The Structure of Amicetin

Stevens, Calvin L.; Nagarajan, K.; Haskell, Theodore H.

doi:10.1021/jo01056a006

Cited by 74 publications

(30 citation statements)

References 1 publication

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“…Reduction of (95) with sodium borohydride gave methyl 3,4-di-0acetyl-2,6-dideoxy-a-~-arab~no-hexopyranoside (97) 52 which was saponified to give the alcohol (98).52-55 Selective reaction with 9-toluenesulphonyl chloride afforded the 3-$-toluenesulphonate (99) 56 which on treatment with sodium azide gave a moderate yield of the azide (100) Reductive formylation of (100) gave methyl 2,3,6-t rideoxy-3-dimet hylamino-a-L-ribo-hexopyraposide (methyl L-megosaminide) (37) which was identical with the natural material. In a similar manner the panomer (101) 52 prepared by sodium borohydride reduction of (96) was converted into alcohol (102) 52954 which was then selectively reacted with $-toluenesulphonyl chloride to give (103).54 The latter was converted into the azide (104) 54*57 which on reductive formylation gave methyl p-L-megosaminide (38) which was identical with the natural sample.…”

Section: And Discussionmentioning

confidence: 99%

The megalomicins. Part 7. A structural revision by carbon-13 nuclear magnetic resonance and X-ray crystallography. Synthesis and conformational analysis of 3-dimethylamino- and 3-azido-D- and -L-hexopyranosides, and the crystal structure of 4″-O-(4-lodobenzoyl)megalomicin A

Bartner¹,

Boxler²,

Brambilla³

et al. 1979

J. Chem. Soc., Perkin Trans. 1

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An X-ray crystallographic study on 4"-0-(4-iodobenzoyl)megalomicin A has led to the revision of the structures of the megalomicins and the XK-41 antibiotics. Crystals are orthorhombic, space groupP2,2,2, with a = 12.669(2), b = 19.501 (6), c = 25.741 (9) A, and Z = 4. The structure was solved by the heavy-atom technique, and 1 812 observed reflections led to a final R of 0.095. The novel amino-sugar previously thought to be D-rhodosamine has been shown to have the L-configuration and is therefore renamed L-megosamine. It has also been shown to be glycosidically attached to the tertiary 6-hydroxy group. The 13C n.m.r. and circular dichroism (c.d.) parameters of these macrolides are described. The syntheses of methyl aand P-D-rhodosaminide, methyl aand P-D-megosaminide, methyl a-and 6-L-megosaminide, methyl a-and (3-D-angolosaminide, and methyl 2,3,6-trideoxy-3-(dimethylamino) -a-D-xylo-hexopyranoside are described and their conformations and 13C n.m.r. parameters are discussed. Methyl a-D-and -L-amicetoside, methyl a-D-and -L-cineruloside and other model 4-oxopyranosides and pyrans have been synthesized. Their c.d. properties have been determined and they have been shown to exhibit Anti-Octant behaviour.

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Section: And Discussionmentioning

confidence: 99%

The megalomicins. Part 7. A structural revision by carbon-13 nuclear magnetic resonance and X-ray crystallography. Synthesis and conformational analysis of 3-dimethylamino- and 3-azido-D- and -L-hexopyranosides, and the crystal structure of 4″-O-(4-lodobenzoyl)megalomicin A

Bartner¹,

Boxler²,

Brambilla³

et al. 1979

J. Chem. Soc., Perkin Trans. 1

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“…The chemical structure of amicetin was established in 1962 after extensive studies of its hydrolytic products (22,56) and was finally confirmed by crystallization studies (55). From various actinobacterial strains, a group of 10 amicetin analogues had been isolated, including bamicetin (compound 2) and plicacetin (compound 3) (31), norplicacetin (compound 4) (21), oxamicetin (42), SF2457 (37), oxyplicacetin (11), and cytosaminomycins A to D (30).…”

mentioning

confidence: 99%

Characterization of the Amicetin Biosynthesis Gene Cluster from Streptomyces vinaceusdrappus NRRL 2363 Implicates Two Alternative Strategies for Amide Bond Formation

Zhang

et al. 2012

Appl Environ Microbiol

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ABSTRACTAmicetin, an antibacterial and antiviral agent, belongs to a group of disaccharide nucleoside antibiotics featuring an α-(1→4)-glycoside bond in the disaccharide moiety. In this study, the amicetin biosynthesis gene cluster was cloned fromStreptomyces vinaceusdrappusNRRL 2363 and localized on a 37-kb contiguous DNA region. Heterologous expression of the amicetin biosynthesis gene cluster inStreptomyces lividansTK64 resulted in the production of amicetin and its analogues, thereby confirming the identity of theamigene cluster.In silicosequence analysis revealed that 21 genes were putatively involved in amicetin biosynthesis, including 3 for regulation and transportation, 10 for disaccharide biosynthesis, and 8 for the formation of the amicetin skeleton by the linkage of cytosine,p-aminobenzoic acid (PABA), and the terminal (+)-α-methylserine moieties. The inactivation of the benzoate coenzyme A (benzoate-CoA) ligase geneamiLand theN-acetyltransferase geneamiFled to two mutants that accumulated the same two compounds, cytosamine and 4-acetamido-3-hydroxybenzoic acid. These data indicated that AmiF functioned as an amide synthethase to link cytosine and PABA. The inactivation ofamiR, encoding an acyl-CoA-acyl carrier protein transacylase, resulted in the production of plicacetin and norplicacetin, indicating AmiR to be responsible for attachment of the terminal methylserine moiety to form another amide bond. These findings implicated two alternative strategies for amide bond formation in amicetin biosynthesis.

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“…30 The titration data revealed the pK a s for the two ionising residues to be 7.52 (tertiary amino N(I)) and 7.27 (primary amino NH 2 (VI)), which agree well with the data based on other methods reported in the literature. 3,4 Successful measurement of the pK a s also simultaneously provided additional evidence for the assignment of the proton resonances H1, H2, H19a and H19b, as described in the preceding section.…”

Section: Nmr Ph Titration Of Amicetinmentioning

confidence: 78%

“…1,2 Following fermentation growth and butanol solvent extraction, amicetin was isolated as a pure crystalline product and its chemical structure was solved by analysis of hydrolytic products. 3,4 Amicetin belongs to a family of nucleoside antibiotics containing a hexose-cytosine moiety ( Fig. 1) and functions as a peptidyl transferase RNA inhibitor by blocking protein biosynthesis within the cell.…”

Section: Introductionmentioning

confidence: 99%

NMR structure of the peptidyl transferase RNA inhibitor antibiotic amicetin

Shammas¹,

Donarski²,

Ramesh³

2006

Magnetic Reson in Chemistry

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In this communication, we report the solution state NMR structure determination of the peptidyl transferase RNA inhibitor antibiotic amicetin. We have successfully characterised the NMR spectrum of amicetin using a range of homo- and heteronuclear NMR techniques. Using experimental ROE-based distance and 1H--1H scalar coupling derived dihedral angle geometrical constraints as input into the three-dimensional structure determination protocol, we have generated an energy-minimised average structure of the antibiotic. Amicetin adopts a stable well-folded conformation in solution, mediated by a network of hydrogen bonds caused by proton donor and acceptor groups at either end of the molecule. The NMR structure of amicetin shows that the cytosine moiety occupies the critical turn position within the fold, which may be structurally significant for interaction with peptidyl transferase ribosomal RNA. The structure is distinctly different from the published X-ray crystal structure of amicetin in which it adopts a linear, extended chain-like conformation with a number of intermolecular hydrogen bonds. In addition to structure, we have probed the dynamics of amicetin in solution and have observed retarded exchange of the amide proton involved in folding. We have also characterised the ionisation properties of amicetin by carrying out NMR pH titration and measuring the pKa of the primary and tertiary amino groups, 7.27 and 7.52, respectively, which are in agreement with the reported values in literature. Solving the NMR structure of amicetin provides a valuable opportunity to determine the structure of its complex with RNA in solution state.

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The Structure of Amicetin

Cited by 74 publications

References 1 publication

The megalomicins. Part 7. A structural revision by carbon-13 nuclear magnetic resonance and X-ray crystallography. Synthesis and conformational analysis of 3-dimethylamino- and 3-azido-D- and -L-hexopyranosides, and the crystal structure of 4″-O-(4-lodobenzoyl)megalomicin A

The megalomicins. Part 7. A structural revision by carbon-13 nuclear magnetic resonance and X-ray crystallography. Synthesis and conformational analysis of 3-dimethylamino- and 3-azido-D- and -L-hexopyranosides, and the crystal structure of 4″-O-(4-lodobenzoyl)megalomicin A

Characterization of the Amicetin Biosynthesis Gene Cluster from Streptomyces vinaceusdrappus NRRL 2363 Implicates Two Alternative Strategies for Amide Bond Formation

NMR structure of the peptidyl transferase RNA inhibitor antibiotic amicetin

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