The landomycins constitute a unique group of the angucycline antibiotics, featuring a benz[a]anthraquinone aglycone with a dearomatized B ring and deoxyoligosaccharide chains of varied length attached at the C8-OH. These compounds show potent antitumor activities; the potency and mechanism of action varies along variation of the sugar residues. Chemical synthesis of landomycins had challenged chemists for many years; the major synthetic difficulties include: the vulnerability of the aglycon toward aromatization of the B ring in both acidic and basic conditions; the vulnerability of the di- and tri-deoxyglycosidic linkages toward cleavage/anomerization; formation of the thermodynamically unfavorable 2-deoxy-b-glycosidic linkages; attachment of a saccharide onto a poorly nucleophilic aglycon acceptor. This lecture reports 15-year experiences toward the total synthesis of landomycin A, the longest and the most potent antitumor congener of landomycins.
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