Asymmetric Total Syntheses of Marine Cyclic Depsipeptide Halipeptins A-D

• Published in: Chemistry : a European journal 2006-08, Vol.12 (25), p.6572-6584
• Main Authors: Yu, Shouyun, Pan, Xianhua, Ma, Dawei
• Format: Article
• Language: English
• Subjects: Alanine - analogs & derivatives; Alanine - chemistry; Amino Acids - chemical synthesis; Amino Acids - chemistry; Animals; cyclic depsipeptides; Decanoic Acids - chemistry; Depsipeptides - chemical synthesis; Isoleucine - analogs & derivatives; Isoleucine - chemistry; macrocyclization; natural products; Peptides, Cyclic - chemical synthesis; Porifera - chemistry; total synthesis; unnatural amino acids
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200600383

Halipeptins A–D (1 a–d) are a family of natural cyclic depsipeptides isolated from marine sponges. Total syntheses of these four compounds are detailed in this report. The key elements in this synthesis include the elaboration of the polysubstituted decanoic acid parts by two asymmetric aldol reactions, assembly of the N‐methyl‐δ‐hydroxyisoleucine residue by using either aza‐Claisen rearrangement or methylation of aspartates as the key steps, and macrocyclization at the polysubstituted decanoic acid alanine site. A family synthesis! Total syntheses for all of the members of the halipeptin family are detailed in this report. The key elements in these syntheses include the elaboration of the polysubstituted decanoic acid parts by two asymmetric aldol reactions, assembly of the N‐methyl‐δ‐hydroxyisoleucine residue by using either aza‐Claisen rearrangement or methylation of aspartates as the key steps, and macrocyclization at the polysubstituted decanoic acid alanine site.