Ynamide-Mediated Thioamide and Primary Thioamide Syntheses.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Green Chemistry

Background:

• Thioamides are important functional groups in medicinal chemistry.
• Traditional synthesis methods often involve toxic or expensive reagents and harsh conditions.
• Developing environmentally friendly and efficient thioamide synthesis is crucial.

Purpose of the Study:

• To develop an environmentally friendly and practical method for synthesizing thioamides and primary thioamides.
• To establish a racemization-free strategy for peptide C-terminal modification.
• To synthesize thioamide-modified drugs and thiazolyl-modified peptides.

Main Methods:

• Ynamide-mediated thioamidation of monothiocarboxylic acids with amines or ammonium hydroxide.
• Utilizing sodium hydrosulfide (NaSH) as the sulfur source.
• Employing simple and mild reaction conditions.

Main Results:

• The reaction demonstrated tolerance to various functional groups including hydroxyl, ester, tertiary amine, ketone, and amide.
• The use of NaSH avoided toxic, expensive, and malodorous organic sulfur reagents.
• Stereochemical integrity of α-chiral monothiocarboxylic acids was maintained throughout the process.
• Thioamide-modified drugs were synthesized in good yields.
• Primary thioamides were successfully transformed into backbone thiazolyl-modified peptides.

Conclusions:

• The ynamide-mediated thioamidation offers a green, practical, and efficient route to thioamides.
• This method provides a valuable tool for racemization-free peptide modifications and drug discovery.
• The protocol facilitates the synthesis of complex thioamide-containing molecules.