Efficient Buchwald-Hartwig-Migita Cross-Coupling for DNA Thioglycoconjugation

Area of Science:

• Organic Chemistry
• Nucleic Acid Chemistry
• Medicinal Chemistry

Background:

• Oligonucleotides (ODNs) are crucial in various biological processes and therapeutic applications.
• Thioglycosylation of ODNs can enhance their stability and biological activity.
• Efficient and mild conjugation methods are needed for synthesizing modified ODNs.

Purpose of the Study:

• To develop an efficient and mild method for the thioglycoconjugation of iodinated oligonucleotides.
• To enable the synthesis of diverse functionalized thioglycosylated ODNs.
• To ensure the integrity of other nucleobases during the conjugation process.

Main Methods:

• Utilized Buchwald-Hartwig-Migita cross-coupling reaction.
• Employed mild reaction conditions.
• Focused on iodinated oligonucleotides as substrates.

Main Results:

• Achieved efficient thioglycoconjugation of iodinated oligonucleotides.
• Demonstrated divergent synthesis of various functionalized thioglycosylated ODNs.
• Obtained good yields for the synthesized compounds.
• Confirmed that the method does not affect the integrity of adenine (A), cytosine (C), and guanine (G) nucleobases.

Conclusions:

• The reported Buchwald-Hartwig-Migita cross-coupling method is effective for thioglycoconjugation of iodinated ODNs.
• This method provides a versatile route for synthesizing diverse thioglycosylated ODNs under mild conditions.
• The method is compatible with standard oligonucleotide bases, preserving their integrity.