Synthesis of the C5-C30 fragment of cyclodidemniserinol trisulfate via I2-mediated deprotection and ring closure tandem reaction

The marine natural product cyclodidemniserinol trisulfate displayed moderate HIV-1 integrase inhibitory activity. Its novel structure triggered our interest to synthesize it. In our total synthesis effort, the natural product was dissected into four fragments based on the rational retrosynthetic analysis. All four fragments were successfully prepared with orthogonal protection. And the assembly of fragment A and B furnished the C5-C30 key subunit by employing the I2-mediated deprotection and intramolecular ketal formation tandem reaction in the presence of NaHCO3 in MeCN. Our work provided flexible and practical approaches to synthesize and derive the 3,5,7-trisubstituted 6,8-dioxabicyclo [3.2.1] octane based analogs to search for new structure HIV-1 integrase inhibitors.

Graphical abstractThe marine natural product cyclodidemniserinol trisulfate was dissected into four fragments, which have been successfully synthesized herein. And by employing our established methodology, i.e., I2-mediated deprotection and intramolecular ketal formation tandem reaction, the coupling of fragment A and B proceeded smoothly to afford the key skeleton C5-C30 subunit of this natural product.Download full-size image