Synthesis of lemonose derivatives: methyl 4-amino-3-O,4-N-carbonyl-2,4,6-trideoxy-3-C-methyl-α-l-lyxo-pyranoside and its phenyl thioglycoside

Briegel, Ariane; Cummings, Adrienne; Smith, Garry R.; Doroski, Matthew; Boyko, Walter J.; Piro, Nicholas A.; Kassel, W. Scott; Giuliano, Robert M.

doi:10.1016/j.carres.2015.03.006

Cited by 7 publications

(4 citation statements)

References 43 publications

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“…For donor 16 , we would optimize our previously described de novo synthesis from d -threonine ( 17 ) as this approach proved inefficient for the preparation of large amounts of 16 . Our route drew inspiration from previous syntheses of d -lemonose − as well as related amino sugars d -AAT, l -kedarosamine, and d -callipeltose …”

Section: Resultsmentioning

confidence: 99%

Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids

et al. 2021

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The arimetamycin A glycan governs the compound’s cytotoxicity (IC 50 ). To study this branched, deoxy-amino disaccharide, we designed and synthesized a modified acyl donor that underwent glycosylation with three anthracycline aglycones: steffimycinone, daunorubicinone, and doxorubicinone. The result of the approach was a synthesis of arimetamycin A and two novel hybrid anthracyclines. Each molecule exhibited enhanced cytotoxicity in comparison to the parent anthracyclines, steffimycin B, daunorubicin, and doxorubicin. An orienting mechanistic evaluation revealed that the daunorubicin hybrid inhibits the ability of human topoisomerase IIα to relax negatively and positively supercoiled DNA.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids

et al. 2021

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“…The second subcluster (sip6, sip7, sip8, sip10, sip11, and sip13) might be involved in the biosynthesis of a N,N-dimethyl derivative of a monosaccharide which formally corresponds to a 3,5-diepimer of lemonose (the amino sugar contained in lemonomycin) (28,29) and which we propose to trivially name D-sipanose (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

Cooperative Involvement of Glycosyltransferases in the Transfer of Amino Sugars during the Biosynthesis of the Macrolactam Sipanmycin by Streptomyces sp. Strain CS149

Malmierca

Pérez-Victoria

Martín

et al. 2018

Appl Environ Microbiol

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Macrolactams comprise a family of natural compounds with important bioactivities, such as antibiotic, antifungal, and antiproliferative activities. Sipanmycins A and B are two novel members of this family, with two sugar moieties attached to the aglycon. In the related macrolactam vicenistatin, the sugar moiety has been proven to be essential for cytotoxicity. In this work, the gene cluster responsible for the biosynthesis of sipanmycins ( cluster) in sp. strain CS149 is described and the steps involved in the glycosylation of the final compounds unraveled. Also, the cooperation of two different glycosyltransferases in each glycosylation step is demonstrated. Additionally, the essential role of SipO2 as an auxiliary protein in the incorporation of the second deoxy sugar is addressed. In light of the results obtained by the generation of mutant strains and characterization of the cluster, a biosynthetic pathway for sipanmycins and the two deoxy sugars attached is proposed. Finally, the importance of the hydroxyl group at C-10 of the macrolactam ring and the sugar moieties for cytotoxicity and antibiotic activity of sipanmycins is shown. The rapid emergence of infectious diseases and multiresistant pathogens has increased the necessity for new bioactive compounds; thus, novel strategies have to be developed to find them. Actinomycetes isolated in symbiosis with insects have attracted attention in recent years as producers of metabolites with important bioactivities. Sipanmycins are glycosylated macrolactams produced by sp. CS149, isolated from leaf-cutting ants, and show potent cytotoxic activity. Here, we characterize the cluster and propose a biosynthetic pathway for sipanmycins. As far as we know, it is the first time that the cooperation between two different glycosyltransferases is demonstrated to be strictly necessary for the incorporation of the same sugar. Also, a third protein with homology to P450 monooxygenases, SipO2, is shown to be essential in the second glycosylation step, forming a complex with the glycosyltransferase pair SipS9-SipS14.

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“…For its synthesis, it is necessary to have a deoxygenated precursor at the C-2′ position and this was successfully achieved via a thiocarbonyl imidazole 92 derivative and subsequent reduction with TTMSS (1.5 equiv) in anhydrous benzene and AIBN initiation with a 81% yield of the reduction product of 92 (Scheme ). Another successful example of deoxygenation in the sugar ring is the synthesis of colitose (i.e., 3,6-dideoxyhexose) thioglycoside 93 . The TTMSS (2 equiv), used in benzene at 80 °C with AIBN (15 mol %) as initiator, not only represented an improvement of the tin hydride toxicological problems but also revealed more effective with the possibility of scaling-up the synthesis on gram scale with 98% yield of reduction product 93 .…”

Section: Reduction Of Functional Groupsmentioning

confidence: 99%

Thirty Years of (TMS)₃SiH: A Milestone in Radical-Based Synthetic Chemistry

et al. 2018

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This review is an update on tris(trimethylsilyl)silane, TTMSS, in organic chemistry, focusing on the advancements of the past decade. The overview includes a wide range of chemical processes and synthetic strategies under different experimental conditions, including functional group insertion and transformations, as well as preparation of complex molecules, natural products, polymers, surfaces, and new materials. These results reveal how TTMSS has matured over the past 30 years, and they further establish its value as a free radical reagent with widespread academic and industrial applications.

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Synthesis of lemonose derivatives: methyl 4-amino-3-O,4-N-carbonyl-2,4,6-trideoxy-3-C-methyl-α-l-lyxo-pyranoside and its phenyl thioglycoside

Cited by 7 publications

References 43 publications

Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids

Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids

Cooperative Involvement of Glycosyltransferases in the Transfer of Amino Sugars during the Biosynthesis of the Macrolactam Sipanmycin by Streptomyces sp. Strain CS149

Thirty Years of (TMS)₃SiH: A Milestone in Radical-Based Synthetic Chemistry

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Synthesis of lemonose derivatives: methyl 4-amino-3-O,4-N-carbonyl-2,4,6-trideoxy-3-C-methyl-α-l-lyxo-pyranoside and its phenyl thioglycoside

Cited by 7 publications

References 43 publications

Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids

Synthesis and Cytotoxic Evaluation of Arimetamycin A and Its Daunorubicin and Doxorubicin Hybrids

Cooperative Involvement of Glycosyltransferases in the Transfer of Amino Sugars during the Biosynthesis of the Macrolactam Sipanmycin by Streptomyces sp. Strain CS149

Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry

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Thirty Years of (TMS)₃SiH: A Milestone in Radical-Based Synthetic Chemistry