Asymmetric Total Synthesis of the Epoxykinamycin FL‐120 B′

Abstract

Turn up the heat: An asymmetric total synthesis of the epoxykinamycin FL-120B’ is reported. The synthesis establishes a route to epoxide-containing diazobenzofluorenes which could potentially serve as monomers to the dimeric lomaiviticins. Key steps include Sharpless asymmetric epoxidation, Stille coupling, and intramolecular Friedel-Crafts acylation of atropisomeric carboxylic acids at elevated temperatures to construct the FL-120B’ core structure.

Multigram synthesis of 1- O -acetyl-3- O -(4-methoxybenzyl)-4- N -(9-fluorenylmethoxycarbonyl)-4- N -methyl- l -pyrrolosamine

“…Several groups have initiated synthetic studies toward 1 and 2 . 5 Our laboratory reported a synthesis of (–)-lomaiviticin aglycon ( 3 ). 5i We also reported a strategy to prepare N , N -dimethyl- O -allyl-D-pyrrolosamine ( 5 ) and O -allyl-L-oleandrose ( 6 ) in three steps from ethyl (2 E ,4 R ,5 R )-4,5-epoxy-2-hexenoate ( 4 ) and ethyl (2 E ,4 S ,5 S )-4,5-epoxy-2-hexenoate ( ent- 4 ), respectively (Scheme 1).…”

“…5 Our laboratory reported a synthesis of (–)-lomaiviticin aglycon ( 3 ). 5i We also reported a strategy to prepare N , N -dimethyl- O -allyl-D-pyrrolosamine ( 5 ) and O -allyl-L-oleandrose ( 6 ) in three steps from ethyl (2 E ,4 R ,5 R )-4,5-epoxy-2-hexenoate ( 4 ) and ethyl (2 E ,4 S ,5 S )-4,5-epoxy-2-hexenoate ( ent- 4 ), respectively (Scheme 1). 5e The epoxides 4 and ent -4 were prepared in 41% yield and 96% ee by Shi epoxidation of ethyl sorbate, as previously described.…”

“…5i We also reported a strategy to prepare N , N -dimethyl- O -allyl-D-pyrrolosamine ( 5 ) and O -allyl-L-oleandrose ( 6 ) in three steps from ethyl (2 E ,4 R ,5 R )-4,5-epoxy-2-hexenoate ( 4 ) and ethyl (2 E ,4 S ,5 S )-4,5-epoxy-2-hexenoate ( ent- 4 ), respectively (Scheme 1). 5e The epoxides 4 and ent -4 were prepared in 41% yield and 96% ee by Shi epoxidation of ethyl sorbate, as previously described. 6 Distinct strategies to prepare protected forms of the aminosugar residues of 1 and 2 have also been reported by the Shair laboratory.…”

“…6 Distinct strategies to prepare protected forms of the aminosugar residues of 1 and 2 have also been reported by the Shair laboratory. 5c,5h …”

Studies toward the Synthesis of the Epoxykinamycin FL-120B′: Discovery of a Decarbonylative Photocyclization

“…3 In 2006 and 2011, our laboratory reported the total syntheses of kinamycin C and FL-120B', respectively. 4 Our approach to 1 and 2 involved elaboration of a benzofluorenone intermediate 3 which was accessed from a trifluoroacetic anhydride (TFAA)-mediated intramolecular Friedel-Crafts cyclization of carboxylic acid precursor 4 . During our studies toward the synthesis of FL-120B', an alternative cyclization involving intramolecular photoacylation of an aldehyde substrate containing a naphthoquinone chromophore was also explored.…”