| Autor: |
Mihara Y; College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577, Japan., Kadoya H; College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577, Japan., Kakihana S; College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577, Japan., Kotoku N; College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga 525-8577, Japan. |
| Abstrakt: |
A novel and concise synthetic method for arenastatin A, a cytotoxic cyclic depsipeptide of marine origin, was developed in this study. The convergent assembly of the four segments, including the cross-metathesis reaction, gave a cyclization precursor, and Fmoc deprotection caused simultaneous macrocyclization. The Corey-Chaykovsky reaction using a chiral sulfur ylide afforded arenastatin A with complete stereoselectivity in the longest linear sequence of seven reaction steps from the known compound. Using this synthetic method, some analogs of segment B were prepared through a late-stage diversification strategy. The simple S N 2 reaction of the thiolate toward the tosylate precursor, prepared using almost the same synthetic method as described above, provided the desired sulfide analogs. |
