Solid-phase Organic Synthesis Research Articles

Dendritic Supports in Organic Synthesis

ChemInformVolume 33, Issue 44 p. 258-258 Reviews Dendritic Supports in Organic Synthesis Robertus J. M. Klein Gebbink, Robertus J. M. Klein Gebbink Dep. Met. Mediated Synth., Debye Res. Inst., Utrecht Univ., NL-3584 CH Utrecht, Neth.Search for more papers by this authorCornelis A. Kruithof, Cornelis A. Kruithof Dep. Met. Mediated Synth., Debye Res. Inst., Utrecht Univ., NL-3584 CH Utrecht, Neth.Search for more papers by this authorGerard P. M. Van Klink, Gerard P. M. Van Klink Dep. Met. Mediated Synth., Debye Res. Inst., Utrecht Univ., NL-3584 CH Utrecht, Neth.Search for more papers by this authorGerard Van Koten, Gerard Van Koten Dep. Met. Mediated Synth., Debye Res. Inst., Utrecht Univ., NL-3584 CH Utrecht, Neth.Search for more papers by this author Robertus J. M. Klein Gebbink, Robertus J. M. Klein Gebbink Dep. Met. Mediated Synth., Debye Res. Inst., Utrecht Univ., NL-3584 CH Utrecht, Neth.Search for more papers by this authorCornelis A. Kruithof, Cornelis A. Kruithof Dep. Met. Mediated Synth., Debye Res. Inst., Utrecht Univ., NL-3584 CH Utrecht, Neth.Search for more papers by this authorGerard P. M. Van Klink, Gerard P. M. Van Klink Dep. Met. Mediated Synth., Debye Res. Inst., Utrecht Univ., NL-3584 CH Utrecht, Neth.Search for more papers by this authorGerard Van Koten, Gerard Van Koten Dep. Met. Mediated Synth., Debye Res. Inst., Utrecht Univ., NL-3584 CH Utrecht, Neth.Search for more papers by this author First published: 19 May 2010 https://doi.org/10.1002/chin.200244258AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume33, Issue44November 5, 2002Pages 258-258 RelatedInformation

Polymeric Supports for Solid Phase Organic Synthesis

The choice of polymeric support plays a key role in the success of solid phase methods for the synthesis of organic compounds. In the past decades, numerous efforts have been dedicated to the development of new polymeric materials with improved swelling in water and organic solvents and increased stability under a wide range of reactions conditions for their use in solid phase organic synthesis. Herein, we present a review of these various types of resins and their applications. Keywords: Polymeric Supports, Organic Synthesis, Crosslinked Polystyrene, Rasta Resins

From protein domains to drug candidates-natural products as guiding principles in the design and synthesis of compound libraries.

In the continuing effort to find small molecules that alter protein function and ultimately might lead to new drugs, combinatorial chemistry has emerged as a very powerful tool. Contrary to original expectations that large libraries would result in the discovery of many hit and lead structures, it has been recognized that the biological relevance, design, and diversity of the library are more important. As the universe of conceivable compounds is almost infinite, the question arises: where is a biologically validated starting point from which to build a combinatorial library? Nature itself might provide an answer: natural products have been evolved to bind to proteins. Recent results in structural biology and bioinformatics indicate that the number of distinct protein families and folds is fairly limited. Often the same structural domain is used by many proteins in a more or less modified form created by divergent evolution. Recent progress in solid-phase organic synthesis has enabled the synthesis of combinatorial libraries based on the structure of complex natural products. It can be envisioned that natural-product-based combinatorial synthesis may permit hit or lead compounds to be found with enhanced probability and quality.

SPOCC-194, a new high functional group density PEG-based resin for solid-phase organic synthesis.

A novel polymer matrix for solid-phase synthesis, SPOCC(194) resin (1), was designed featuring a backbone of homogeneous tetraethylene glycol (TEG(194)) macromonomer linked by quaternary carbon junctions and terminating in primary alcohol functionality. Beaded SPOCC(194) resin was effectively prepared by suspension polymerization of oxetanylated TEG macromonomer 5 in stirred silicon oil. Mechanically stable and inert to a diverse range of reaction conditions, SPOCC(194) possessed a high hydroxyl group loading (0.9-1.2 mmol/g) for substrate attachment and swelled effectively ( approximately 2-4 mL/g) in a variety of organic and aqueous solvents. Developed for solid-phase synthesis at high reactant concentrations for driving organic and aqueous reactions to completion, SPOCC(194) exhibited high functional group density (mmol/mL) similar to that of low-loaded aminomethylated polystyrene-divinylbenzene copolymer (PS-1%DVB) yet significantly higher than that of PEGA(1900), SPOCC(1500), and TentaGel S. High-resolution MAS NMR spectra of Fmoc-derivatized SPOCC(194) indicate that monitoring of functional group transformation is possible. Moreover, by employment of a nonaromatic resin-linker combination, electrophilic chemistry, such as Lewis acid catalyzed glycosylation and Friedel-Crafts acylation, was selectively performed on substrate bound to SPOCC(194) resin. Such properties make SPOCC(194) resin a promising new polymer matrix for the support-bound construction of small organic molecules by parallel and combinatorial synthesis and the scavenging of solution-phase reactants or byproducts.

Low dilution procedures in solid-phase organic synthesis: Diels–Alder and Heck reactions

The use of extremely low solvent volumes (2 μL or less per mg resin) results in significant increases in yield for both the Diels–Alder and Heck reactions on solid-phase compared to standard high dilution techniques.

A useful acylation method using trichloroacetonitrile and triphenylphosphine for solid phase organic synthesis

A novel acylation procedure was developed for polymer supported synthesis, with in situ generated acyl chlorides using trichloroacetonitrile and triphenylphosphine.

Synthesis of 4-pentenoic and 5-hexenoic acids on polystyrene resin and their use as cleavable linkers

Direct synthesis of 4-pentenoic and 5-hexenoic acid derivatives on polystyrene resin was achieved and their use as cleavable linkers in solid phase organic synthesis has been demonstrated.

Synthesis of combinatorial libraries based on terpenoid scaffolds.

Triterpenoid-based scaffolds betulinic acid (1a) and ursolic acid (1b), have been used for the generation of combinatorial libraries in parallel format using solid phase organic synthesis method. These templates have the potential for the synthesis and amplification of triterpenoid-based compounds with one and two-point diversity. This has been demonstrated by the synthesis of two small libraries comprising 18 derivatives each of betulinic acid and ursolic acid with structural diversity at C-3 and C-28 positions. The primary screening of antimalarial activity of these libraries against P. falciparum in vitro led to the identification of four compounds with 5 fold increase in the activity compared to betulinic and ursolic acids.

2-(3-Aminopropyl)-4-pentenoic acid as a bio-compatible/cleavable linker for solid-phase organic synthesis

2-(3-Aminopropyl)-4-pentenoic acid lithium salt ( 1 ) was prepared and used as a bio-compatible, cleavable linker in solid-phase organic synthesis. The products were released from solid support through cycloelimination.

Solid-supported reagents for multi-step organic synthesis: preparation and application

Since the early days of combinatorial chemistry solid-phase organic synthesis has been the method of choice for the production of large libraries. Solution-phase synthesis is again gaining importance especially for the synthesis of parallel arrays of smaller, focussed libraries containing single compounds with high degrees of purity. In the field of solution-phase library generation, the use of solid-supported reagents, catalysts and scavengers is emerging as a leading strategy, combining the advantages of both solid-phase organic synthesis (e.g. allowing the employment of an excess of reagent without the need for additional purification steps) and solution-phase chemistry (e.g. the ease of monitoring the progress of the reactions by applying LC-MS, TLC or standard NMR techniques). An account of some of the most recent advances in this area of research will be presented.

Dendritic supports in organic synthesis

An overview is presented of the recent developments in the use of dendritic supports in organic synthesis. Examples are presented of the application of dendritic supports in both liquid- and solid-phase organic synthesis. In liquid-phase synthesis, soluble dendrimers are used as the substrate support, while in solid-phase synthesis, ‘dendronized’ insoluble resins are used for this purpose. Selected examples of the synthesis of compound libraries on dendritic supports via combinatorial techniques are discussed.

Introducing Freshmen Students to the Practice of Solid-Phase Synthesis

Background and Rationale for the Experiment Solid-phase chemistry has revolutionized the synthesis of organic compounds, peptides, oligonucleotides, carbohydrates, drugs, and combinatorial libraries (1‐5). Although many types of compounds incorporating a variety of building blocks can be created, all solid-phase syntheses share a common approach. In a typical synthesis, starting material is anchored to a polymeric support and transformed into product by the action of solution-phase reagents. The product is then liberated into solution. The reverse approach has been used to convert solution-phase reactants into products by means of supportimmobilized reagents and catalysts (6 ). Solid-phase organic synthesis is effective because reagents can be used in excess to drive reactions and immobilized products can be purified by repeated washings (7). In addition, syntheses can be automated. By combining these attractive features, multistep syntheses that would be considered unfeasible under homogeneous solutionphase conditions have been realized. The merit and popularity of solid-phase protocols are illustrated by the example of Bruce Merrifield, who received a Nobel Prize for his seminal contribution, and further, by explosive developments in combinatorial chemistry and drug discovery (5, 8‐11). Our goal was to introduce students in the early stages of academic development to the principles and practice of synthesis. Freshmen students attending a “pick-a-project” course were ideal subjects for the study. Several enrollees had expressed a curiosity in the topic of synthetic chemistry, but clearly lacked the practical experience required to carry out a multistep solution synthesis. As solid-phase methods have proven advantageous, popular, relevant, and technically facile, a project focused on solid-phase synthesis showed promise as an instructional vehicle. Peptide synthesis in particular was chosen because its chemistry has been developed to the point where success is virtually guaranteed if protocols are followed faithfully (2, 12‐14). The novelty of presenting peptide chemistry to freshmen students in a tangible, hands-on fashion rather than by using a textbook approach was also a deciding factor (15). Structure, Content, and Pedagogy Students were asked to write a project proposal, present goals, rationale, and methods to a committee, implement the proposal, document results, and conclude the project in report and oral PowerPoint format before peers and faculty. In addition to instructor guidance and support, the students had intranet access to guidelines on preparing proposals, reports, and oral presentations and to mandatory readings on the subjects of synthesis and analysis (2, 12‐18). Basic chromatography, spectrometry, spectroscopy, kinetics, and enzyme function were discussed, and detailed protocols were supplied to facilitate in-lab instruction. Project objectives were realized by adopting a guided, step-by-step, hands-on approach. The students worked and studied collaboratively in order to promote interactive learning. They were introduced to key concepts with the aid of laboratory demonstrations and visual tools and were encouraged to consolidate these concepts as they implemented the project. The completed project was archived on the intranet for the benefit of future enrollees. Synthesis, Analysis, and Application

Solid-Phase Organic Synthesis and Combinatorial Chemistry: A Laboratory Preparation of Oligopeptides

The principles and practice of solid-phase organic synthesis and combinatorial chemistry are utilized in a laboratory preparation of oligopeptides. A parallel synthesis scheme is used to generate a series of tripeptides. A divergent synthesis scheme is used to prepare two pentapeptides, one of which is leucine enkephalin, a neurotransmitter known to be an analgesic agent.

Synthetic Studies towards Mniopetals (III). Solid Phase Organic Synthesis of a Key Intermediate for Combinatorial Synthesis of Mniopetals, Kuehneromycins and Marasmanes

Synthetic Studies towards Mniopetals (III). Solid Phase Organic Synthesis of a Key Intermediate for Combinatorial Synthesis of Mniopetals, Kuehneromycins and Marasmanes

ChemInform Abstract: Resins and Anchors for Solid Phase Organic Synthesis

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A síntese orgânica em fase sólida e seus suportes poliméricos mais empregados

In the last decade we have seen improved a powerfull tool to medicinal chemistry: the Solid Phase Organic Synthesis (SPOS). This metodology can be used to synthesize a large library of compounds in a short time by combinatorial chemistry, where simple chemical substances can be combinated one to each other building a library of complex compounds. In this work we present the solid phase organic synthesis and their advantage upon the tradicional organic synthesis methodology, as well as the main polimers used in the SPOS technique.

New phenanthridine linkers for the solid-phase synthesis of acid-containing compounds.

Two novel, reusable phenanthridine linkers that use cerium ammonium nitrate as a cleavage reagent are described. These linkers are based on a disubstituted amide and are designed for the release of carboxylic acids but tolerate exposure to acidic, basic, and reductive reaction conditions. Application of these linkers to solid-phase organic synthesis affords products in excellent yields and high purities.

Protecting groups in solid-phase organic synthesis.

ADVERTISEMENT RETURN TO ISSUEReviewNEXTProtecting Groups in Solid-Phase Organic SynthesisDavid Orain, John Ellard, and Mark BradleyView Author Information Department of Chemistry, University of Southampton, Southampton SO17 1BJ, U.K. Cite this: J. Comb. Chem. 2002, 4, 1, 1–16Publication Date (Web):October 20, 2001Publication History Received29 December 2000Published online20 October 2001Published inissue 1 January 2002https://doi.org/10.1021/cc0001093Copyright © 2002 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views7840Altmetric-Citations35LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (202 KB) SUBJECTS:Amines,Organic compounds,Organic polymers,Peptides and proteins,Protective groups Get e-Alerts

Combinatorial approaches in anticancer drug discovery: recent advances in design and synthesis.

Combinatorial technology for the generation of molecular diversity has evolved as an integrated component in accelerated drug discovery process. During the emerging days of combinatorial chemistry, solid-phase organic synthesis has been the leading strategy for the production of large libraries for lead discovery. As combinatorial techniques for the library synthesis has evolved, solution-phase synthesis of smaller, targeted libraries is gaining attention. Numerous syntheses of biologically active chemical libraries of small molecules have been reported during the past decade. This review will focus only on the recent literature of chemical libraries targeted towards anticancer properties. The synthesis, chemistry and biological activity of these libraries as anticancer agents are summarized.

Monitoring of solid-phase organic synthesis on macroscopic supports by high-resolution magic angle spinning NMR.

In this paper we demonstrate the efficiency of high-resolution magic angle spinning NMR to monitor solid-phase organic chemistry on macroscopic systems such as Synphase lanterns. The use of the LED sequence eliminates the peaks due to the use of protonated solvents and was also sufficient to decrease the signals due to the matrix. As a direct result, we established that reaction kinetics on the lantern proved to be significantly more rapid than on an equivalent polystyrene resin. More generally, the macroscopic nature of the support facilitates both sample preparation and spectral recording and hence opens up the perspective of an automated on-line analysis in combinatorial chemistry.