Yamaguchi macrolactonization 16- member

TE domain is able to catalyze the macrocyclization of oo-hydroxy fatty acid ethyl esters to afford 17- to 28-membered lactones [35]. One would hope that in the future a rather general TE domain will be identified or optimized via directed evolution, which could compete with the chemical Yamaguchi macrolactonization. 

The resulting ring size (44- vs 46- membered) was simply controlled by the macrolactonization conditions employed without differential C2i and C23 hydroxyl groups protection. Hydrolysis of the terminal methyl ester in 185 gave the acid 188 which selectively esterified, under Yamaguchi conditions [172], the C21 hydroxyl group of the diol 189 obtained by removal of the silylene group in 185. A 2 1 mixture of the desired C21... 

Chapter Synthesis of 12- to 16-Membered-Ring Lactones is dedicated to the synthesis of 12- to 16-membered ring lactones. In this chapter, M. Kalesse and M. Cordes present an overview of the macrocyclization of seco-acids as well as new effective procedures to access 12- to 16-membered ring lactones such as ringclosing metatheses of alkynes and olefins. The authors also report the use of ketene sources and benzodioxinones to produce macrocyclic lactones. Nitrile oxide-olefin cycloaddition, intramolecular C-H oxidative macrolactonization, and Yamaguchi and Mukaiyama macrocyclization as well as macrolactonization via thioester or using phosphorus reagents are described. 

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