Stereoselective one-pot synthesis of polypropionates

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Natural Product Synthesis

Background:

• Polypropionates, characterized by alternating methyl and hydroxy groups, are vital structural motifs in numerous bioactive natural products.
• The synthesis of polypropionates is challenging due to the need for precise control over contiguous stereocentres and operational simplicity.

Purpose of the Study:

• To develop an efficient and stereoselective strategy for assembling polypropionates with three or four stereocentres.
• To demonstrate a versatile relay process applicable to complex molecule synthesis.

Main Methods:

• A three-step relay process involving Diels-Alder reaction, silylenol ether hydrolysis, and Baeyer-Villiger oxidation.
• Stereochemical outcomes are dictated by the substitution patterns of Diels-Alder substrates.
• The sequence can be performed in one pot for enhanced efficiency.

Main Results:

• Successful stereoselective synthesis of polypropionates with three or four stereocentres.
• Demonstrated the ability to construct the C1-C9 segment of the macrolide etnangiens, establishing four stereocentres.
• The relay sequence offers potential for iterative elaboration of polypropionate chains.

Conclusions:

• The developed three-step relay process provides an efficient and versatile method for stereoselective polypropionate synthesis.
• This strategy simplifies the assembly of complex polypropionate structures found in valuable natural products.
• The method holds promise for the total synthesis of complex natural products and drug discovery efforts.