Practical synthesis of phthalascidin and zalypsis antitumor agents

The first total synthesis of zalypsis and the practical synthesis of phthalascidin (Pt-650) are achieved through the Pictet-Spengler cyclization coupling strategy. The direct iodination of the primary alcohol in trihydroxyl intermediate 26 followed by S(N)2 reaction with potassium phthalimide is employed to rapidly introduce the required amino functionality at C-22 on the pentacyclic framework. By the approaches, the two antitumor agents can be obtained from sesamol or N-Cbz-L-tyrosine with ca. 8%-10% overall yield. (C) 2021 Elsevier Ltd. All rights reserved.