Cyclocinamide A. An Unusual Cytotoxic Halogenated Hexapeptide from the Marine Sponge <i>Psammocinia</i>

Clark, W. Dennis; Corbett, Thomas H.; Valeriote, Fred; Crews, Phillip

doi:10.1021/ja971638m

Cited by 59 publications

(63 citation statements)

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“…This was identical to that observed by Ireland14 using similar HPLC analysis conditions. Finally, the optical properties of the new sample of 2a ([α] 27 D = +32, in MeOH) matches that of our original compound ([α] 27 D = +29, in MeOH)3 in which l -BrTrp was established. Retention times for standard amino acid-FDAA derivatives: l -Asp 17.3 min, d -Asp, 20.0 min, d - i Ser 30.6 min, l - i Ser 31.3 min, l -DAP 49.1 min, l -5-BrTrp 49.8 min, d -DAP 50.1 min, d -5-BrTrp 53.2 min.…”

Section: Methodssupporting

confidence: 62%

“…The new sample of (+)-psymberin ( 1a ) was obtained from the XFD and XFM fractions, while (+)- cyclocinamide A ( 2a ) came from the XFM fraction. The identity of both compounds were confirmed from 1 H and 13 C NMR data and included in the case of 2a the additional diagnostic ESI-TOF-MS BrCl pseudomolecular ion cluster at [M+Na] + m/z 772 3. In the original structure elucidation of 2a , the i Ser OH 1 H NMR shift was reported at δ H 3.27 from water suppression data, but further inspection of the published 1 H NMR spectra of 2a reveals that in either DMSO- d 6 or DMSO- d 6 /benzene- d 6 , there are exchangeable proton signals at δ H 6.05 and δ H 6.15, respectively; however, these are not detected under CD 3 OD conditions.…”

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confidence: 97%

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Revisiting the Sponge Sources, Stereostructure, and Biological Activity of Cyclocinamide A

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The dramatic biogeographical variations in the secondary metabolites from Psammocinia aff. bulbosa have complicated our efforts to re-isolate the two most cytotoxic of its metabolites, (+)-psymberin and (+)-cyclocinamide A. Reported now are the results of a new study that demonstrates our ability to repeatedly isolate these two compounds through targeted collection efforts. Additional study of the new sample of (+)-cyclocinamide A has enabled finalizing its biological activity and absolute stereochemistry as 4S, 7S, 11S, 14S.In the early 1990s we began a campaign to survey the chemical ecology of Psammocinia aff. bulbosa communities from Papua New Guinea. It is now clear that a side-by-side chemical and taxonomic examination is obligatory to differentiate among populations of Psammocinia (Dictyoceratida, Irciniidae), Cacospongia (Dictyoceratida, Thorectidae), or Ircinia (Dictyoceratida, Irciniidae) 1 having very similar morphologies. Recognizing this critical step made it possible to engage in a meaningful synopsis of the chemical variations observed for a small library of P. aff. bulbosa specimens. Reported now are the final results of a project whose goals were to: (a) obtain fresh sponge specimens containing both psymberin and cyclocinamide A in order to facilitate on-going molecular genetics studies on their biosynthetic pathways, 2 (b) complete the full absolute chirality assignment for cyclocinamide A, 3,4 and (c) accumulate additional biological activity data for cyclocinamide A. 3 Outlined in Table 1 are an astonishing variety of biosynthetic products that we have observed to date from six distinct collections whose voucher material has each been identified as Psammocinia aff. bulbosa. The major constituents of specimens I -V range from sesterterpenes (variabilin 5 ), polyketides (preswinholide A 6 and swinholide A 6,7 ), a cyano-sponge cyclic hexapeptide (psymbamide A 7 ), a halogenated hexapeptide (cyclocinamide A 3 ), to a NRPS-PKS mixed biogenetic derived compound (psymberin 8 ). By contrast, meroterpenes (cacospongin B 9 and chromarol D 9 ) usually observed from sponges of Cacospongia-genus were isolated from sample VI. Though samples V and VI were obtained from adjacent sites, the chemical profiles of their major constituents clearly showed the biosynthetic machinery of these two sponge collections was distinct. These plus the other dramatic biogeographical *To whom correspondence should be addressed. phil@chemistry.ucsc.edu, Tel: (831) 459-2603. Fax: (831) Table 1 complicated our efforts to re-isolate the two most structurally unique of these metabolites, psymberin and cyclocinamide A.Before proceeding, it is important to briefly review the historical record highlighted in Figure 1 pertaining to absolute stereochemical assignments for psymberin and cyclocinamide A. The 5S, 8S, 9S, 11R, 13R, 15S, 16R, 17R structure we originally proposed for (+)-psymberin 8 (1a) was reaffirmed from two independent total syntheses of 1c. 10,11 The synthetic products also provided the basis for the 4S ...

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Section: Methodssupporting

confidence: 62%

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Revisiting the Sponge Sources, Stereostructure, and Biological Activity of Cyclocinamide A

et al. 2008

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“…There is only one published report of a plant-produced NRP in which the structure was confirmed by modem analytical method s. Jenett-Siems et al (1994) isolated ergobalansine, an ergopeptin e similar to ergotamine (Figure 7.lD) but having t-Ala in place of L-Pro, from a South American morning glory, Ipomoea piurensis. NRPs have been isolated from marine sponges, but the possibility that the compounds came from associated fungi or bacteria could not be excluded (Clark et al, 1997;Clark et al, 1998). There are no report s of molecular or biochemical characterization of NRP synthetases from any plant or animal.…”

Section: Introductionmentioning

confidence: 99%

Peptide Synthesis without Ribosomes

Walton

Panaccione

Hallen

2004

Advances in Fungal Biotechnology for Industry, Agriculture, and Medicine

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“…25 Otherwise, brominated and chlorinated derivatives are also frequently found in marine natural products showing high levels of biological activity. 26 However, the introduction of halogen atoms or even an epoxide ring do not add any increase of the phytotoxicity (compounds 5, 7,8,14,15,18,19), except for the isomeric epoxides cis,cis-germacranolide 18 and 19 which show an important increment of the phytotoxic activity, specially on lettuce germination. The different activity shown among epoxides at the C1-C10 in melampolides (7) and cis,cisgermacranolides (18 and 19) could relay on the different spatial disposition of the backbones, allowing an easier access in the last ones to the oxirane ring.…”

Section: Functional Group Influencementioning

confidence: 99%

Synthesis of melampolides and cis,cis-germacranolides as natural herbicide models

Macías¹,

Velasco²,

Álvarez³

et al. 2004

Tetrahedron

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Cyclocinamide A. An Unusual Cytotoxic Halogenated Hexapeptide from the Marine Sponge Psammocinia

Cited by 59 publications

References 10 publications

Revisiting the Sponge Sources, Stereostructure, and Biological Activity of Cyclocinamide A

Revisiting the Sponge Sources, Stereostructure, and Biological Activity of Cyclocinamide A

Peptide Synthesis without Ribosomes

Synthesis of melampolides and cis,cis-germacranolides as natural herbicide models

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