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US 2026/0152522 A1Published application
DNA-Compatible Wittig and Wittig-Related Olefination of on-DNA Peptidyl-Ylides and Beta-Keto Phosphonates for Development of on-DNA Peptidomimetics through Diversity-Oriented Synthesis (DOS)
AssigneeThe Rockefeller University
InventorsMarc Flajolet, Yashoda Sunkari
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Abstract
The present invention provides methods of generating diverse chemical structures on DNA through Wittig olefination of novel on-DNA phosphorane ylides and Homer-Wadsworth-Emmons reaction of on-DNA β-keto phosphonates. The methods of this invention provide access to DNA-encode libraries (DELs) of diverse peptides, peptidomimetics, chalcone-based molecules, and the like.
Claims19
A compound having a structure selected from the group consisting of:
- wherein DNA is a nucleic acid barcode;
- each instance of G is independently of the formula
- each occurrence of A1 and A2 is independently selected from the group consisting of H, halo, amino, thio, hydroxyl, C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C10 alkylthio, C3-C10 cycloalkyl, C1-C10 heteroalkyl, C2-C10 heterocyclyl, aryl, aryl-(C1-C4)alkyl, heteroaryl, and any combination thereof;
- each occurrence of R1, R2, and R3 is independently selected from the group consisting of H, F, Cl, Br, I, N(R4)2, OH, SH, an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 alkenyl, an optionally substituted C1-C10 alkynyl, an optionally substituted C1-C10 alkoxy, an optionally substituted C1-C10 alkylamino, an optionally substituted C1-C10 alkylthio, an optionally substituted C3-C10 cycloalkyl, an optionally substituted C1-C10 heteroalkyl, optionally substituted C2-C10 heterocyclyl, an optionally substituted aryl, an optionally substituted aryl-(C1-C4)alkyl, an optionally substituted heteroaryl, an optionally substituted aminoaryl, fluorenylmethyloxycarbonyl, tert-butyloxycarbonyl, benzyloxycarbonyl, acetyl, trifluoroacetyl, phthalimidyl, benzyl, triphenylmethyl, benzylidenyl, and tosyl;
- Y is selected from the group consisting of OH, SH, and NR4;
- each occurrence of R4 is independently selected from the group consisting of H, an optionally substituted C1-C10 alkyl, and an optionally substituted aryl-(C1-C4)alkyl;
- each occurrence of t is independently an integer of 1-10;
- and
- n is an integer of 1-20.
6 more elements
(canceled)
10-14. (canceled)
A compound having a structure selected from the group consisting of:
- wherein each instance of G is independently of the formula
- each occurrence of A1 and A2 is independently selected from the group consisting of H, halo, amino, thio, hydroxyl, C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C10 alkylthio, C3-C10 cycloalkyl, C1-C10 heteroalkyl, C2-C10 heterocyclyl, aryl, aryl-(C1-C4)alkyl, heteroaryl, and any combination thereof;
- each occurrence of R2 and R3 is independently selected from the group consisting of H, F, Cl, Br, I, N(R4)2, OH, SH, an optionally substituted C1-C10 alkyl, an optionally substituted C1-C10 alkenyl, an optionally substituted C1-C10 alkynyl, an optionally substituted C1-C10 alkoxy, an optionally substituted C1-C10 alkylamino, an optionally substituted C1-C10 alkylthio, an optionally substituted C3-C10 cycloalkyl, an optionally substituted C1-C10 heteroalkyl, optionally substituted C2-C10 heterocyclyl, an optionally substituted aryl, an optionally substituted aryl-(C1-C4)alkyl, an optionally substituted heteroaryl, an optionally substituted aminoaryl, fluorenylmethyloxycarbonyl, tert-butyloxycarbonyl, benzyloxycarbonyl, acetyl, trifluoroacetyl, phthalimidyl, benzyl, triphenylmethyl, benzylidenyl, and tosyl;
- Y is selected from the group consisting of OH, SH, and NR4;
- each occurrence of R4 is independently selected from the group consisting of H, an optionally substituted C1-C10 alkyl, and an optionally substituted aryl-(C1-C4)alkyl;
- each occurrence of R5, R6, R7, R8, and R9 is independently selected from the group consisting of H, halo, amino, thio, hydroxyl, C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C10 alkylthio, C3-C10 cycloalkyl, C1-C10 heteroalkyl, C2-C10 heterocyclyl, aryl, aryl-(C1-C4)alkyl, heteroaryl, and any combination thereof;
- each occurrence of t is independently an integer of 1-10;
- and
- n is an integer of 1-20.
6 more elements
17-22. (canceled)
An on-DNA phosphorane-ylide compound having a structure selected from the group consisting of:
- wherein each occurrence of R5, R6, R7, R8, and R9 is independently selected from the group consisting of H, halo, amino, thio, hydroxyl, C1-C10 alkyl, C1-C10 alkenyl, C1-C10 alkynyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C10 alkylthio, C3-C10 cycloalkyl, C1-C10 heteroalkyl, C2-C10 heterocyclyl, aryl, aryl-(C1-C4)alkyl, heteroaryl, and any combination thereof, and
- the protecting group is selected from the group consisting of fluorenylmethyloxycarbonyl, tert-butyloxycarbonyl, benzyloxycarbonyl, acetyl, trifluoroacetyl, phthalimidyl, benzyl, triphenylmethyl, benzylidenyl, and tosyl.
26-27. (canceled)
(canceled)
Dependencies are inferred from the claim text.