Marine Alkaloids. 19. Three New Alkaloids, Securamines E−G, from the Marine Bryozoan <i>Securiflustra securifrons</i>

Rahbæk, Lisa; Christophersen, Carsten

doi:10.1021/np960602p

Cited by 51 publications

(42 citation statements)

References 3 publications

(7 reference statements)

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“…87 The final member of the Flustridae of note is Securiflustra securifrons, which produces securines A and B 95-96, 88 together with securamines A-G 97-103. 88,89 As with the isolated products of C. papyracea, all of the metabolites of S. securifrons are structurally similar.…”

Section: Suborder Malacostegamentioning

confidence: 94%

Bryozoan Metabolites: An Ecological Perspective

2007

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Section: Suborder Malacostegamentioning

confidence: 94%

Bryozoan Metabolites: An Ecological Perspective

2007

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“…[1][2][3] A related bryozoan Securiflustra securifrons also produces the securines and securamines, 4,5 and they are plausible biogenetic precursors to the chartellines. It was reported that solutions of securine B 1 in DMSO-d 6 converted into securamine B 2, presumably via 1a , Scheme 1.…”

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confidence: 99%

“…One could imagine that if this isomerization were carried out in the presence of an electropositive source of chlorine, 1 could be converted into chartelline C 3 through the intermediacy of 1b and 1c. The transformation of 1c into 3 can be written as a [1,5]-shift and is a key step in the recently reported biogenetically inspired strategy for the synthesis of 3 by Baran and Shenvi. 6,7 Several other groups have reported on synthetic approaches to chartelline C 6,[8][9][10][11] as well as related alkaloids.…”

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confidence: 99%

Studies towards the synthesis of the marine alkaloid chartelline C

Black

Hecker²,

Magnus³

2007

Tetrahedron Letters

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The 2,6-dibromoindole 5 underwent regioselective Sonogashira coupling at the 2 position with simple acetylenic partners. While, the imidazole-acetylene 16 failed to couple to 5, the cyclic carbonate 19 succeeded to give 20, which was further elaborated into the indole-imidazole 23. KeywordsChartelline C; securines; securamines; biogenetic; Sonogashira couplingThe chartelline marine alkaloids were isolated from the bryozoan Chartella papyracea and characterized in the 1980's. 1-3 A related bryozoan Securiflustra securifrons also produces the securines and securamines, 4,5 and they are plausible biogenetic precursors to the chartellines. It was reported that solutions of securine B 1 in DMSO-d 6 converted into securamine B 2, presumably via 1a , Scheme 1. 4 Redissolving 2 in CDCl 3 converted 2 back into 1. One could imagine that if this isomerization were carried out in the presence of an electropositive source of chlorine, 1 could be converted into chartelline C 3 through the intermediacy of 1b and 1c. The transformation of 1c into 3 can be written as a [1,5]-shift and is a key step in the recently reported biogenetically inspired strategy for the synthesis of 3 by Baran and Shenvi. 6,7 Several other groups have reported on synthetic approaches to chartelline C 6,8-11 as well as related alkaloids. 12,13 Our plan was also based on the supposition that the spiro-β-lactam in 3 could arise from a late stage oxidative cyclization of a suitable macrolactam. 14 The macrolactam precursor to 1c, namely 1, was envisioned as arising from macrolactamization, and to eventually achieve this a regioselective Sonogashira coupling at the 2-position of a 2-halo-6-bromoindole was required as a starting point. The only selective coupling of an acetylene at the 2-position of an indole that has a 6-bromo substituent was a 2-iodo-6-bromoindole, 7 and since this compound required a six step synthesis from 6-bromoindole, we were interested to see if a 2,6-dibromoindole exhibited any selectivity in a Sonogashira coupling reaction.Indole-3-acetonitrile 4 15,16 was regioselectively brominated using a known protocol 17 to give 5 (after t-butyl carbamate protection), Scheme 2. Exposure of 5 to standard Sonogashira © 2007 Elsevier Ltd. All rights reserved.Tel +1 512 471 3966: Fax +1 512 471 7839: p.magnus@mail.utexas.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. coupling reaction conditions proceeded with complete regioselectivity to give the 2-coupled indoles 6, 7 and 8 respectively. It was found that the choice of protecting group on the indole nitrogen atom was essential to achieving r...

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“…A series of investigations resulted in the isolation of a host of novel natural products, including the flustramines (1-3) , chartellines (4)(5)(6), and chartellamides (7). Additionally, two reports describe the securamines (8,9), which are characterized by a central tricyclic pyrroloindole core and a highly substituted imidazole ring linked via a modified isoprene subunit and a macrocyclic cis-enamide ( Fig. 1).…”

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confidence: 99%

“…1). Interestingly, pyrroloindole securamine A (1) exists in a synthetically exploitable solvent-dependent equilibrium with ring-opened isomer securine A (2) (8,9).…”

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confidence: 99%

Efficient construction of the securine A carbon skeleton

Korakas

Chaffee

Shotwell

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Securamine A is a structurally intriguing alkaloid possessing a pyrroloindole core joined via a modified isoprene subunit to a functionalized imidazole ring. Recent synthetic efforts in this laboratory have resulted in the efficient construction of key lactone 36, which undergoes tandem azide reduction͞ring expansion to macrolactam 37. Macrolactam 37 possesses the complete macrocyclic core of securamine A. T he bryozoans Flustra foliacea and Chartella papyracea have proven to be a rich source of structurally unprecedented halogenated indole-alkaloids. A series of investigations resulted in the isolation of a host of novel natural products, including the flustramines (1-3) , chartellines (4-6), and chartellamides (7). Additionally, two reports describe the securamines (8, 9), which are characterized by a central tricyclic pyrroloindole core and a highly substituted imidazole ring linked via a modified isoprene subunit and a macrocyclic cis-enamide (Fig. 1). Interestingly, pyrroloindole securamine A (1) exists in a synthetically exploitable solvent-dependent equilibrium with ring-opened isomer securine A (2) (8, 9).Despite synthetic work toward both the flustramines (10-12) and chartellines͞chartellamides (13,14), no efforts toward the construction of the securamine͞securine skeleton have yet been reported (15,16). Intrigued by the densely functionalized heterocycles characterizing the securamines, in addition to reports that securine A serves as a biogenic precursor for a variety of other natural products (8, 9), we have focused our efforts on the efficient construction of 1 and 2.Retrosynthetically, securine A was visualized as the union of two heterocyclic subunits (pyrroloindole and imidazole) joined into a macrocycle via two tethers (the isoprene and enamide) (Fig. 2). We envisioned that the elimination-prone C(10) neopentyl chloride moiety (13,14) could be installed at a late stage via direct chlorination of the corresponding alcohol, whereas the sensitive enamide-moiety could be generated from a C(2)-C(3) amido-alcohol (5). Orthogonal diol 5 would arise via macrocyclization of the corresponding amino alcohol, which could be accessed directly from a C(2)-C(3) olefin (17, 18). Key indole 6 could be accessed from internal alkyne 7, which would be generated from elaboration of 8. Imidazole 8 could be derived from the condensation of two equivalents of formamide with ␣-bromo ketone 9 (19). MethodsUnless otherwise stated, reactions were performed in flamedried glassware under a nitrogen atmosphere by using freshly distilled solvents. Experimental and spectral data pertaining to compounds 7, 11-15, 18-20, 22, and 25-40 can be found in Supporting Text, which is published as supporting information on the PNAS web site. ResultsExposure of 10 to bromine and acetic acid gave smooth conversion to the corresponding ␣-bromoketone. Subsequent dissolution in neat formamide and prolonged heating gave imidazole 8 in 80% overall yield after two recrystallizations (19). Benzylation at N(5) and bromination at C(4) proceeded in a...

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Marine Alkaloids. 19. Three New Alkaloids, Securamines E−G, from the Marine Bryozoan Securiflustra securifrons

Cited by 51 publications

References 3 publications

Bryozoan Metabolites: An Ecological Perspective

Bryozoan Metabolites: An Ecological Perspective

Studies towards the synthesis of the marine alkaloid chartelline C

Efficient construction of the securine A carbon skeleton

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