Modular Total Synthesis of iso-Archazolids and Archazologs

Full details on the design, development, and successful implementation of suitable synthetic strategies directed toward the total synthesis of iso-archazolids and archazologs are reported. Both a biomimetic and a multistep total synthesis of iso-archazolid B, the most potent and least abundant archazolid, are described. The bioinspired conversion from archazolid B was realized by a high-yielding 1,8-Diazabicyclo[5.4.0]undec-7-ene catalyzed one-step double-bond shift. A highly stereoselective total synthesis was accomplished in 25 steps, involving a sequence of highly stereoselective aldol reactions, an efficient aldol condensation to forge two elaborate fragments, and a challenging ring-closing metathesis macrocyclization with an unusual Stewart-Grubbs catalyst. These strategies proved to be generally useful and could be successfully implemented for the preparation of three novel iso-archazolids as well as five novel archazologs, lacking the thiazole side chain. A wide variety of further archazolids and archazologs may now be targeted for exploration of the promising anticancer potential of these polyketide macrolides.

Automated summary

The study details the full synthesis strategies for iso-archazolids and archazologs, including biomimetic conversion and multi-step synthesis. Through a series of reaction steps, the total synthesis of these potentially anticancer compounds was successfully accomplished.