Total Synthesis of (+)-Sinefungin

Abstract

Sinefungin (1) a nucleoside antibiotic isolated from Streptomyces has been synthesized from D-ribose. Both the C-6 and C-9 stereogenic centers were constructed by efficient asymmetric syntheses. The C-6 amine stereochemistry was set by a highly diastereoselective allylation (>99% de) of a (1S,2R)-1-amino-2-indanol-derived oxazolidinone 9 followed by a Curtius rearrangement of 11 to 12. The C-9 amino acid stereochemistry of sinefungin (1) was established by a rhodium chiral bisphosphine-catalyzed asymmetric hydrogenation of an alpha-(acylamino)acrylate derivative. The anomeric adenosylation of the mixture of anomeric acetates 20 in the presence of C-6 urethane NH was found to be extremely difficult. Conversion of the C-6 urethane NH as its N-benzyl derivative 21 was necessary prior to the adenosylation reaction. Successful adenosylation was effectively carried out by Vorbrüggen's protocol utilizing persilylated N(6)-benzoyladenine and trimethylsilyl triflate.