On-DNA Palladium-Catalyzed Hydrogenation-like Reaction Suitable for DNA-Encoded Library Synthesis.

Area of Science:

• Organic Chemistry
• Biochemistry
• Synthetic Chemistry

Background:

• Protecting groups are essential in complex organic synthesis, particularly in DNA chemistry.
• Orthogonal deprotection strategies are crucial for selective functionalization.
• Existing methods often lack efficiency or compatibility with aqueous DNA conditions.

Purpose of the Study:

• To develop a novel, orthogonal method for removing common amine and carboxylic acid protecting groups on DNA.
• To establish conditions compatible with aqueous DNA environments.
• To expand the utility by including reduction of unsaturated bonds and specific functional groups.

Main Methods:

• Utilized sodium borohydride (NaBH4) as the hydrogen source.
• Employed palladium(II) acetate (Pd(OAc)2) as the catalyst.
• Performed reactions under aqueous DNA conditions, demonstrating compatibility.

Main Results:

• Successfully achieved orthogonal removal of N-Cbz, N-Alloc, N-Allyl, O-Bn, and O-Allyl protecting groups.
• Demonstrated efficient hydrogenation of triple and double bonds to saturated compounds.
• Introduced a new procedure for reducing azides and aromatic nitro compounds to primary amines.

Conclusions:

• The developed Pd-catalyzed method offers a versatile and efficient approach for orthogonal deprotection in DNA chemistry.
• The conditions are mild and suitable for sensitive biomolecules.
• This method expands the synthetic toolkit for DNA modification and functionalization.