Macrolactonization protocols

A key feature of most macrolactonization protocols is enhancement of the acyl group. 

Extension of the traditional Yamaguchi/Corey-Nicolaou/Keck macrolactonization protocols (see Scheme 2.1) [5] to catalytic variants can address some of the drawbacks of classical methods. Mixed anhydrides can undergo cyclization with Lewis adds such as Sc,1i, Zr, and Hf [125,126].Trostetol. reported the use of ethoxyacetylene as a stoichiometric activating agent, installed via Ru catalysis [127], later applied to the synthesis of apicularen A (Scheme 2.67) [128]. 

Brady and Sanders (328) reported the synthesis of dynamic macrolactone libraries based on the thermodynamic transesterification/cyclization of easily accessible cholate monomers 8.117-8.119 (Fig. 8.56). The transesterification conditions were first studied with 8.117, and the mixture of potassium methoxide and a crown ether in toluene was found to be the best thermodynamic protocol. At 5 mM concentration of... 

R.S. Coleman and co-workers have developed a stereoselective synthesis of the 12-membered diene and triene lactones characteristic of the antitumor agent oximidines I and II, based on an intramolecular Castm-Stephens coupling. The effectiveness of this protocol rivals the efficiency of standard macrolactonization. The stereoselective reduction of the internai alkyne afforded the 12-membered ( ,Z)-diene lactone in good yield. 

In a remarkable experiment (scheme 5) S. F prepared diglycosidated seco acid 17 from 2 Martin and M. Yamashita [13] have parted via partial synthesis in ten steps and subjected with the accepted philosophy of erythromycin it to Yamaguchi s macrolactonization conditi-synthesis, namely to perform first the lactoni- ons. However, this protocol afforded only zation and then the glycosidation. They minor amounts of the desired macrolide 18,... 

The coupling of 77 and 84 was performed via the Julia-Julia olefination [50] to construct the ( )-olefin 85 EjZ => 20) at the C14-C15 bond. This approach is slightly more efficient than that of the Kocienski-Julia protocol in the case of Lee s synthesis. As a macrocyclization, the intramolecular Horner-Emmons reaction was adopted, because macrolactonization of the hydroxy (E, )-dienylcarboxylic acid was difficult. The phosphonate 86, derived from 85, was exposed to K2CO3 and 18-crown-6 [51-53] to provide the macrolactone 87 in good yield. Finally, the side chain was introduced via the Wittig reaction like Lee s method, and the second total synthesis was accomplished. 

Recently, Shishido has achieved the third total synthesis of (+)-lasonolide A, and their synthetic strategy was based on the introduction of the side chain via Lee s protocol, the successful Yamaguchi macrolactonization, and the... 

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