Modular Total Synthesis of -Archazolids and Archazologs.

Full details on the design, development, and successful implementation of suitable synthetic strategies directed toward the total synthesis of -archazolids and archazologs are reported. Both a biomimetic and a multistep total synthesis of -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.

Design, Synthesis and Biological Evaluation of Highly Potent Simplified Archazolids.

The archazolids are potent antiproliferative compounds that have recently emerged as a novel class of promising anticancer agents. Their complex macrolide structures and scarce natural supply make the development of more readily available analogues highly important. Herein, we report the design, synthesis and biological evaluation of four simplified and partially saturated archazolid derivatives.

Synthesis of Novel Potent Archazolids: Pharmacology of an Emerging Class of Anticancer Drugs.

Vacuolar type ATPase (V-ATPase) has recently emerged as a promising novel anticancer target based on extensive and studies with archazolids, complex polyketide macrolides, which present the most potent V-ATPase inhibitors known to date. Herein, we report a biomimetic, one-step preparation of archazolid F, the most potent and least abundant archazolid, the design and synthesis of five novel, carefully selected archazolid analogues, and the biological evaluation of these antiproliferative agents, leading to the discovery of a very potent but profoundly simplified archazolid analogue. Furthermore, the first general biological profiling of the archazolids against a broad range of more than 100 therapeutically relevant targets is reported, leading to the discovery of novel and important targets.