Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling Oxidation Strategy

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Process Chemistry

Background:

• HIV maturation inhibitors are crucial for antiretroviral therapy.
• BMS-955176 is a promising HIV maturation inhibitor.
• Efficient and scalable synthesis is vital for drug development.

Purpose of the Study:

• To develop a second-generation, concise, and scalable synthesis of BMS-955176.
• To utilize readily available starting materials like betulin.
• To optimize key chemical transformations for improved yield and efficiency.

Main Methods:

• Employing a Cu(I)-mediated aerobic oxidation of betulin.
• Utilizing a PIFA-mediated dehydrogenation of an oxime.
• Leveraging a unique Lossen rearrangement for C17 amino group installation.

Main Results:

• A 7-step synthetic route was established.
• The synthesis achieved an overall yield of 47%.
• The process begins with the abundant natural product betulin.

Conclusions:

• The described synthesis is concise and scalable.
• This route provides an efficient method for producing BMS-955176.
• The strategy highlights novel oxidation and rearrangement reactions.