Isolation of Calyculins, Calyculinamides, and Swinholide H from the New Zealand Deep-Water Marine Sponge <i>Lamellomorpha</i> <i>strongylata</i>

Dumdei, Eric J.; Blunt, John W.; Munro, Murray H. G.; Pannell, Lewis K.

doi:10.1021/jo961745j

“…29 Lactone 14a was reduced in the presence of an excess of LiAlH 4 . Surprisingly, the TBS group was cleaved during the course of the reaction and triol 15 was obtained (Scheme 4).…”

Section: Conversion To the Alkynementioning

confidence: 99%

Towards the total synthesis of calyculin C: preparation of the C9–C25 spiroketal-dipropionate unit

Habrant

¹

,

Koskinen

²

2010

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An asymmetric synthesis of the C 9 -C 25 spiroketal fragment of calyculin C is described. Key steps include two crotylation reactions using successively Brown's reagent and (Z)-crotyltrifluorosilane for the formation of the anti, anti, anti stereotetrad, ynone formation by a Pd-catalyzed coupling of a thiol ester with a terminal alkyne and a double intramolecular hetero-Michael addition for the stereoselective construction of the spiroketal framework.

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“…1) have many structural features in common with the calyculins but differ markedly from them in having a methyl group at C-32 and an unusual trimethoxy rhamnose group at position C-21. Like the calyculinamides, and unlike calyculin A, the clavosines possess an amide at the end of their tetraene tail, as found in the calyculinamides (14). Clavosine A differs from clavosine B in having Z (cis) rather than E (trans) geometry at the C-2ϭC-3 double bond.…”

mentioning

confidence: 99%

“…Calyculin A was also shown to have tumor-promoting activity as potent as that of okadaic acid (7). Many additional calyculins (8 -13), and the structurally related calyculinamides (11,14), have since been identified.Recently we reported the isolation of two novel glycosylated members of the calyculin family, clavosines A and B from the marine sponge Myriastra clavosa (15). Clavosines A and B are potent inhibitors of mammalian PP-1c and PP-2Ac and were found to be more cytotoxic overall than the calyculins and the calyculinamides (14, 15) in the National Cancer Institute (NCI) screening panel of tumor cell lines (16).…”

mentioning

confidence: 99%

“…Calyculin A was also shown to have tumor-promoting activity as potent as that of okadaic acid (7). Many additional calyculins (8 -13), and the structurally related calyculinamides (11,14), have since been identified.…”

mentioning

confidence: 99%

“…Clavosines A and B are potent inhibitors of mammalian PP-1c and PP-2Ac and were found to be more cytotoxic overall than the calyculins and the calyculinamides (14,15) in the National Cancer Institute (NCI) screening panel of tumor cell lines (16). The polyfunctional structure of clavosines A and B and calyculin A is depicted in linear diagrams (Fig.…”

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confidence: 99%

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Inhibition of Protein Phosphatase-1 by Clavosines A and B

McCready¹,

Islam²,

Schmitz³

et al. 2000

Journal of Biological Chemistry

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Site-directed mutagenesis was used to investigate the mechanism of interaction between the catalytic subunit of human protein phosphatase-1 (PP-1c␥) and members of the calyculin family of toxins. Clavosines A and B are related to calyculins but are glycosylated with a trimethoxy rhamnose group. We provide experimental evidence implicating Tyr-134 as an important residue in PP-1c␥ that mediates interactions with the calyculins. Mutation of Tyr-134 to Phe, to prevent hydrogen bond formation, resulted in a slight increase in sensitivity of PP-1c␥ to clavosines A and B and calyculin A. In contrast, a Y134A mutant was 10-fold less sensitive to inhibition by all three inhibitors. The greatest effect on inhibition was found by substituting an Asp for Tyr-134 in the phosphatase. Clavosine B inhibited PP-1c␥ Y134D with a 310-fold decrease in potency. Clavosine A and calyculin A were also markedly poorer inhibitors of this mutant. These results suggest that a hydrogen bond between Tyr-134 and the calyculins is unlikely to be essential for inhibitor binding to the phosphatase. Serine/threonine protein phosphatases are highly conserved enzymes, which have been isolated from numerous eukaryotic and prokaryotic organisms (1, 2). Eukaryotic protein phosphatases are inhibited by a structurally diverse array of natural product toxins. These include the polyether okadaic acid from marine dinoflagellates, cyclic peptide microcystins and nodularins from cyanobacteria, and the spiroketal calyculins isolated from marine sponges (3).The first member of the calyculin family of phosphatase inhibitors was identified in 1986 (4). Calyculin A was originally purified from a hydrophobic extract of the marine sponge Discodermia calyx. It was found to be cytotoxic toward P388 and L1210 leukemia cells and to be a strong inhibitor of starfish egg development (4, 5). It was subsequently characterized as a powerful inhibitor of the catalytic subunits of type 1 and 2A protein phosphatases, PP-1c 1 and PP-2Ac, two of the four major eukaryotic serine/threonine protein phosphatases (6). Calyculin A was also shown to have tumor-promoting activity as potent as that of okadaic acid (7). Many additional calyculins (8 -13), and the structurally related calyculinamides (11,14), have since been identified.Recently we reported the isolation of two novel glycosylated members of the calyculin family, clavosines A and B from the marine sponge Myriastra clavosa (15). Clavosines A and B are potent inhibitors of mammalian PP-1c and PP-2Ac and were found to be more cytotoxic overall than the calyculins and the calyculinamides (14, 15) in the National Cancer Institute (NCI) screening panel of tumor cell lines (16). The polyfunctional structure of clavosines A and B and calyculin A is depicted in linear diagrams (Fig. 1a) and space filling models (Fig. 1b). The clavosines (Fig. 1) have many structural features in common with the calyculins but differ markedly from them in having a methyl group at C-32 and an unusual trimethoxy rhamnose group at position C-21. Like the...

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Porifera (Sponges)–1

Kornprobst

¹

2014

Encyclopedia of Marine Natural Products

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The article contains sections titled: Overview of the Universe of Sponges Metabolites of Calcarea (Calcareous Sponges) General Characteristics of Calcarea Fatty Acids Sterols Non‐Nitrogenous Derivatives of Species of the Genus Leucetta Imidazole Alkaloids and Zinc Complexes Isolated from the Genera Leucetta , Leucosolenia , and Clathrina αω‐ Bis Long‐Chain Aminoalcohols Nitrogen‐Containing Macrolides and Cyclic Peptides Other Nitrogen‐Containing Compounds of Calcarea Metabolites of Hexactinellida Classification and Membrane Constituents of Demospongiae Classification Some Physical Observations on Demosponges Shape and Size Consistency Color and Odor Diversity of Membrane Constituents: Some Examples Phospholipids and “Demospongic Acids” Fatty Acids with 5,9 Dienic Structure Other Mono‐ and Polyunsaturated Fatty Acids Branched Fatty Acids Isoprenic Acids Cyclopropanic Acids Brominated Acids 2‐ O Substituted Acids Sulfur Derivatives of Demospongic Acids Intracellular Localization and Biological Activity of Demospongic Acids Brief Reminder About Conventional Sterols Unconventional Sterols Produced by Changes in the Tetracyclic System Unconventional Sterols Produced by Polymethylation of the Side Chain Sterols with Degraded Side Chains Sterols and Stanols with Cyclopropanic and Cyclopropenic Side Chains Secosterols Polyhydroxylated Steroids and Derivatives, Peroxysterols Sulfated Sterols Chlorinated Sterols and Sterones Nitrogen‐Containing Sterols Glycolipids Secondary Metabolites of Homoscleromorpha Fatty Acids, Polyketides and Oxylipins of Plakinastrella and Plakortis Cyclic Peroxides and Peroxylactones from Plakinastrella and Plakortis Glycosides Polyhydroxylated Sterols of Oscarella lobularis Alkaloids and Other Original Nitrogen Derivatives of Plakortis and Corticium Secondary Metabolites of Astrophorida Acetylenic Fatty Acids of Stelletta Cyclitol Derivatives Glycolipids: Caminosides and Pachymosides Triterpenes of Malabaricane and Isomalabaricane: Sesterterpenes Triterpenic Glycosides and Steroidal Glycosides Substituted Tetramic Acids and Derived Glycosides Erylusamines, Erylusine, and Erylusidine Cyclic Depsipeptides, Peptolides, and Macrolactones Nitrogen‐Containing Terpenes Bengazoles and Bengamides Atypical Nitrogenous Derivatives Phosphorus‐Containing Derivatives Aromatic and Heteroaromatic Sulfated Derivatives Isotactic Polymethoxydienes of Myriastra clavosa

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Isolation of Calyculins, Calyculinamides, and Swinholide H from the New Zealand Deep-Water Marine Sponge Lamellomorpha strongylata

Cited by 67 publications

References 14 publications

Towards the total synthesis of calyculin C: preparation of the C9–C25 spiroketal-dipropionate unit

Towards the total synthesis of calyculin C: preparation of the C9–C25 spiroketal-dipropionate unit

Inhibition of Protein Phosphatase-1 by Clavosines A and B

Porifera (Sponges)–1

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