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US 2024/0190924 A1Published application
Synthesis of Gamma Peptide Nucleic Acid Monomers and Oligomers, and Applications Therefor
AssigneeCarnegie Mellon University
InventorsDanith H. Ly, Shivaji A. Thadke, Isha Dhami
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Abstract
Provided herein are methods of preparing gamma-peptide nucleic acid monomers, and methods of synthesizing gamma-peptide nucleic acid oligomers.
Claims25
A method of making a peptide nucleic acid monomer, comprising:
- phosphorylating compound 1, where n is 1, 2, 3, or 4, R1 is an amine-protecting group:
- with trichlorophosphorus (PCl3), phosphoramidous acid, N,N-bis(1-methylethyl)-, bis(phenylmethyl) ester, or 4,3-Benzodioxaphosphepin, 3-chloro-1,5-dihydro-, 3-oxide), R2—OH, and R3—OH, to produce compound 2, where R2 and R3 are, independently, H benzyl
- t-butyl, propionitrilyl
- or 4-nitrophenylethylenyl
- reducing compound 2 to produce compound 3:
- reacting compound 3 with Des s-Martin periodinane, followed by treating with NH2CH2C(O)OCH3 and DCM, or reacting compound 3 with DMSO:TEA followed by treating with NH2CH2C(O)OCH3, to produce compound 4:
- and
- conjugating compound 4 with a nucleobase by reacting compound 4 with RCH2C(O)OH, where R is a nucleobase in which α-amines of R are protected with an amine-protecting group to produce compound 5:
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A method of making a peptide nucleic acid monomer, comprising:
- reducing compound 6:
- where R4 is an amine-protecting group, and one of R5 and R6 is H, and the other of R5 and R6 is:
- where m is 1, 2, 3, or 4,
- to produce compound 7:
- reacting compound 7 with Dess-Martin periodinane, followed by treating with NH2CH2C(O)OCH3 (methyl glycinate), or reacting compound 7 with DMSO:TEA followed by treating with NH2CH2C(O)OCH3, to produce compound 8:
- conjugating compound 8 with a nucleobase by reacting compound 8 with RCH2C(O)OH, where R is a nucleobase in which α-amines of R are protected with an amine-protecting group to produce compound 9:
- and
- Removing the terminal methyl group of 9 to produce compound 10:
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A compound having the structure:
- where R2 and R3 are, independently, H, benzyl, t-butyl, propionitrilyl, or 4-nitrophenylethylenyl, or a salt thereof.
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Dependencies are inferred from the claim text.