Nine‐Step Total Synthesis and Biological Evaluation of Rhizonin A

Abstract

of main observation and conclusion We have achieved the total synthesis of an architecturally and biologically intriguing cyclic polypeptide, rhizonin A (1), in an exceptionally concise and convergent fashion. The strategic route entails 9 longest linear steps to elaborate commercially available materials into the natural product with an overall yield of 9.7%. The brevity of sequence and high overall yield was fueled by the judicious selection of chemical tactics. Rhizonin A (1) showed weak inhibitory effects on the cell viability of HCT116 colorectal cancer cells and this activity was dependent on hypoxia-inducible factors.

Concise Total Synthesis of Dysoxylactam A and a Simplified Analog

“…[ 13,40 ] The ester 14 was treated with TFA in dichloromethane (1 : 3) to remove the Boc group, and gave a TFA salt, which was then directly reacted with 6‐heptenoic acid in the presence of HATU and Hunig's base to afford the key diene amide 2 in 98% yield. [ 41 ] Next, ring‐closing olefin metathesis was used for the vital macrocyclization. The treatment of diene amide 2 with 10% the second‐generation Grubbs catalyst (G‐II) in dichloromethane at 40°C followed by cooling and concentration produced the desired Bn‐protected macrocyclic key intermediate, which was directly subjected to the next deprotection step without purification in a one‐pot way in the presence of Pd/C under H 2 atmosphere to afford target product dysoxylactam A ( 1 ) in 83% yield.…”