Papuamides A−D, HIV-Inhibitory and Cytotoxic Depsipeptides from the Sponges Theonella mirabilis and Theonella swinhoei Collected in Papua New Guinea

Ford, Paul W.; Gustafson, Kirk R.; McKee, Tawnya C.; Shigematsu, Nobuharu; Maurizi, Laura K.; Pannell, Lewis K.; Williams, David E.; Silva, E. Dilip de; Lassota, Peter; Allen, Theresa M.; Soest, R.W.M. van; Andersen, Raymond J.; Boyd, Michael R.

doi:10.1021/ja990582o

Cited by 214 publications

(155 citation statements)

References 25 publications

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“…On the basis of these encouraging results, other Lewis acidic metal triflates -Sc(OTf) 3 , Er(OTf) 3 , Eu (OTf) 3 , Sm(OTf) 3 Ce(OTf) 3 , Ag(OTf), Cu(OTf) 2 , and Zn(OTf) 2 -were also screened as potential catalysts of ammonolysis ( Table 1). As expected, Sc(OTf) 3 was as reactive as Yb (OTf) 3 and both proved to be the most active Lewis acid catalysts tested.…”

Section: Resultsmentioning

confidence: 99%

“…Although Er (OTf) 3 , Eu(OTf) 3 and Sm(OTf) 3 gave slower reactions that went to completion in 5 minutes, reaction with Eu(OTf) 3 and Sm(OTf) 3 resulted in the production of fewer side products. The use of Ce(OTf) 3 , Ag(OTf), Cu(OTf) 2 and Zn(OTf) 2 as catalysts resulted in slower reactions that were complete in 20-30 minutes with moderate yields (Table 1). In the best cases, the yield of ammonolysis product was improved and the time of reaction drastically reduced.…”

Section: Resultsmentioning

confidence: 99%

“…1 Likewise, the papuamides were isolated from the sponges Theonella mirabilis and Theonella swinhoe by Boyd and coworkers and shown to also possess both antitumor and anti-HIV activities. 2 To date, syntheses of DiMeGln have been reported by Joullié, 3 Hamada, 4 , and ourselves. 5 In all three cases, however DiMeGln was synthesized with acid-labile protecting groups on N α .…”

Section: Introductionmentioning

confidence: 96%

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Synthesis of N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine: An Application of Lanthanide-Catalyzed Transamidation

Çalimsiz

Lipton

2005

J. Org. Chem.

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3S, was synthesized from t-butyl 3S,. This synthesis involved selective deprotection of a Boc group from a lactam nitrogen in the presence of a t-butyl ester, Fmoc protection of the lactam, and a lanthanidecatalyzed transamidation reaction of the Fmoc-protected lactam using ammonia and dimethylaluminum chloride. The scope of Lewis acid-catalyzed transamidation of acylated lactams was explored through the variation of lanthanide, lactam, acyl group, amine and aluminum reagent. The reactivity of various metal triflates was found to vary in the qualitative order: Yb∼Sc>Er∼Eu∼Sm>Ce∼Ag I >Cu II ∼Zn. Intriguingly, catalysis was only observed when ammonia was the nitrogen nucleophile; addition of other amidoaluminum complexes to acyl lactams was found to be insensitive to the addition of lanthanides.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Synthesis of N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine: An Application of Lanthanide-Catalyzed Transamidation

Çalimsiz

Lipton

2005

J. Org. Chem.

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“…In this report as part of an investigation of active sponge extracts against infectious diseases two new cyclic heptapeptides, stylisin 1 (1) and stylisin 2 (2), and the known peptide phakellistatin 13 (3) were isolated as well as the known alkaloids sceptrin (4), stevensine (5), and oroidin (6). Here we describe the isolation and structure elucidation of the two new cyclic peptides.…”

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confidence: 91%

Cyclic Heptapeptides from the Jamaican Sponge Stylissa caribica

et al. 2006

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Two new cyclic heptapeptides, stylisin 1(1) and stylisin 2 (2), were isolated and characterized from the Jamaican sponge Stylissa caribica, in addition to the cyclic heptapeptide phakellistatin 13 (3) and the known bromopyrrole alkaloids sceptrin (4), stevensine (5), and oroidin (6). The new structures were assigned on the basis of 1D and 2D NMR spectroscopic data, as well as chemical methods for the elucidation of the absolute configuration of amino acids. The peptides and alkaloids have been evaluated for their antimicrobial, antimalarial, anticancer, anti-HIV-1, antiMtb, and antiinflammatory activities.Peptides are well-established bioactive metabolites from marine invertebrates , and include linear peptides, , depsipeptides, , and cyclic -and bicyclic peptides. , Species of the sponge genera Phakellia and Axinella have yielded several bioactive cyclic peptides -reported to have cytotoxic activity against a number of cancer cell lines. It has been noted that most of these cyclic peptides are rich in proline amino acid moieties, which may be in either cis or trans conformation. There is evidence that some of the sponge cyclic peptides are able to bind undetectable quantities of a very potent antineoplastic substance that can only be revealed through biological assays.In this report as part of an investigation of active sponge extracts against infectious diseases two new cyclic heptapeptides, stylisin 1 (1) and stylisin 2 (2), and the known peptide phakellistatin 13 (3) were isolated as well as the known alkaloids sceptrin (4), stevensine (5), and oroidin (6). Here we describe the isolation and structure elucidation of the two new cyclic peptides. Several reports describing the chemistry of different marine sponges belonging to Stylissa spp. have been published including aldisines from Stylissa massa, latonduines from Stylissa carteri, and massadine from Stylissa aff. massa. In a study regarding the chemistry of Stylissa caribica Lehnert & van Soest, 1998 (Halichondrida: Dictyonellidae), a series of bromopyrrole alkaloids have been identified. No cyclic peptides have been previously reported from Stylissa species, and these results have suggested a possible microbial or symbiotic origin for these metabolites. HHS Public Access Results and DiscussionThe sponge extract was dissolved in ethanol and subjected to silica gel vacuum-liquid chromatography followed by column chromatography, Sephadex LH-20, RP HPLC, and PTLC chromatography to yield two new cyclic heptapeptides, stylisin 1 (1) and stylisin 2 (2), the known cyclic peptide phakellistatin 13 (3), and the known alkaloids sceptrin, stevensine, and oroidin (4-6).Stylisin 1 (1) ( (Figures 2 and 3). Each amino acid was connected to the adjacent amino acid in a cyclic form based on the HMBC correlations between the αH and NH with the adjacent CO. An HMBC correlation was assigned between the isoleucine NH and CO of Pro1 at δ 171.48 and generated a partial structure for a Pro1-Ile. The amide proton at δ 7.44 of Phe gave an HMBC correlation to CO of ...

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“…Subsequent examination of 1D-spectra of 1 reflected characteristic features of a peptide, such as an abundance of exchangeable N-H protons (δ H 6.55-9.05) and carbonyl signals (δ C 169.9-179.6) in the 1 H and 13 C NMR spectra, respectively. However, the interpretation of NMR spectra of 1 was hampered by the existence of multiple conformations in several of the common NMR solvents (MeOH-d 4 , CD 3 CN:DMSO-d 6 and DMSO-d 6 ). Attempts to improve resolution by employing acetoned 6 and DMF-d 7 as solvents failed due to poor solubility of 1.…”

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confidence: 99%

Theopapuamide, a Cyclic Depsipeptide from a Papua New Guinea Lithistid Sponge Theonella swinhoei

et al. 2006

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Theopapuamide (1), a new cytotoxic peptide has been isolated from the lithistid sponge Theonella swinhoei from Papua New Guinea. The structure was established by analysis of NMR, mass spectrometry and chemical methods. The undecapeptide (1) contains several unusual amino acid residues, of which the occurrence of β-methoxyasparagine and 4-amino-5-methyl-2,3,5-trihydroxyhexanoic acid (Amtha) is unprecedented in natural peptides. Compound 1 also contains a amide linked fatty acid moiety, 3-hydroxy-2,4,6-trimethyl-octanoic acid (Htoa). Theopapuamide (1) was cytotoxic against CEM-TART and HCT-116 cell lines with EC 50 values of 0.5 μM and 0.9 μM respectively.Marine sponges have proven to be a significant source of biologically active cyclic peptides and depsipeptides. 1 Among these sponge depsipeptides, callipeltin A (from New Caledonian sponge Callipelta sp.), 2 neamphamide A (from a Papua New Guinea sponge Neamphius huxleyi) 3 and Papuamides A-B (from Papua New Guinea sponges Theonella mirabilis and Theonella swinhoei) 4 are well known for their potent HIV-inhibitory activity and their structurally unique features incorporating several modified amino acid residues. For instance, the atypical amino acid residues 3,4-dimethyl-L-glutamine and β-methoxytyrosine are common to all of the above mentioned marine depsipeptides but to date have not been described elsewhere. The rarity of these atypical amino acid residues has inspired their chemical synthesis. 5 The structural diversity found among lithistid sponge metabolites (genus Theonella and Callipelta) has been attributed to symbiotic microorganisms. 1 As part of our continuing studies on Theonella swinhoei from Papua New Guinea, 6 the aqueous CH 3 CN extract of the sponge was analyzed and proved active in an in vitro anti-HIV assay. Fractionation of the active extract resulted in the isolation of a new cyclic depsipeptide, theopapuamide (1). This paper describes the isolation, structure elucidation, and stereochemical analysis of theopapuamide (1).The crude aqueous CH 3 CN extract of T. swinhoei (family Theonellidae) was concentrated under vacuum and fractionated by C18 flash column chromatography. Further purification on Diaion HP-20 resin followed by CN-HPLC afforded the new cyclic undecapeptide, *To whom correspondence should be addressed. Tel: (801) In conjunction with NMR analysis, the gross structure elucidation of 1 was guided by standard amino acid analysis, 9 which revealed molar concentrations of ~1:2:1 for Asx, Thr and Leu respectively. The presence of two N-methylated amino acid residues were suggested based on the characteristic 1 H and 13 C chemical shifts of the N-methyl groups at δ H 2.81 (δ C 30.8) and δ H 2.88 (δ C 31.8). HMBC correlations were used to identify these N-methylated amino acids as NMeLeu and NMeGln, respectively. Additionally, the presence of a methoxy-bearing amino acid residue was suggested by the characteristic 1 H and 13 C chemical shifts of the O-methyl group at δ H 3.34 (δ C 60.3). Based on HMBC correlations, the methoxy...

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Papuamides A−D, HIV-Inhibitory and Cytotoxic Depsipeptides from the Sponges Theonella mirabilis and Theonella swinhoei Collected in Papua New Guinea

Cited by 214 publications

References 25 publications

Synthesis of N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine: An Application of Lanthanide-Catalyzed Transamidation

Synthesis of N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine: An Application of Lanthanide-Catalyzed Transamidation

Cyclic Heptapeptides from the Jamaican Sponge Stylissa caribica

Theopapuamide, a Cyclic Depsipeptide from a Papua New Guinea Lithistid Sponge Theonella swinhoei

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