DP4+-Based Stereochemical Reassignment and Total Synthesis of Polyenic Macrolactam Muanlactam

Area of Science:

• Organic Synthesis
• Natural Product Chemistry
• Stereochemistry

Background:

• Muanlactam is a polyenic macrolactam with a previously assigned structure.
• Computational predictions (DP4+) suggested a different stereoisomer than the reported natural product.
• Clarification of the natural product's structure is essential for further research.

Purpose of the Study:

• To perform the total synthesis of the muanlactam stereoisomer predicted by DP4+ calculations.
• To unequivocally confirm the structure and relative configuration of the polyenic macrolactam.
• To correct the previously assigned stereochemistry of the natural product at C19.

Main Methods:

• Iterative enantio- and diastereoselective Krische's allylation for syn-1,3-diol construction.
• Stereoselective synthesis of enantiopure amine fragment using Ellman's chiral auxiliary.
• Suzuki-Miyaura cross-coupling for conjugated diene and triene unit assembly.
• Horner-Wadsworth-Emmons condensation for conjugated tetraene formation.
• Challenging macrolactamization using HATU and DIPEA.

Main Results:

• Successful total synthesis of the muanlactam stereoisomer predicted by DP4+.
• Full confirmation of the polyenic macrolactam structure.
• NMR data of the synthetic product matched the natural product, validating the corrected C19 configuration.

Conclusions:

• The total synthesis unequivocally confirmed the structure of muanlactam.
• The study corrected the relative configuration at C19, revising the initial assignment based on DP4+ calculations.
• This work provides a reliable synthetic route and corrected structural information for muanlactam.