# US 8,785,619 B1 · Nucleosides and oligonucleotides for studies on reversal of cytotoxic and mutagenic damage of DNA potential diagnostics tools

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- Number: US 8,785,619 B1
- Document ID: US8785619B1
- Status: Granted
- Kind: B1
- Application number: 11/018,567
- Filed: 2004-12-20
- Granted: 2014-07-22
- Earliest claimed: 2003-12-20
- Assignees: ChemGenes Corporation
- Applicants: Sant K. Srivastav; Suresh C. Srivastava; Satya P Bajpai
- Inventors: Sant K. Srivastav; Suresh C. Srivastava; Satya P Bajpai
- Web page: https://patentgrep.com/patent/US8785619B1

## CPC

- C07H 21/00: Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H 19/06: Pyrimidine radicals
- C07H 19/16: Purine radicals
- Y02P 20/55: Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS

## Abstract

This invention relates to n-alkylated synthetic nucleosides and phosphoramidites of high regio-specific purity and stability and for selective deprotection of the protecting group in oligonucleotides for the purpose of synthesis of high purity selectively n-alkylated sequence specific DNA and RNA. Such oligonucleotides are useful for study of mechanism of cytotoxic and mutagenic DNA damage, detection and reversal of cellular cytotoxic and mutagenic damages that occurs from the incorporation of methylated nucleosides, the corresponding phosphates and triphosphates and their precursors, via de novo DNA synthesis. The reagents could be extremely valuable tools as diagnostics and mutagenic reversal reagents. The present invention describes N-1-nitrogen alkylated purine and N-3 nitrogen alkylated pyrimidines with appropriate nucleobase amino protection, which are selectively deprotected with minimal migration of the alkyl substituent under the condition which are required for synthesizing high purity regiospecific N-1 and N-3 nitrogen alkylated oligonucleotides. A novel process has been developed to synthesize N-3 nitrogen alkylated cytidine.

## Claims

### Claim 1

A nucleoside of the following formula:
wherein:
R1 is methyl;
Y is monomethoxytrityl, dimethyoxytrityl, trimethoxytrityl, or tetrahydropyranyl;
R′ is a phosphoramidite;
Z is hydrogen, fluoro, or protected amino;
said phosphoramidite is denoted by
P—N(R2,R3)(OCH2CH2CN) or P—N(R2,R3)(OR4),
wherein R2 and R3 are selected from the group consisting of diisopropyl, diethyl, dimethyl, morpholino, and pyrrolidino; and
R4 is a lower alkyl containing 1-6 carbon atoms; and
R5 is phenoxy acetyl or 9-fluorenylmethoxycarbonyl.

### Claim 2 (depends on 1)

A method of synthesizing a defined sequence of an oligo-2′-deoxyribonucleotide, comprising the step of:
reacting the nucleoside of claim 1 with an oligo-2′-deoxyribonucleotide, to produce said defined sequence of the oligo-2′-deoxyribonucleotide.