Total Synthesis of TAN-1057 A/B, a New Dipeptide Antibiotic fromFlexibacter sp. PK-74

Соколов, В. В.; Kozhushkov, Sergei I.; Nikolskaya, Sofia; Belov, Vladimir N.; Es‐Sayed, Mazen; Meijere, Armin de

doi:10.1002/(sici)1099-0690(199805)1998:5<777::aid-ejoc777>3.0.co;2-w

Cited by 32 publications

(19 citation statements)

References 19 publications

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“…[14] Spectroscopic data: 1 H NMR (400 MHz, DMSO-d6) δ 8.30 (bs, 2H), 7.35–7.29 (m, 5H), 5.10–5.03 (m, 2H) 4.73 (t, 1H, J=6.89Hz), 3.63 (s, 3H) 3.32–3.26 (m, 2H), 2.91 (s, 3H); 13 C NMR (400 MHz, DMSO-d6) δ 169.74, 156.68, 137.17, 129.09, 128.41, 128.10, 67.55, 59.22, 53.15, 38.11, 34.85; MS (ESI positive ion mode) exact mass calculated for C 13 H 18 N 2 O 4 : 266.13, found (M+H) + : 267.09.…”

Section: Methodsmentioning

confidence: 99%

Targeting a Regulatory Element in Human Thymidylate Synthase mRNA

et al. 2012

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Thymidylate synthase (TS) is a key enzyme in the biosynthesis of thymidine. TS inhibitors, which are used in cancer chemotherapy, suffer from resistance development in tumors through upregulation of TS expression. Autoregulatory translation control has been implicated with TS overexpression. TS binding at its own mRNA, which leads to sequestration of the start codon, is abolished when the enzyme forms an inhibitor complex, thereby relieving translation suppression. We have used the protein binding site from the TS mRNA in the context of a bicistronic expression system to validate targeting the regulatory motif with stabilizing ligands that prevent ribosomal initiation. Stabilization of the RNA by mutations, which were studied as surrogates of ligand binding, suppresses translation of the TS protein. Compounds that stabilize the TS binding RNA motif and thereby inhibit ribosomal initiation might be used in combination with existing TS enzyme-targeting drugs to overcome resistance development during chemotherapy.

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Section: Methodsmentioning

confidence: 99%

Targeting a Regulatory Element in Human Thymidylate Synthase mRNA

et al. 2012

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“…[334] The conversion of orthogonally protected arginine 438 into the homologue 439 [335] was used to prepare TAN 1057 (440), an antibiotic with strong activity against methicillin-resistant strains of Staphylococcus aureus (Scheme 53). [336] An approach to the peptide antibiotic (ϩ)-negamycin (443) has been reported which starts from 441 and proceeds by way of 442.…”

Section: Homologation Of α-Amino Acidsmentioning

confidence: 99%

100 Years of the Wolff Rearrangement

2002

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The conversion of α‐diazo ketones into ketenes, and products derived therefrom, was discovered by Wolff in 1902. Major applications of the Wolff rearrangement, such as the Arndt−Eistert reaction (homologation of carboxylic acids) and the ring contraction of cyclic ketones, have been with us for some while. Nevertheless, substantial progress has been made recently. The reaction mechanism has been explored by means of matrix isolation, time‐resolved spectroscopy, and computation. Full retention of configuration of the migrating group has been established by using enantioselective chromatography. The Arndt−Eistert reaction has witnessed a renaissance in the field of natural products, in particular β‐amino acids and β‐peptides. Ring‐contracting Wolff rearrangements and ketene cycloadditions have been applied in syntheses of increasingly complex, biologically active target molecules. These accomplishments, as well as unsolved problems, are addressed in the present review. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

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“…The more‐convergent synthesis of de Meijere, Belov, and co‐workers (Scheme ) was published shortly after 324. The racemic asparagine derivative 137 was prepared through a Michael addition of methylamine to maleamide.…”

Section: Tetrahydropyrimidinone Antibioticsmentioning

confidence: 99%

“… De Meijere, Belov and co‐workers's synthesis of TAN‐1057A/B ( 127 / 128 ) 324. Reagents and conditions: a) PhCH 2 OCOCl, aq.…”

Section: Tetrahydropyrimidinone Antibioticsmentioning

confidence: 99%

Oligothiophene Isothiocyanates as Fluorescent Markers

Barbarella

2002

Chem. Eur. J.

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To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti‐infectives. Surprisingly, numerous “old” classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the “old fashioned” natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target‐finding tools from biology (reversed genomics) is one option for their revival.

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Total Synthesis of TAN-1057 A/B, a New Dipeptide Antibiotic fromFlexibacter sp. PK-74

Cited by 32 publications

References 19 publications

Targeting a Regulatory Element in Human Thymidylate Synthase mRNA

Targeting a Regulatory Element in Human Thymidylate Synthase mRNA

100 Years of the Wolff Rearrangement

Oligothiophene Isothiocyanates as Fluorescent Markers

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