- Guanidyl modification of the 1-azabicyclo[3.1.0]hexane ring in ficellomycin essential for its biological activity
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The 1-azabicyclo[3.1.0]hexane ring is a key moiety in natural products for biological activities against bacteria, fungi, and tumor through DNA alkylation. Ficellomycin is a dipeptide that consists of l-valine and a non-proteinogenic amino acid with the 1-azabicyclo[3.1.0]hexane ring structure. Although the biosynthetic gene cluster of ficellomycin has been identified, the biosynthetic pathway currently remains unclear. We herein report the final stage of ficellomycin biosynthesis involving ring modifications and successive dipeptide formation. After the ring is formed, the hydroxy group of the ring is converted into the guanidyl unit by three enzymes, which include an aminotransferase with a novel inter ω-ω amino-transferring activity. In the last step, the resulting 1-azabicyclo[3.1.0]hexane ring-containing amino acid is connected with l-valine by an amino acid ligase to yield ficellomycin. The present study revealed a new machinery that expands the structural and biological diversities of natural products. This journal is
- Hasebe, Fumihito,Kurosawa, Sumire,Kuzuyama, Tomohisa,Matsuda, Kenichi,Nishiyama, Makoto,Shin-Ya, Kazuo,Shiraishi, Taro
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p. 5137 - 5144
(2020/07/23)
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- Synthesis of substituted N-(2′-nitrophenyl)pyrrolidine-2-carboxamides towards the design of proline-rich antimicrobial peptide mimics to eliminate bacterial resistance to antibiotics
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The treatment of diseases is under threat due to the increasing resistance of disease-causing bacteria to antibiotics. Likewise, free radical-induced oxidative stress has been implicated in several human disease conditions, such as cancer, stroke and diabetes. In the search for amino acid analogues with antibacterial and antioxidant properties as possible mimics of antimicrobial peptides, substituted N-(2′-nitrophenyl)pyrrolidine-2-carboxamides 4a–4k and N-(2′-nitrophenyl)piperidine-2-carboxamides 4l–4n have been synthesized via a two-step, one-pot amidation of the corresponding acids, using thionyl chloride with different amines in dichloromethane. The carboxamides were characterized by infrared and nuclear magnetic resonance spectroscopy, mass spectrometry and elemental analysis. Carboxamides 4a–4n were assayed against five Gram-positive and five Gram-negative bacterial strains using the broth micro-dilution procedure and compared to standard antibiotic drugs (streptomycin and nalidixic acid). 4b showed the highest antibacterial activity with a minimum inhibitory concentration (MIC) value of 15.6 μg/mL against Staphylococcus aureus. Pertinently, 4b and 4k are promising candidates for narrow-spectrum (Gram-positive) and broad-spectrum antibiotics, respectively. The antioxidant properties of the carboxamides were also evaluated using the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical cation. 4a and 4k recorded the lowest IC50 values of 1.22 × 10–3 mg/mL (with DPPH) and 1.45 × 10–4 mg/mL (with ABTS), respectively. Notably, 4k recorded about 2.5 times better antioxidant capacity than the positive controls – ascorbic acid and butylated hydroxyanisole. These results bode well for N-aryl carboxamides as good mimics and substitutes for antimicrobial peptides towards mitigating bacterial resistance to antibiotics as well as ameliorating oxidative stress-related diseases.
- Odusami, Jocelyn A.,Ikhile, Monisola I.,Izunobi, Josephat U.,Olasupo, Idris A.,Osunsanmi, Foluso O.,Opoku, Andrew R.,Fotsing, Marthe C.D.,Asekun, Olayinka T.,Familoni, Oluwole B.,Ndinteh, Derek T.
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- Iron- or Zinc-Mediated Synthetic Approach to Enantiopure Dihydroquinoxalinones
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A general and efficient synthesis of enantiopure dihydroquinoxalinones has been developed using naturally occurring amino acids as starting materials. The reductive cyclization of N-(o-nitroaryl)amino esters was performed by using iron and zinc metal under mild conditions in a water/ethyl acetate mixture. The corresponding dihydroquinoxalinones were obtained in moderate to high yields and high enantiomeric purity, among which 7 new compounds were unprecedented in the literature.
- Li, Dazhi,Ollevier, Thierry
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supporting information
p. 1273 - 1280
(2019/01/04)
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- V-PROU/NO, a prodrug of the nitric oxide donor, PROLI/NO
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The sensitivity to decomposition of the nitric oxide (NO) donor ion, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), complicates direct electrophilic substitution to form useful prodrug derivatives. A modified general synthetic approach involving 1-[2-(hydroxymethyl)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate ion (structure A, above) was used to prepare several PROLI/NO prodrugs including the previously Inaccessible O2vinyl derivative, V-PROLl/NO. Metabolism of V-PROLI/NO by liver microsomes enriched in human cytochrome P450 isoforms was demonstrated.
- Chakrapani, Harinath,Showalter, Brett M.,Kong, Li,Keefer, Larry K.,Saavedra, Joseph E.
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p. 3409 - 3412
(2008/02/12)
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- A novel method for the synthesis of chiral epoxides from styrene derivatives using chiral acids in presence of Pseudomonas lipase G6 [PSL G6] and hydrogen peroxide
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Chiral epoxidation of styrene and its derivatives was carried out using series of chiral acids and urea hydrogen peroxide (UHP) or aqueous hydrogen peroxide (50%) in two phases under the catalytic influence of immobilized Pseudomonas lipase G6 [PSL G6] at 25-55 °C. A moderate to good yield and enantioselectivities of chiral epoxides were obtained.
- Sarma, Kuladip,Bhati, Nishi,Borthakur, Naleen,Goswami, Amrit
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p. 8735 - 8741
(2008/02/09)
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- Synthesis of tri- and tetracyclic condensed quinoxalin-2-ones fused across the C-3 - N-4 bond
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We have studied the preparation of some fused quinoxalinones by Stevens rearrangement of a spiro-quinoxaline-derived ammonium ylide or by treatment of N-(2,4-dinitrophenyl)-and N-(2-nitrophenyl)imino acids with different reducing agents. We have reinvestigated and clarified some related processes found in the literature starting from imino acids derivatives. Additional reactions of the fused quinoxalinones, as well as the useful dehydrogenation/decarboxylation of some easily available 1-arylindoline-2-carboxylic acids to the corresponding 1-arylindoles, are also reported. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Chicharro, Roberto,De Castro, Sonia,Reino, Jose L.,Aran, Vicente J.
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p. 2314 - 2326
(2007/10/03)
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- Simple and efficient preparation of (R)- and (S)-enantiomers of α-carbon deuterium-labelled α-amino acids
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A procedure for the synthesis of (R)- and (S)-enantiomers of α-carbon deuterium-labelled α-amino acids, exemplified for (R)- and (S)-[2-2H1]-Leu is described. Starting from the respective (S)- or (R)-enantiomer or from the racemic mixture of an α-amino acid the selective proton exchange at the α-carbon is carried out by racemization via a Schiff base in monodeuterated acetic acid as solvent which serves as deuterium source. After N-protection the racemic mixture is liquid chromatographically separated into the individual (R)- and (S)-enantiomers on preparative scale employing a chiral anion exchanger based on carbamoylated quinine as chiral selector. After deprotection the enantiomerically pure products can be obtained in good yields.
- Mitulovi, Goran,Laemmerhofer, Michael,Maier,Lindner, Wolfgang
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p. 449 - 461
(2007/10/03)
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- 1,2,4-TRINITROBENZENE AS A THIOL REAGENT
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The 2,4-dinitrophenylation of thiol or amino group with 1,2,4-trinitrobenzene proceeded quantitatively at pH 8.5 and 30 deg C.The rate of S-dinitrophenylation was ca. 1E4 times faster than that of N-dinitrophenylation.So this reaction can be used for both the determination of thiol even in the presence of large excess amine and the specific modification of thiol in proteins.
- Takahashi, Seitaro,Kokubo, Masayuki,Satake, Kazuo
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p. 1445 - 1448
(2007/10/02)
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- Polycyclic Nitrogen Compounds. Part I. Synthesis of New Heterotricyclic Quinoxalinones with Bridgehead Nitrogen Atoms
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New tricyclic quinoxalinone skeletons with a fully-reduced ring 'C' -1,2,3,3a-tetrahydropyrroloquinoxalin-4-one (I-II) and 7,8,9,10-tetrahydropyridoquinoxalin-6-one (III-IV) derivatives were obtained by selective hydrogen transfer reductive cyclisation of N-(2-nitrophenyl)pyrrolidine-2-carboxylic acid esters and N-(2-nitrophenyl)piperidine-2-carboxylic acid esters (VIa,b and VIIIa,b), respectively.
- Adegoke, E. A.,Alo, Babajide I.,Ogunsulire, F. O.
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p. 1169 - 1172
(2007/10/02)
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