Spongistatins, Cynachyrolides, or Altohyrtins? Marine Macrolides in Cancer Therapy

Pietruszka, Jörg

doi:10.1002/(sici)1521-3773(19981016)37:19<2629::aid-anie2629>3.0.co;2-a

Cited by 62 publications

(4 citation statements)

References 4 publications

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“…In designing a small-molecule library with increased structural complexity accessible by a domain shuffling (DS) strategy, we were inspired by the numerous pyran-containing macrocycles found in nature, such as rapamycin (11), bryostatin (12), and spongistatin (13), among others (14-18), which contain a high ratio of sp 3 -hybridized atoms and stereogenic centers. In light of their unique structural features (19), macrocycles in general have been the focus of a number of library synthesis efforts (9,(20)(21)(22)(23)(24)(25)(26)(27), although only a few libraries centered on pyran-containing macrocycles (24)(25)(26).…”

supporting

confidence: 57%

Fragment-based domain shuffling approach for the synthesis of pyran-based macrocycles

Comer

Joliton

et al. 2011

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

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Complexity and the presence of stereogenic centers have been correlated with success as compounds transition from discovery through the clinic. Here we describe the synthesis of a library of pyran-containing macrocycles with a high degree of structural complexity and up to five stereogenic centers. A key feature of the design strategy was to use a modular synthetic route with three fragments that can be readily interchanged or "shuffled" to produce subtly different variants with distinct molecular shapes. A total of 352 macrocycles were synthesized ranging in size from 14-to 16-membered rings. In order to facilitate the generation of stereostructure-activity relationships, the complete matrix of stereoisomers was prepared for each macrocycle. Solid-phase assisted parallel solution-phase techniques were employed to allow for rapid analogue generation. An intramolecular nitrileactivated nucleophilic aromatic substitution reaction was used for the key macrocyclization step.diversity | library | stereochemistry | high throughput

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supporting

confidence: 57%

Fragment-based domain shuffling approach for the synthesis of pyran-based macrocycles

Comer

Joliton

et al. 2011

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

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“…Spongistatin 1 (29a) ≈ altohyrtin (29b) ≈ cinachryolide A (29c) is a highly oxygenated polyketidemacrolide isolated in low yield from a collection of diverse marine sponges (Pietruszka 1998;Radjasa et al 2011). With 24 stereocenters and two E,Z-olefins, spongistatin 1 displays tremendous stereochemical complexity.…”

Section: Polyketidementioning

confidence: 99%

An Update on the Biomedical Prospects of Marine‐derived Small Molecules with Fascinating Atom and Stereochemical Diversity

Vaske

Crews

2013

Bioactive Compounds From Marine Foods

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In this chapter we discuss a selection of structurally diverse marine-derived small molecules (MDSMs) with potent and/or specific bioactivity and analyze their biomedical applications. The compounds included have been isolated either from marine macroorganisms, including sponges, ascidians (tunicates), bryozoans, and molluscs, or from microorganisms, such as bacteria and fungi. Our inquiry begins with a look back in time at a selection of important marine natural products, with particular focus on compounds in the clinical pipeline. The chapter continues with an analysis of a biosynthetically diverse assortment of 22 MDSMs and their structural elements of atom and stereochemical diversity. Entries have been divided into five biosynthetic classes: terpene, polyketide, alkaloid, depsipeptide, and polyketide-peptide. Enormous structural variety is represented by the marine natural products treated herein. The compounds selected can be considered to represent case examples of significant biomolecules with positivity and, in some cases, potent bioactivity accompanied by an unusual mechanism of action. Overview of known compounds, highlighting molecules of significanceThe ocean covers more than 70% of the earth's surface and is home to exceptional biodiversity: more than one million marine species and an estimated one billion different kinds of marine microbe (Census of Marine Life Press Release 2010). We and others firmly believe that MDSMs represent a continuing resource for tools important in cell biology research and in the design of the next-generation leads for drug discovery and development. The record to date firmly illustrates that the structures of natural products continue to be invaluable in expanding pharmacophore structural space. For example, Newman and Cragg recently provided a detailed analysis of the last 30 years of natural products in drug discovery, wherein they contended that, "Nature's 'treasure trove of small molecules' remains to be explored, particularly from the marine and microbial environments" (Newman & Cragg 2012).

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“…Their basic mono-or bis-spiroketal framework resembles that found in many relevant natural products, including steroidal saponins, polyether ionophores, macrolide antibiotics, insect pheromones, and toxic metabolites from algae and fungi [1][2][3][4][5], and is the target of much synthetic effort [6][7][8][9][10][11][12][13][14]. DFAs are formed upon thermal and/or acidic activation of sucrose-and/or D-fructose-rich materials.…”

Section: Introductionmentioning

confidence: 99%

Chemical and Enzymatic Approaches to Carbohydrate-Derived Spiroketals: Di-D-Fructose Dianhydrides (DFAs)

et al. 2008

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Di-D-fructose dianhydrides (DFAs) comprise a unique family of stereoisomeric spiro-tricyclic disaccharides formed upon thermal and/or acidic activation of sucroseand/or D-fructose-rich materials. The recent discovery of the presence of DFAs in food products and their remarkable nutritional features has attracted considerable interest from the food industry. DFAs behave as low-caloric sweeteners and have proven to exert beneficial prebiotic nutritional functions, favouring the growth of Bifidobacterium spp. In the era of functional foods, investigation of the beneficial properties of DFAs has become an important issue. However, the complexity of the DFA mixtures formed during caramelization or roasting of carbohydrates by traditional procedures (up to 14 diastereomeric spiroketal cores) makes evaluation of their individual properties a difficult challenge. Great effort has gone into the development of efficient procedures to obtain DFAs in pure form at laboratory and industrial scale. This paper is devoted to review the recent advances in the stereoselective synthesis of DFAs by means of chemical and enzymatic approaches, their scope, limitations, and complementarities.

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Spongistatins, Cynachyrolides, or Altohyrtins? Marine Macrolides in Cancer Therapy

Cited by 62 publications

References 4 publications

Fragment-based domain shuffling approach for the synthesis of pyran-based macrocycles

Fragment-based domain shuffling approach for the synthesis of pyran-based macrocycles

An Update on the Biomedical Prospects of Marine‐derived Small Molecules with Fascinating Atom and Stereochemical Diversity

Chemical and Enzymatic Approaches to Carbohydrate-Derived Spiroketals: Di-D-Fructose Dianhydrides (DFAs)

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