Cyclodepsipeptide alveolaride C: total synthesis and structural assignment.

Area of Science:

• Organic Chemistry
• Natural Product Synthesis

Background:

• Cyclodepsipeptides are a class of natural products with diverse biological activities.
• Alveolaride C is a naturally occurring cyclodepsipeptide whose stereochemistry required unambiguous assignment.

Purpose of the Study:

• To achieve the first stereoselective total synthesis of alveolaride C.
• To unambiguously establish the stereochemistry of three chiral centers in the nonpeptidic segment.
• To revise the stereochemistry of the proposed β-phenylalanine moiety.

Main Methods:

• Convergent synthesis strategy.
• Sharpless asymmetric dihydroxylation for vicinal diol installation.
• Julia-Kocienski olefination for aliphatic side chain construction.
• Shiina protocol for esterification, amide coupling, and macrolactamization for ring formation.

Main Results:

• Successful stereoselective total synthesis of alveolaride C.
• Unambiguous determination of stereochemistry for three chiral centers.
• Revision of the stereochemistry of the β-phenylalanine component.

Conclusions:

• The synthetic route provides a reliable method for accessing alveolaride C.
• The established stereochemistry clarifies the molecular structure of this bioactive natural product.
• This work contributes to the understanding and synthesis of complex cyclodepsipeptides.