Group for Nucleotide Synthesis Summary: Allyloxycarbonyl (AOC) is excellent for the protection of sugar hydroxyls and amino and imide moieties of nucleoside bases. The deblocking is easily performed by brief treatment with a palladium catalyst and a variety of nucleophiles at room temperature.

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An improved asymmetric synthesis of renin inhibitor DS-8108b (1) is described. This compound consists of three intermediates: 4-aminoadamantan-1-ol, ketopiperazine, and chiral lactone which contains three stereogenic centers. Especially, the chiral lactone is a key intermediate, and development of a scalable synthetic method was required, considering the quality, speed, and manufacturing cost. We established a scalable synthetic method of 1 from 4,6-O-benzylidene-d-glucose for early clinical studies. Furthermore, a highly efficient synthetic route of the chiral lactone for manufacturing was also successfully developed from n-butyryl chloride via Evans stereoselective alkylation, followed by stereoselective bromolactonization. In addition, a unique and highly efficient conversion protocol was developed from α-bromo-N-(2-nitrobenzenesulfonyl)amide to apparent rearranged diamine derivatives with a sequential aziridination–substitution reaction in one-pot.