Macrocyclic natural products olefins

In the ring-closing metathesis reaction (RCM), a diene is allowed to undergo intramolecular olefin metathesis to give a cyclic alkene and ethylene the latter is removed to drive the equilibrium forward. The RCM has quickly been adopted as a premier method for preparing macrocyclic natural products. 

In term of diversity-oriented strategies, multicomponent reactions (MCR) represent an attractive and rapid access to libraries of macrocycles inspired by biologically active natural products. Combined with Passerini and Ugi reactions, M-RCM has already shown promising synthetic potential, as illustrated by the pioneering work of Domling and coworkers [46]. Condensation of isocyanide 69 with carboxylic acid 70 in the presence of paraformaldehyde leads to bis-olefin 71, which is subsequently submitted to RCM in the presence of G1 and titanium isopropoxide to give the 22-membered macrocycle 72 (Scheme 2.27). 

The first total synthesis of racemic indolizomycin was accomplished by S.J. Danishefsky et a. The natural product s trienyl side chain was elaborated using the classical J-L olefination. The macrocyclic a, 3-unsaturated aldehyde was treated with an ( )-allylic lithiated sulfone to give epimeric acetoxy sulfones upon acetylation. The mixture of epimers was exposed to excess sodium amalgam in methanol to afford the desired ( , , ) triene stereospecifically. 

Both TIN and TTA [Tl(OAc)3] have been known to act as electrophiles toward olefinic double bonds, enolizable ketones and nitrogen-containing compounds to afford a variety of natural products or their synthons. As already shown in Scheme 162, TIN was applied to phenolic oxidation by Yamamura and Nishiyama . In particular, this method which consists of TIN oxidation in MeOH followed by Zn reduction in AcOH is effective for the construction of macrocyclic diaryl ethers from the corresponding open-ring precusors, which are required to possess two o,o -dihalophenol moieties. 

The epothilones comprise an important set of natural products that were discovered at a time contemporary with the development of ring-closing olefin metathesis. These materials are 16-membered ring compounds containing an alkene in the macrocycle or an epoxide that can be generated from the alkene. A conventional retrosyntlietic analysis... 

Natural Acetylenic and Olefinic Compounds, excluding Marine Natural Products Acyclic Terpenoids Insect Pheromones and Related Behaviour-modifying Chemicals Olefinic Microbial Metabolites, including Macrocyclic Compounds Prostaglandins Fatty Acids and Glycerides Polar Lipids. 

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