Total synthesis of cyclomarin C

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Cyclomarins are a class of natural products with potential biological activities.
• The total synthesis of complex cyclic peptides like cyclomarin C presents significant challenges.
• Previous synthetic efforts have been limited, necessitating novel approaches.

Purpose of the Study:

• To achieve the total synthesis of cyclomarin C.
• To develop efficient methodologies for preparing non-canonical amino acids required for cyclomarin synthesis.
• To establish optimal conditions for macrocyclization in the synthesis of cyclomarins.

Main Methods:

• A convergent synthetic strategy was employed, combining a tetrapeptide fragment and a tripeptide fragment.
• Novel methods were developed for the synthesis of non-canonical amino acids.
• Careful selection and application of protecting groups for peptide fragments were crucial.
• The optimal site for macrocyclization was identified and utilized.

Main Results:

• The total synthesis of cyclomarin C was successfully accomplished.
• Efficient methods for preparing key non-canonical amino acids were established.
• The macrocyclization step was optimized, leading to the desired product.
• The synthetic strategy demonstrated its applicability to other cyclomarin analogs.

Conclusions:

• The convergent synthesis of cyclomarin C is feasible and efficient.
• The developed methodologies for non-canonical amino acid synthesis and macrocyclization are valuable for future cyclomarin research.
• This work lays the foundation for the synthesis of other cyclomarin family members.