of the formula sheet, in which R 1 , R 2 , R 3 and R 4 are alkyl groups having 1 - 4 C-atoms and/or hydrogen and in which Z is O R 5 in which R 5 is alkyl or aryl or Z is a primary or secondary amine.
Claim 2
Dependent Claim
57 words
Phosphoric acid derivatives having formula 1 of the formula sheet, in which R 1 , R 2 , R 3 and R 4 are alkyl groups having 1 - 4 C-atoms and/or hydrogen and in which Z is O R 5 in which R 5 is alkyl or aryl or Z is a primary or secondary amine.
Claim 3
Dependent Claim
45 words
Phosphoric acid derivatives according to claim 1, characterized in that R l =R 2 = R 3 = R 4 is hydrogen and Z is a morpholino group or an OR group in which R 5 is a 2-halophenyl- a 4-halophenyl- or a 2-halo-4-alkylphenyl group.
Claim 4
Dependent Claim
69 words
Process for the preparation of phosphoric acid derivatives according to claim 1 or 2, characterized in that a compound with formula 2, in which X is a halogen atom and Z has the same meaning as in formula 1, is reacted with a compound with formula 3 , in which R 1 , R 2 , R 3 , R 4 have the same meaning as in formula 1.
Claim 5
Dependent Claim
26 words
Process according to claim 3, characterized in that the reaction is carried out in the presence of a tertiary amine base and an inert organic solvent.
Claim 6
Dependent Claim
45 words
Process according to claims 3 and 4, characterized in that a compound with formula 2, in which X = Cl is reacted in the presence of pyridine with a compound with formula 3, in which R 1 =R 2 =R 3 =R 4 is hydrogen.
Claim 7
Dependent Claim
24 words
Process for phosphorylating a hydroxyl compound, characterized in that the hydroxyl compound is reacted with phosphoric acid derivatives according to claim 1 or 2.
Claim 8
Dependent Claim
18 words
Process according to claim 6, characterized in that the hydroxyl compound is a monosaccharide or a derivative thereof.
Claim 9
Dependent Claim
19 words
Process according to claim 7, characterized in that the hydroxyl compound is a nucleoside, a nucleotide or a polynucleotide.'
Claim 10
Dependent Claim
36 words
Process according to claim 8, characterized in that the hydroxyl compound is a nucleoside or a 3'-5'-polynucleotide containing a free 5'-hydroxyl group and a protected 3'-hydroxyl group,and of which any other reactive groups present are protected.
Claim 11
Dependent Claim
37 words
Process according to claim 8, characterized in that the hydroxyl compound is a nucleoside or a 3'-5'-polynucleotide having a free 3'hydroxyl group and a protected 5'-hydroxyl group and of which any other reactive groups present are protected.
Claim 12
Dependent Claim
22 words
Process according to claim 6, characterized in that the hydroxyl compound is a protected DNA- or RNA-fragment having a free hydroxyl group.
Claim 13
Dependent Claim
22 words
Process according to claim 11, characterized in that the hydroxyl group is a protected RNA-fragment having a free 5'- or 3'-hydroxyl group.
Claim 14
Dependent Claim
21 words
Phosphorylated compounds obtained by applying the process according to any one of claims 6 - 12 which particularly satisfy formula 4.
Claim 15
Dependent Claim
75 words
Process for the preparation of phosphotriester derivatives with formula 5, in which B is a protected or non-protected purine or pyrimidine base, Y is a group protecting the 5'-OH group and Z has the same meaning as in formula 1, and R 6 is an alkyl halogenide-, alkylcyanide-4-nitrophenylethyl- or 5-chloro-8-quinolyl group, characterized in that a compound with formula 4 is converted with an alcohol R 6 0H in the presence of a tertiary amine base.
Claim 16
Dependent Claim
75 words
Process for the preparation of phosphotriester derivatives with formula 5, in which B is a protected or non-protected purine or pyrimidine base, Y is a group protecting the 5'-OH group and Z has the same meaning as in formula 1, and R 6 is an alkyl halogenide-, alkylcyanide-4-nitrophenylethyl- or 5-chloro-8-quinolyl group, characterized in that a compound with formula 4 is converted with an alcohol R 6 0H in the presence of a tertiary amine base.
Claim 17
Dependent Claim
18 words
Process according to claim 14, characterized in that Y is a t-butyldimethylsilyl group or a dimethoxy trityl group.
Claim 18
Dependent Claim
27 words
Process according to claim 14, characterized in that B is a cytosine protected by anisoyl, a guanidine protected by diphenyl acetyl, or an adenine protected by benzoyl.
Claim 19
Dependent Claim
18 words
Process according to claim 14, characterized in that the reaction is carried out in the presence of pyridine.
Claim 20
Dependent Claim
18 words
Process according to claim 14, characterized in that the reaction is carried out in the presence of N-methylimidazole.
Claim 21
Dependent Claim
7 words
Phosphorylated 5'-protected d-nucleoside intermediates with formula 5.
Claim 22
Dependent Claim
7 words
Phosphorylated 5'-protected d-nucleoside intermediates with formula 5.
Claim 23
Dependent Claim
40 words
Process for the preparation of polynucleotides, in which 3'-5'-internucleotide phosphotriester compounds are obtained, characterized in that phosphorylated 5'-protected d-nucleoside intermediates having formula 4 are converted with a compound having formula 5 in which the protecting group Y has been removed.
Claim 24
Dependent Claim
40 words
Process for the preparation of polynucleotides, in which 3'-5'-internucleotide phosphotriester compounds are obtained, characterized in that phosphorylated 5'-protected d-nucleoside intermediates having formula 4 are converted with a compound having formula 5 in which the protecting group Y has been removed.
Claim 25
Dependent Claim
13 words
Process according to claim 20, characterized in that a solid carrier is used.
Claim 26
Dependent Claim
13 words
Process according to claim 21, characterized in that a functionalised carrier is used.
Claim 27
Dependent Claim
118 words
A process for the preparation of phosphoric acid derivatives, characterized in that phosphoric acid derivatives of formula 1, in which R 1 , R 2 , R 3 , R 4 are alkyl groups having 1 - 4 carbon atoms and/or hydrogen and in which Z is OR 5 in which R 5 is alkyl or aryl or Z is a primary or secondary amine, are produced by reacting a compound with formula 2, in which X is a halogen atom and Z has the same meaning as in formula 1, with a compound with formula 3, in which R 1 , R 2 , R 3 , R 4 have the same meaning as in formula 1.
Claim 28
Dependent Claim
118 words
A process for the preparation of phosphoric acid derivatives, characterized in that phosphoric acid derivatives of formula 1, in which R 1 , R 2 , R 3 , R 4 are alkyl groups having 1 - 4 carbon atoms and/or hydrogen and in which Z is OR 5 in which R 5 is alkyl or aryl or Z is a primary or secondary amine, are produced by reacting a compound with formula 2, in which X is a halogen atom and Z has the same meaning as in formula 1, with a compound with formula 3, in which R 1 , R 2 , R 3 , R 4 have the same meaning as in formula 1.
Claim 29
Dependent Claim
55 words
A process according to claim 1, characterized in that a phosphoric acid derivative is produced in which R 1 , R 2 , R 3 , R 4 are all hydrogen atoms and Z is a morpholino group or an OR 5 group in which R 5 is a 2-halophenyl-, a 4-halophenyl- or a 2-halo-4-alkylphenyl-group.
Claim 30
Dependent Claim
27 words
A process according to claim 1, characterized in that the reaction is carried out in the presence of a tertiary amine base and an inert organic solvent.
Claim 31
Dependent Claim
47 words
A process according to claim 1, characterized in that a compound with formula 2, in which X = Cl is reacted in the presence of pyridine with a compound with formula 3, in which R l = R 2 = R 3 = R 4 is hydrogen.
Claim 32
Dependent Claim
27 words
A process for phosphorylating a hydroxyl compound, characterized in that the hydroxyl compound is reacted with phosphoric acid derivatives obtained according to . claim 1 or 2.
Claim 33
Dependent Claim
19 words
A process according to claim 5, characterized in that the hydroxyl compound is a monosaccharide or a derivative thereof.
Claim 34
Dependent Claim
20 words
A process according to claim 6, characterized in that the hydroxyl compound is a nucleoside, a nucleotide or a polynucleotide.
Claim 35
Dependent Claim
37 words
A process according to claim 7, characterized in that the hydroxyl compound is a nucleoside or a 3'-5'-polynucleotide containing a free 5'-hydroxyl group and a protected 3'-hydroxyl group,and of which any other reactive groups present are protected.
Claim 36
Dependent Claim
38 words
A process according to claim 7, characterized in that the hydroxyl compound is a nucleoside or a 3'-5'-polynucleotide having a free 3'hydroxyl group and a protected 5'-hydroxyl group and of which any other reactive groups present are protected.
Claim 37
Dependent Claim
23 words
A process according to claim 5, characterized in that the hydroxyl compound is a protected DNA- or RNA-fragment having a free hydroxyl group.
Claim 38
Dependent Claim
23 words
A process according to claim 10, characterized in that the hydroxyl group is a protected RNA-fragment having a free 5'- or 3'-hydroxyl group.
Claim 39
Dependent Claim
74 words
A process for the preparation of phosphotriester derivatives with formula 5, in which B is a protected or non-protected purine or pyrimidine base, Y is a group protecting the 5'-OH group and Z has the same meaning as in formula 1, and R 6 is an alkyl halogenide-, alkylcyanide-4-nitrophenylethyl- or 5-chloro-8-quinolyl group, characterized in that a compound with formula 4 is converted with an alcohol R60H in the presence of a tertiary amine base.
Claim 40
Dependent Claim
74 words
A process for the preparation of phosphotriester derivatives with formula 5, in which B is a protected or non-protected purine or pyrimidine base, Y is a group protecting the 5'-OH group and Z has the same meaning as in formula 1, and R 6 is an alkyl halogenide-, alkylcyanide-4-nitrophenylethyl- or 5-chloro-8-quinolyl group, characterized in that a compound with formula 4 is converted with an alcohol R60H in the presence of a tertiary amine base.
Claim 41
Dependent Claim
19 words
A process according to claim 12, characterized in that Y is a t-butyldimethylsilyl group or a dimethoxy trityl group.
Claim 42
Dependent Claim
28 words
A process according to claim 12, characterized in that B is a cytosine protected by anisoyl, a guanidine protected by diphenyl acetyl, or an adenine protected by benzoyl.
Claim 43
Dependent Claim
19 words
A process according to claim 12, characterized in that the reaction is carried out in the presence of pyridine.
Claim 44
Dependent Claim
19 words
A process according to claim 12, characterized in that the reaction is carried out in the presence of N-methylimidazole.
Claim 45
Dependent Claim
41 words
A process for the preparation of polynucleotides, in which 3'-5'-internucleotide phosphotriester compounds are obtained, characterized in that phosphorylated 5'-protected d-nucleoside intermediates having formula 4 are converted with a compound having formula 5 in which the protecting group Y has been removed.
Claim 46
Dependent Claim
41 words
A process for the preparation of polynucleotides, in which 3'-5'-internucleotide phosphotriester compounds are obtained, characterized in that phosphorylated 5'-protected d-nucleoside intermediates having formula 4 are converted with a compound having formula 5 in which the protecting group Y has been removed.
Claim 47
Dependent Claim
14 words
A process according to claim 17, characterized in that a solid carrier is used.
Claim 48
Dependent Claim
14 words
A process according to claim 18, characterized in that a functionalised carrier is used.
References Cited (Backward Citations)
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