Synthesis of the bis(cyclohexenone) core of (−)-lomaiviticin A

Abstract

<p>(−)-Lomaiviticin A is a cytotoxic, tetraglycosylated, <italic>C</italic>₂-symmetric bacterial metabolite. A synthesis of the dimeric core of lomaiviticin containing two carbohydrate residues is reported</p>

Synthesis and Biological Evaluation of (2S,2′S)-Lomaiviticin A

“…We reported a synthesis of (−)-lomaiviticin aglycon ( 3 ) that proceeded via the stereoselective oxidative coupling of two monomeric diazofluorenes to form the conjoining carbon–carbon bond (blue in 1 – 4 ). , Here we describe the application of this strategy to glycosylated monomeric diazofluorenes, ultimately providing access to (2 S ,2′ S )-lomaiviticin A ( 4 ), an unnatural diastereomer of (−)-lomaiviticin A ( 1 ) . (2 S ,2′ S )-Lomaiviticin A ( 4 ) is nontoxic at concentrations where (−)-lomaiviticin A ( 1 ) induces extensive cell kill and does not damage DNA in vitro or in tissue culture.…”

Total Synthesis of the Monomeric Unit of Lomaiviticin A

“…We have recently reported the total synthesis and full structural elucidation of namenamicin ( 1 ) . The rather intimidating molecular structures of lomaiviticin A ( 2 ) and its sibling, lomaiviticin B ( 3 ), however, present unprecedented synthetic challenges, although a number of important advances have been reported toward their total synthesis. , Furthermore, the total synthesis of kinamycins C ( 5 ), F ( 6 ), and J ( 7 ; monomeric relatives of lomaiviticins A and B, Figure ) have been accomplished. , Although related to the previously synthesized kinamycins C ( 5 ), F ( 6 ), and J ( 7 ), monolomaiviticin A ( 4 ), a possibly naturally occurring molecule not yet discovered, with its two unusual glycosidic bonds constitutes a novel and challenging synthetic target. Herein, we report the total synthesis of fully glycosylated monolomaiviticin A ( 4 , Figure ) as a prelude to the total synthesis of the naturally occurring lomaiviticins A ( 2 ) and B ( 3 ).…”