Solid phase synthesis of complex natural products and libraries thereof

Nicolaou, K. C.; Pfefferkorn, Jeffrey A.

doi:10.1002/1097-0282(2001)60:3<171::aid-bip10030>3.0.co;2-m

Cited by 41 publications

(17 citation statements)

References 69 publications

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“…Combinatorial and diversityoriented synthesis of monovalent molecules has facilitated the discovery of low molecular weight ligands that are optimally designed to bind to a target receptor. [168][169][170][171][172][173] Similarly, libraries of multivalent ligands might be expected to contain compounds that possess diverse activities. [119][120][121]166,167,174] However, the potential diversity of multivalent materials is great and strategies to synthesize diverse collections of multivalent ligands are only beginning to emerge.…”

Section: 3g Combinatorial Multivalent Ligand Synthesis-one New Fromentioning

confidence: 99%

Synthetic Multivalent Ligands as Probes of Signal Transduction

2006

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Cell surface receptors acquire information from the extracellular environment and coordinate intracellular responses. Evidence from biochemical and structural studies indicates that many receptors do not operate as individual entities, but rather as part of higher-order complexes (e.g. dimers and oligomers). Coupling the functions of multiple receptors may endow signaling pathways with the sensitivity and malleability required to govern cellular responses. Moreover, multireceptor signaling complexes may provide a means of spatially segregating otherwise degenerate signaling cascades. Despite the proposed importance of receptor-receptor processes in cellular signaling, questions concerning the mechanisms, extent, and consequences of receptor co-localization and interreceptor communication remain unanswered.Chemical synthesis can provide a variety of compounds with which to address the role of receptor assembly in signal transduction. The focus of this review is one such approach -the use of synthetic multivalent ligands to characterize receptor function. Multivalent ligands can be generated that possess a variety of sizes, shapes, valencies, orientations, and densities of binding elements. Their unique architectures imbue multivalent ligands with the ability to access binding modes not available to monovalent compounds. Multivalent ligands, therefore, are capable of illuminating aspects of inter-receptor processes that are not readily probed using conventional approaches. We suggest that, as focus shifts from investigations of the function of individual proteins and toward the analysis of multi-receptor signaling complexes, multivalent ligands will become even more valuable tools with which to ask sophisticated mechanistic questions. Further, multivalent ligands may provide new opportunities for manipulating receptor systems for the deconvolution of pathways, diagnosis, and, ultimately, the treatment of disease.

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Section: 3g Combinatorial Multivalent Ligand Synthesis-one New Fromentioning

confidence: 99%

Synthetic Multivalent Ligands as Probes of Signal Transduction

2006

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“…These are probably the most diverse activities yet shown from a single-base natural product structure, and it will be very interesting to see how many more biological results will be reported from these series in due course. The potential for such synthetic strategies is further exemplified by another review from the same group that expands the natural products under consideration to polysaccharides, the eleutherobin/sarcodictyin derivatives, and glycopeptide antibiotics such as vancomycin and epothilones [38]. All of these can be considered to be part of the collection of privileged structures.…”

Section: Diversity-oriented Synthesismentioning

confidence: 99%

Interplay between the Chemical Space and the Biological Space

Wang

Ding²,

Zhang

et al. 2012

Organic Chemistry – Breakthroughs and Perspectives

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“…As examples of the pervasiveness of the approach in synthetic organic chemistry, two reviews, one on multiple approaches to traceless supports [42] for SPS and the other on heterocyclic chemistry [43], have recently appeared. Synthesis of complex natural products as diverse as sarcodictylins, chalcones and epothilones [44] utilizing solid-phase organic chemistry are becoming more commonplace as the advantages of a filterable, polymeric protecting group become more widely recognized. The paradigm shift has even extended to the search for metal-binding ligands, catalysts and new materials [45,46].…”

Section: From 1984 To the Presentmentioning

confidence: 99%

Solid‐phase synthesis: a paradigm shift

Marshall

2003

Journal of Peptide Science

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A personal review by the first graduate student of Professor R. Bruce Merrifield of the evolution of solid-phase synthesis and its acceptance by various subsets of the chemistry community. Solid-phase synthesis, as currently practised in the synthesis of biopolymers, combinatorial solid-phase organic chemistry, synthesis of natural products, catalyst selection, chemical ligation and materials development, has proven a paradigm shift for the chemistry community.

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Solid phase synthesis of complex natural products and libraries thereof

Cited by 41 publications

References 69 publications

Synthetic Multivalent Ligands as Probes of Signal Transduction

Synthetic Multivalent Ligands as Probes of Signal Transduction

Interplay between the Chemical Space and the Biological Space

Solid‐phase synthesis: a paradigm shift

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