Stereocontrolled Asymmetric Total Synthesis of Protomycinolide IV

Stereocontrolled asymmetric total synthesis of protomycinolide IV (1) was achieved, based on the organo-aluminum-promoted stereospecific pinacol-type 1,2-rearrangement. Two chiral fragments, C(1)–C(9) and C(11)–(17) portions, were constructed from a common chiral starting material, (S)-ethyl lactate. High diastereoselectivity of the nucleophilic attack on the Me₃Si-bearing α-methyl-β,γ-unsaturated carbonyl compounds was fully utilized for establishing the chiral centers at C(5) and C(6) relative to C(4) and C(15) relative to C(14). For the stereocontrol of the Me substituent at C(8), two methods were newly devised: (i) thermodynamic equilibration of δ-lactone 16 and (ii) acid-catalyzed stereoselective cyclization of ketene dithioacetal possessing an internal hydroxyl group.