Surugamides A–E, Cyclic Octapeptides with Four <scp>d</scp>-Amino Acid Residues, from a Marine Streptomyces sp.: LC–MS-Aided Inspection of Partial Hydrolysates for the Distinction of <scp>d</scp>- and <scp>l</scp>-Amino Acid Residues in the Sequence

Takada, Kentaro; Ninomiya, Akihiro; Naruse, Mitsuhide; Sun, Yi; Miyazaki, Masaru; Nogi, Yuichi; Okada, Shigeru; Matsunaga, Shigeki

doi:10.1021/jo400708u

Cited by 76 publications

(116 citation statements)

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“…This is further supported by the fact that D-allo-isoleucine has been found previously in natural products, 3 while secondary metabolites which feature either D-isoleucine, or its α-epimer (7), are relatively uncommon in the literature. 5 We therefore believed that the taumycin macrolide was more likely to feature one Land one D-allo-isoleucine (Figure 1).At the onset of our synthetic campaign, we believed that the prudent approach might be to first target aldehyde 3, a compound initially accessed by Kashman 2a via reductive ozonolysis of 1, as a means to address both the unknown …”

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The taumycin A macrocycle: Asymmetric total synthesis and revision of relative stereochemistry

Maio

2015

Planta Med

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The first asymmetric total synthesis and revision of the relative configuration of the 12-membered taumycin A macrocycle is described. Key to the success of this work was a novel α-keto ketene macrocyclization that provided an efficient means by which to access two diastereomers of the desired macrolide without the need to employ additional coupling agents or unnecessary oxidation state adjustments.T he symbiotic association of marine microorganisms with their host sponges continues to be an extraordinary source of hybrid polyketide/nonribosomal secondary metabolites that often possess unique structures in conjunction with interesting biological activity.1 Recently, taumycins A and B (1−2, Figure 1) were isolated by Kashman and co-workers, in extremely small amounts, from a Madagascar sponge of genus Fascaplysinopsis.2a Of particular note, taumycin A (1) was shown to inhibit UT-7 cell growth in the micromolar range, whereas taumycin B (2), which lacks the terminal oxazole moiety at C(12), is completely devoid of this activity.2a To date, extensive biological evaluation has not been performed on either metabolite, and the mechanism of action of 1 remains unknown. 2aThe relative configuration of the macrolide common to 1 and 2 was assigned using both detailed multidimensional NMR analyses and degradation studies (cf. 3); however, due to its remote location, the configuration about the side chain C(9) methyl remains undefined. As determined by Kashman, 2a,b the taumycin macrolide contains one L-and one D-isoleucine residue (Figure 1) which, in the absence of an X-ray quality crystal, made it difficult to establish absolute stereochemistry due to what was perceived to be potential ambiguity surrounding the correct sequence of amino acid subunits within the macrocycle.We were attracted to taumycin A as a synthetic target not only because of its biological profile but also due to the reported presence of enantiomeric isoleucine residues. A careful examination of the isolation report, however, revealed that there was no clear discussion on how the data collected guided the authors to distinguish between D-isoleucine and D-alloisoleucine (Figure 1). 3With this in mind, the relative stereochemistry as drawn by Kashman in the isolation report is somewhat unclear, as it does not adequately address the two stereocenters in each isoleucine residue (cf. Kashman vs. Expanded Stereochemistry, Figure 1). The presence of a D-amino acid is usually regarded as the empirical evidence that allows one to claim the source of a natural product to be bacterial derived, as it has been well established that certain bacteria are able to epimerize L-amino acids to their D-form. 4 In the case of isoleucine, however, α-epimerization would only affect the amino center, leaving the β-methyl center unchanged. Using this reasoning, L-isoleucine (4) can only be converted to its diastereomer, D-allo-isoleucine (5), and not its enantiomer, D-isoleucine (6). This is further supported by the fact that D-allo-isoleucine has been found previ...

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The taumycin A macrocycle: Asymmetric total synthesis and revision of relative stereochemistry

Maio

2015

Planta Med

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“…The cyclic octapeptides 2-6 were initially isolated and identified to be cathepsin B inhibitors. Subsequently, 1 was identified as a new linear decapeptide 1) from the same Streptomyces strain, 2,3) although its biological activity has not been evaluated yet. The draft genome sequence encodes four successive genes surA, surB, surC and surD, which are clustered and annotated as nonribosomal peptide synthetases (NRPSs) with 18 A domains in total.…”

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Diastereoselective Total Synthesis and Structural Confirmation of Surugamide F

Kuranaga

Fukuba

Ninomiya

et al. 2018

CHEMICAL & PHARMACEUTICAL BULLETIN

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Surugamide F is a linear decapeptide (1) isolated along with the cyclic octapeptides surugamides A-E (2-6), from a marine-derived Streptomyces species. The linear peptide 1 is produced by two nonribosomal peptide synthetases (NRPSs) encoded in adjacent open reading frames, which are further flanked by an additional pair of NRPS genes responsible for the biosyntheses of the cyclic peptides 2-6. While the cyclic peptides 2-6 were identified to be cathepsin B inhibitors, the biological activity of the new metabolite 1 still remained unclear. In order to elucidate its unique biosynthetic pathway and biological activity in detail, we planned to develop an efficient synthetic route toward 1. Here we report the diastereoselective total synthesis of 1, utilizing 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis. During this study, we found that the structural correction of 1 was required, due to the mislabeling of the commercially obtained 3-amino-2-methylpropionic acid, and the true structure of 1 was corroborated by the chemical synthesis and chromatographic comparison.

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“…operating on a 4-15 mg scale acid hydrolysis) 223,225,227 and often relied on the total synthesis, and chromatographic and/or spectroscopic comparison to multiple putative hydrolysis products. 222 Significantly, none of these "partial hydrolysis"…”

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confidence: 99%

“…220 As evidence of the effort required to secure unambiguous assignments, the regiochemistry of L and D-Leu in the cyclohexapeptide desotamide A (7.08) relied on the total synthesis of multiple isomers, 221 while the regiochemistry of L and D-Ile in the cyclooctapeptide surugamides A-E (7.09-7.13) relied on partial hydrolysis to tri and dipeptide fragments, which were in turn identified by a combination of Marfey's analyses and HPLC comparison to six synthetic dipeptides. 222 The regiochemistry of L and D-N-Me-Ala in companeramide B (7.14) was determined by a combination of partial acid hydrolysis, followed by HPLC isolation of a diagnostic tetrapeptide fragment, and an Advanced Marfey's analysis. 223 This regiochemical challenge is also well exemplified by kahalalide F (7.15), first isolated in 1993 as an exceptionally potent cytotoxic cyclic peptide from the sarcoglossan mollusc (Elysia rufescens) and its dietary green alga (Bryopsis sp.…”

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confidence: 99%

Marine biodiversity: exploring bioactive chemical space

Prasad¹

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This thesis is focused on exploration of Australian and Antarctica marine plants and invertebrates for the discovery of new and unusual natural products. A marine extract library (Capon) of over 2500 Australian and Antarctica marine plants and invertebrates was the platform for this research.High-throughput chemical profiling was executed by UHPLC-DAD to rapidly de-replicate, prioritise and fast track the chemical analysis of 2626 marine extracts. The acquired data was compiled as a chromatography-based library, establishing one central platform equipped with chromatography knowledge of the entire marine collection. Concurrently, assessing the biological potentials of the extract library was carried out in order to rapidly prioritise extracts. Employed biological assays included Bacillus Calmette-Guerin (BCG) screening and α 5 β 3 γ 2 -GABA A modulatory screening. Bioassay-guided fractionation was employed to guide the discovery of bioactive natural products. The prioritised hits were subjected to extraction, isolation and purification employing various techniques such as trituration, solvent-solvent partitioning, SPE fractionation, size exclusion chromatography, and analytical/semi-preparative and preparative HPLCs. Spectroscopic methods (UV-Vis, [α]

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Surugamides A–E, Cyclic Octapeptides with Four d-Amino Acid Residues, from a Marine Streptomyces sp.: LC–MS-Aided Inspection of Partial Hydrolysates for the Distinction of d- and l-Amino Acid Residues in the Sequence

Cited by 76 publications

References 22 publications

The taumycin A macrocycle: Asymmetric total synthesis and revision of relative stereochemistry

The taumycin A macrocycle: Asymmetric total synthesis and revision of relative stereochemistry

Diastereoselective Total Synthesis and Structural Confirmation of Surugamide F

Marine biodiversity: exploring bioactive chemical space

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