Core diversification using 1,2-oxaborines as a versatile molecular platform.

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Drug discovery often requires synthesizing diverse analogues with varied core structures.
• Traditional de novo synthesis of these analogues is time-consuming and labor-intensive.

Purpose of the Study:

• To develop a novel and efficient strategy for rapid access to diverse core structures in drug discovery.
• To utilize 1,2-oxaborines as a versatile molecular platform for core diversification.

Main Methods:

• A soft enolization/6π-electrocyclization strategy was developed for efficient 1,2-oxaborine synthesis from enones or enals.
• 1,2-oxaborines were subjected to C-H functionalization and subsequent transformations.
• Late-stage diversification of a common intermediate was performed.

Main Results:

• A versatile 1,2-oxaborine platform was established for rapid synthesis of diverse molecular cores.
• 1,2-oxaborines demonstrated multifaceted reactivity, enabling transformation into various aromatic, heteroaromatic, and non-aromatic heterocycles.
• The strategy allowed for late-stage preparation of analogues with varied aromatic cores, including those with Lipitor substituents.

Conclusions:

• The 1,2-oxaborine-based core diversification strategy offers an efficient alternative to traditional de novo synthesis.
• This approach facilitates rapid access to a wide array of novel chemical entities for drug discovery.
• The methodology holds significant potential for accelerating the identification of new drug candidates.