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.
Ashley
Eric R
ER
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Cruz
Ernest G
EG
Stoltz
Brian M
BM
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D003500:Cyclization; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis*
D000903:Antibiotics, Antineoplastic; D044005:Tetrahydroisoquinolines; C481507:lemonomycin