The total synthesis of (--)-lemonomycin.

The first total synthesis of the novel glycosylated tetrahydroisoquinoline antitumor antibiotic (-)-lemonomycin has been accomplished (15 steps from 9). The highly convergent synthesis relies on a key asymmetric dipolar cycloaddition to set the stereochemistry of the aglycone core, a Suzuki fragment coupling to connect the diazabicycle to the aryl subunit, and a stereoselective Pictet-Spengler reaction that incorporates the aminoglycoside subunit directly into the core structure without the need for late-stage glycosylation or protecting group manipulations. The novel aminoglycoside was prepared using a highly diastereoselective Felkin-controlled acetate aldol addition reaction to a threonine-derived ketone.