Mycinolide synthesis

The Hoffmann mycinolide synthesis is based on the coupling of the Ci-Cio (227) and Cn-Cu (232) segments. The configuration of the former segment 227... 

Concerning Lewis acids, a catalytic amount of MesSil or MesSiOTf, as well as a stoichiometric amount of TiC104 or BF3-Et20, is effective. The favorable choice of Lewis acids with respect to the substitution pattern of the substrates has been reported. This methodology has been successfully utilized in the total synthesis of natural products which include avenaciolide and mycinolide IV. ... 

A more complex hydroxy acid is lactonized in a synthesis of (9S)-9-dihydroerythronolide A, albeit in low yield (equation 128). By acid treatment (356) is deprotected to give the desired target molecule. The presence of jp -centers in the seco-acid obviously facilitates lactonization, as shown by the preparation of the mycinolide V precursor (357 equation 129). A mixed carbonate is used in the synthesis of the tylonolide precursor (358 equation 130). ° In general, DMAP catalysis is helpful in the ring closing step in most cases. 

Ditrich, K., Bube, T., Sttirmer, R., and Hoffmann, R.W., Total synthesis of mycinolide V, the aglycone of a macrolide antibiotic of the mycinamycin series, Angew. Chem., Int. Ed. Engl., 25, 1028, 1986. Hoffmann, R.W., and Ditrich, K., Total synthesis of mycinolide V, Liebigs Ann. Chem., 23, 1990. Ditrich, K., Total synthesis of methynolide. Liebigs Ann. Chem., 789, 1990. 

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