Macrocyclic Drugs and Synthetic Methodologies toward Macrocycles
Open Access
Abstract
Macrocyclic scaffolds are commonly found in bioactive natural products and pharmaceutical molecules. So far, a large number of macrocyclic natural products have been isolated and synthesized. The construction of macrocycles is generally considered as a crucial and challenging step in the synthesis of macrocyclic natural products. Over the last several decades, numerous efforts have been undertaken toward the synthesis of complex naturally occurring macrocycles and great progresses have been made to advance the field of total synthesis. The commonly used synthetic methodologies toward macrocyclization include macrolactonization, macrolactamization, transition metal-catalyzed cross coupling, ring-closing metathesis, and click reaction, among others. Selected recent examples of macrocyclic synthesis of natural products and druglike macrocycles with significant biological relevance are highlighted in each class. The primary goal of this review is to summarize currently used macrocyclic drugs, highlight the therapeutic potential of this underexplored drug class and outline the general synthetic methodologies for the synthesis of macrocycles.Keywords
This publication has 241 references indexed in Scilit:
- Build/Couple/Pair Strategy for the Synthesis of Stereochemically Diverse Macrolactams via Head-to-Tail CyclizationACS Combinatorial Science, 2012
- Total Synthesis of (−)-4,8,10-Tridesmethyl TelithromycinThe Journal of Organic Chemistry, 2011
- Enantioselective Total Synthesis of (−)-Zampanolide, a Potent Microtubule-Stabilizing AgentOrganic Letters, 2011
- Total synthesis and structural revision of engelhardioneTetrahedron Letters, 2011
- Stereoselective synthesis of the decahydrofluorene core of the hirsutellonesTetrahedron Letters, 2011
- Synthesis of the Cytotrienin A Core via Metal Catalyzed C−C CouplingOrganic Letters, 2011
- Total Synthesis of Hirsutellone BAngewandte Chemie International Edition, 2009
- Skeletally Diverse Small Molecules Using a Build/Couple/Pair StrategyOrganic Letters, 2009
- A Rapid, Asymmetric Synthesis of the Decahydrofluorene Core of the HirsutellonesOrganic Letters, 2009
- Towards the Optimal Screening Collection: A Synthesis StrategyAngewandte Chemie International Edition, 2007