Oceanalin A, a Hybrid α,ω-Bifunctionalized Sphingoid Tetrahydroisoquinoline β-Glycoside from the Marine Sponge <i>Oceanapia</i> sp.

Makarieva, Tatyana N.; Денисенко, В. А.; Dmitrenok, Pavel S.; Guzii, Alla G.; Santalova, Elena A.; Stonik, Valentin A.; MacMillan, John B.; Molinski, Tadeusz F.

doi:10.1021/ol050796c

Cited by 32 publications

(47 citation statements)

References 23 publications

(21 reference statements)

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“…Oceanalin A (compound 79 in Fig. 7) is an α,ω-bifunctionalized sphingoid base-tetrahydroisoquinoline from the sponge Oceanapia species that in its glycoside form (R = galactose) has in vitro antifungal activity against C. glabrata and has been suggested to block sphingolipid biosynthesis by inhibiting ceramide synthase (189). …”

Section: αω-Sphingoids: “Two-headed” Sphingoid Base-like Compoundsmentioning

confidence: 99%

Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols

Pruett

Bushnev

Hagedorn

et al. 2008

Journal of Lipid Research

397

341

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“Sphingosin” was first described by J. L. W. Thudichum in 1884 and structurally characterized as 2S,3R,4E-2-aminooctadec-4-ene-1,3-diol in 1947 by Herb Carter, who also proposed the designation of “lipides derived from sphingosine as sphingolipides.” This category of amino alcohols is now known to encompass hundreds of compounds that are referred to as sphingoid bases and sphingoid base-like compounds, which vary in chain length, number, position, and stereochemistry of double bonds, hydroxyl groups, and other functionalities. Some have especially intriguing features, such as the tail-to-tail combination of two sphingoid bases in the α,ω-sphingoids produced by sponges. Most of these compounds participate in cell structure and regulation, and some (such as the fumonisins) disrupt normal sphingolipid metabolism and cause plant and animal disease. Many of the naturally occurring and synthetic sphingoid bases are cytotoxic for cancer cells and pathogenic microorganisms or have other potentially useful bioactivities; hence, they offer promise as pharmaceutical leads. This thematic review gives an overview of the biodiversity of the backbones of sphingolipids and the broader field of naturally occurring and synthetic sphingoid base-like compounds.

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Section: αω-Sphingoids: “Two-headed” Sphingoid Base-like Compoundsmentioning

confidence: 99%

Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols

Pruett

Bushnev

Hagedorn

et al. 2008

Journal of Lipid Research

397

341

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“…Two-headed β-glycoside oceanalin A ( 164 ), a unique natural compound of hybrid alkaloidal sphingolipid, was also isolated from the marine sponge Oceanapia sp. [90]. The remarkable finding associated to oceanalin A structure was the discovery of unprecedented confluence of sphingolipid and isoquinoline pathways in marine natural product biosyntheses.…”

Section: Glycosides Of Non-isoprenoid Aglyconesmentioning

confidence: 99%

“…As result of the studies on biological properties of these bipolar glycosides, antibacterial activity against Staphylococcus aureus , cytotoxic activity against mouse Ehrlich carcinoma cells [81], antifungal activity against the pathogenic fluconazole-resistant yeast Candida glabrata [87,90], selective DNA-damaging action [89], anticarcinogenic [91], and proapoptotic properties [91,92,93] at their micromolar concentration were indicated.…”

Section: Glycosides Of Non-isoprenoid Aglyconesmentioning

confidence: 99%

Glycosides from Marine Sponges (Porifera, Demospongiae): Structures, Taxonomical Distribution, Biological Activities and Biological Roles

et al. 2012

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“…In fact, the activity of (+)- 1 is quite singular; it not mimicked by simple synthetic stereoisomers or analogs. Antifungal activity in simple vicinal aminoalkanols has been observed for other natural products, such as oceanapiside,20 oceanalin,21 even sphingosine and its synthetic short-chain analogs (C 6 ), irrespective of the relative configurations 22. Consequently, the stringent stereochemical requirements observed for antifungal activity properties in 1 were unexpected and surprising.…”

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confidence: 99%

Zwittermicin A: Synthesis of analogs and structure–activity studies

Rogers

Dalisay

Molinski

2010

Bioorganic & Medicinal Chemistry Letters

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Analogs and diastereomers of the natural product zwittermicin A were prepared. SAR studies of these compounds reveal the antifungal activity to be dependent singularly upon the natural constitution and configuration. Keywordsantifungal; amino alcohol; synthesis (+)-Zwittermicin A (1) (ZwA) is a highly polar aminopolyol antibiotic isolated from the soilborne bacterium Bacillus cereus. 1 Compound 1 was first reported in 1994 and shows significant activity against human pathogenic yeast and phytopathogenic fungi. 1,2 More importantly 1 has been shown to work synergistically with endo-toxin produced by Bacillus thuringensis for control of gypsy moth. 3 Research has shown strains of B. cereus producing 1 to be ubiquitous in the soil 1c and may be more benign to the environment than some synthetic pesticides. 4 Biosynthesis of 1 arises from a non-ribosomal peptide synthetase/polyketide synthase pathway (NRPS/PKS) involving two new type 1 PKS extender units: hydroxymalonyl-acyl carrier protein (ACP) and aminomalonyl-ACP. 5 Preliminary studies show that 1 appears to exhibit a unique mechanism of action. 6 Investigations of ZwA-resistant mutants found that the resistance mapped to rpoB and rpoC, 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. genes that encode subunits of RNA polymerase. 6 However, 1 showed no effect on total RNA or DNA synthesis implying a mechanism of action that differs from that of other antibiotics that target RNA polymerase. 6 Previously, we synthesized (−)-1, the enantiomer of ZwA, its diastereomer 2, and analogs 5 through 10 (Figure 1). 7 This report describes the synthesis of the additional diastereomers 3 and 4 as well as analogs ent-6, 11 and 12 together with a comprehensive SAR study of all compounds. NIH Public AccessAuthor Manuscript Bioorg Med Chem Lett. Author manuscript; available in PMC 2011 April 1.During the course of our synthesis of (−)-1 a number of models were made to evaluate synthetic strategies and some of these were later used to make analogs 11 and 12 as shown in Scheme 1. Analog ent-6 was synthesized by reduction of diazide 13 (Scheme 1). 8 The known alcohol 14 9 was converted to aldehyde 15 in three high-yielding steps; MOM protection of the primary OH group, 10 desilylation of the primary OTBS group, 11 followed by Swern 12 oxidation. Evan's aldol addition of the boron enolate of chiral glycolate equivalent 16 13 to 15 (dr 47:1) followed by separation and removal of the chiral auxiliary under standard conditions afforded carboxylic acid 17 (57% over two steps). 14 Coupling of 17 to known N-ureido-L-1,3-diaminopropion...

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Oceanalin A, a Hybrid α,ω-Bifunctionalized Sphingoid Tetrahydroisoquinoline β-Glycoside from the Marine Sponge Oceanapia sp.

Cited by 32 publications

References 23 publications

Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols

Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols

Glycosides from Marine Sponges (Porifera, Demospongiae): Structures, Taxonomical Distribution, Biological Activities and Biological Roles

Zwittermicin A: Synthesis of analogs and structure–activity studies

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