Late-stage O-sulfation with a bioinspired sulfuryl donor

Area of Science:

• Organic Chemistry
• Biochemistry
• Chemical Biology

Background:

• O-sulfation is a crucial biomolecule modification, essential for various biological processes.
• Existing chemical sulfuryl donors often require harsh conditions and are unsuitable for complex molecules.
• Nature utilizes efficient sulfuryl donors like 3'-phosphoadenosine-5'-phosphosulfate (PAPS).

Purpose of the Study:

• To develop a mild and effective biomimetic O-sulfation method.
• To identify suitable sulfuryl donors for complex natural products and pharmaceutical scaffolds.
• To overcome the limitations of current chemical O-sulfation strategies.

Main Methods:

• Utilized p-nitrophenyl sulfate (PNPS) as the sulfuryl donor.
• Employed tetrabutylammonium (nBu4N+) as a counterion to activate PNPS.
• Investigated the coordination between nBu4N+ and the sulfate group of PNPS.

Main Results:

• The tetrabutylammonium counterion activates PNPS by elongating the S-O bond and improving the leaving group ability.
• Achieved biomimetic O-sulfation compatible with complex natural products and pharmaceutical scaffolds.
• Demonstrated site-selective O-sulfation of diverse alcohols and phenols under mild conditions.

Conclusions:

• The developed method offers a biomimetic and efficient approach to O-sulfation.
• This strategy enables selective sulfurylation of complex molecules under mild conditions.
• The findings present a valuable tool for modifying biomolecules and drug scaffolds.