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A highly convergent total synthesis of (-)-bastimolide A (1), a polyhydroxy antimalarial macrolide, has been achieved via a longest linear sequence of twenty steps from commercially available glycidyl ethers. Type I Anion Relay Chemistry (ARC) coupling tactics enable rapid construction of the molecule's 1,5-polylol backbone. A late-stage B-alkyl Suzuki-Miyaura union and an Evans-modified Mukaiyama macrolactonization generate the forty-membered Z-α,β-unsaturated macrocyclic lactone., (© 2022 Wiley-VCH GmbH.)

The development of a concise total synthesis of (±)-phyllantidine (1), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen-oxygen (N-O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early-stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N-O bond cleavage, and the rapid assembly of the butenolide found in (1) via use of the Bestmann ylide., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)