Synthesis and Biological Evaluation of (2<i>S</i>,2′<i>S</i>)-Lomaiviticin A

Kaneko, Miho; Li, Zhenwu; Burk, Matthew T.; Colis, Laureen; Herzon, Seth B.

doi:10.1021/jacs.0c11960

Cited by 11 publications

(5 citation statements)

References 43 publications

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“…These compounds show complex stereochemistry, which is crucial to their biological activities. 108 So far, the total chemical synthesis of lomaivicitins has still not been conquered. Very recently, Herzon and coworkers carried out microED studies and successfully revised the structure of lomaivicitins, and especially identified the dimerized C-C bridge is located at C5, instead of C6 (Fig.…”

Section: Chemical Synthesis Of Cremeomycin and Kinamycin And Hydrazid...mentioning

confidence: 99%

Synthetic and biosynthetic routes to nitrogen–nitrogen bonds

Niikura

et al. 2022

Chem. Soc. Rev.

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Section: Chemical Synthesis Of Cremeomycin and Kinamycin And Hydrazid...mentioning

confidence: 99%

Synthetic and biosynthetic routes to nitrogen–nitrogen bonds

Niikura

et al. 2022

Chem. Soc. Rev.

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“…Of note, lomaiviticin A contains two diazotetrahydrobenzo[ b ]fluorene (diazofluorene) residues and four deoxyglycosides, two of which are β-linked, and a single carbon–carbon bond linking each half of the molecule. Due to its potent biological activity (low nM half-maximal inhibitory potencies (IC 50 s) against cultured human cancer cell lines), unique mechanism of action (induction of DNA double-strand breaks (DSBs)), and complex structure, the total synthesis of structure 1 was pursued for over 20 years . Despite these extensive efforts, there had not been a complete synthetic route to 1 or single-crystal X-ray analysis of any natural isolate, leaving the original assignment untested.…”

Section: Introductionmentioning

confidence: 91%

Stereocontrolled Synthesis of the Fully Glycosylated Monomeric Unit of Lomaiviticin A

DiBello

Wang

et al. 2022

J. Am. Chem. Soc.

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We describe a stereocontrolled synthesis of 3, the fully glycosylated monomeric unit of the dimeric cytotoxic bacterial metabolite (−)-lomaiviticin A (2). A novel strategy involving convergent, site- and stereoselective coupling of the β,γ-unsaturated ketone 6 and the naphthyl bromide 7 (92%, 15:1 diastereomeric ratio (dr)), followed by radical-based annulation and silyl ether cleavage, provided the tetracycle 5 (57% overall), which contains the carbon skeleton of the aglycon of 3. The β-linked 2,4,6-trideoxy-4-aminoglycoside l-pyrrolosamine was installed in 73% yield and with 15:1 β:α selectivity using a modified Koenigs–Knorr glycosylation. The diazo substituent was introduced via direct diazo transfer to an electron-rich benzoindene (4 → 27). The α-linked 2,6-dideoxyglycoside l-oleandrose was introduced by gold-catalyzed activation of an o-alkynyl glycosylbenzoate (75%, >20:1 α:β selectivity). A carefully orchestrated endgame sequence then provided efficient access to 3. Cell viability studies indicated that monomer 3 is not cytotoxic at concentrations up to 1 μM, providing conclusive evidence that the dimeric structure of (−)-lomaiviticin A (2) is required for cytotoxic effects. The preparation of 3 provides a foundation to complete the synthesis of (−)-lomaiviticin A (2) itself.

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“…Fluorene is a common core structure of functional materials − and biologically active pharmaceuticals. ,,− Recently, the Wen group has presented a palladium-catalyzed approach for synthesis of substituted fluorenes 83 via sequence Mizoroki–Heck/reductive Heck domino reactions between cyclic diaryliodoniums 81 and terminal alkenes 82 in the presence of Et 3 N/HCOONa as base/reducing agents (Scheme ). Mechanistically, palladium species coordinate with cyclic diaryliodoniums 81 , and subsequent insertion into alkenes followed by β-H elimination process generates a key intermediate int11 .…”

Section: Synthetic Applications Of Cyclic Aryliodoniumsmentioning

confidence: 99%

Recent Progress in Cyclic Aryliodonium Chemistry: Syntheses and Applications

et al. 2023

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Hypervalent aryliodoumiums are intensively investigated as arylating agents. They are excellent surrogates to aryl halides, and moreover they exhibit better reactivity, which allows the corresponding arylation reactions to be performed under mild conditions. In the past decades, acyclic aryliodoniums are widely explored as arylation agents. However, the unmet need for acyclic aryliodoniums is the improvement of their notoriously low reaction economy because the coproduced aryl iodides during the arylation are often wasted. Cyclic aryliodoniums have their intrinsic advantage in terms of reaction economy, and they have started to receive considerable attention due to their valuable synthetic applications to initiate cascade reactions, which can enable the construction of complex structures, including polycycles with potential pharmaceutical and functional properties. Here, we are summarizing the recent advances made in the research field of cyclic aryliodoniums, including the nascent design of aryliodonium species and their synthetic applications. First, the general preparation of typical diphenyl iodoniums is described, followed by the construction of heterocyclic iodoniums and monoaryl iodoniums. Then, the initiated arylations coupled with subsequent domino reactions are summarized to construct polycycles. Meanwhile, the advances in cyclic aryliodoniums for building biaryls including axial atropisomers are discussed in a systematic manner. Finally, a very recent advance of cyclic aryliodoniums employed as halogen-bonding organocatalysts is described.

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

Cited by 11 publications

References 43 publications

Synthetic and biosynthetic routes to nitrogen–nitrogen bonds

Synthetic and biosynthetic routes to nitrogen–nitrogen bonds

Stereocontrolled Synthesis of the Fully Glycosylated Monomeric Unit of Lomaiviticin A

Recent Progress in Cyclic Aryliodonium Chemistry: Syntheses and Applications

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