Total synthesis of (+)-SCH 351448

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• (+)-SCH 351448 is a C(2)-symmetric macrodiolide with potential therapeutic applications.
• Efficient synthetic routes are crucial for the development and large-scale production of complex natural products and drug candidates.

Purpose of the Study:

• To describe a convergent synthesis of (+)-SCH 351448.
• To establish a reliable method for assembling the pyran subunits and achieving macrocyclization.

Main Methods:

• A [4 + 2] annulation reaction using a chiral allyl silane (anti-5c) to construct pyran subunits.
• Stepwise homodimerization involving esterification and macrocyclization to form the macrodiolide.

Main Results:

• Successful convergent synthesis of (+)-SCH 351448.
• The [4 + 2] annulation effectively assembled the pyran subunits.
• Stepwise homodimerization yielded the target macrodiolide.

Conclusions:

• The developed synthetic strategy provides an efficient route to (+)-SCH 351448.
• This approach is valuable for the synthesis of C(2)-symmetric macrodiolides.