Large Scale Preparation of Silicon-Functionalized SynPhase Polystyrene Lanterns for Solid-Phase Synthesis

Ryba, Troy D.; Depew, Kristopher M.; Marcaurelle, Lisa A.

doi:10.1021/cc8000986

Cited by 13 publications

(20 citation statements)

References 15 publications

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“…Namely, PMB removal was required to provide a primary alcohol for loading onto solid-support, while adjustment of the nitrogen protecting groups was needed to ensure compatibility with our silicon-based linker once immobilized onto solid-support 46,47. To illustrate the necessary protecting group manipulations, we selected one diastereomer from each pairing reaction to advance to the final library scaffold.…”

Section: Resultsmentioning

confidence: 99%

An Aldol-Based Build/Couple/Pair Strategy for the Synthesis of Medium- and Large-Sized Rings: Discovery of Macrocyclic Histone Deacetylase Inhibitors

et al. 2010

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An aldol-based ‘build/couple/pair’ (B/C/P) strategy was applied to generate a collection of stereochemically and skeletally diverse small molecules. In the build phase, a series of asymmetric syn- and anti- aldol reactions were performed to produce four stereoisomers of a Boc protected γ-amino acid. In addition both stereoisomers of O-PMB-protected alaninol were generated to provide a chiral amine coupling partner. In the couple step, eight stereoisomeric amides were synthesized by coupling the chiral acid and amine building blocks. The amides were subsequently reduced to generate the corresponding secondary amines. In the pair phase, three different reactions were employed to enable intramolecular ring-forming processes, namely: nucleophilic aromatic substitution (SNAr), Huisgen [3+2] cycloaddition and ring-closing metathesis (RCM). Despite some stereochemical dependencies, the ring-forming reactions were optimized to proceed with good to excellent yields providing a variety of skeletons ranging in size from 8- to 14-membered rings. Scaffolds resulting from the RCM pairing reaction were diversified on solid-phase to yield a 14,400-membered library of macrolactams. Screening of this library led to the discovery of a novel class of histone deacetylase inhibitors, which display mixed enzyme inhibition and led to increased levels of acetylation in a primary mouse neuron culture. The development of stereo-structure/activity relationships (SSAR) was made possible by screening all 16 stereoisomers of the macrolactams produced through the aldol-based B/C/P strategy.

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Section: Resultsmentioning

confidence: 99%

An Aldol-Based Build/Couple/Pair Strategy for the Synthesis of Medium- and Large-Sized Rings: Discovery of Macrocyclic Histone Deacetylase Inhibitors

et al. 2010

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“…Moreover, the reactions on solid support may be staggered, with several reports in the literature of large-scale synthesis. 83 For instance, the industrial peptide synthesis is carry out on solidphase and can be adapted to synthesis of small compounds. Also, this technology can be extended to solution phase synthesis with the employment of polymer-support reagents, catalysts, and cleanup agents (scavengers), which facilitate reactions of substrates in solution.…”

Section: Discussionmentioning

confidence: 99%

Highlights in the solid-phase organic synthesis of natural products and analogues

Eifler‐Lima¹,

Graebin²,

Uchôa³

et al. 2010

J. Braz. Chem. Soc.

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Neste trabalho nós apresentamos uma revisão sobre a síntese em fase sólida de metabólitos secundários, tais como alcalóides, poliaminas, esteróides, terpenos e flavonóides, descritos na literatura a partir de 2000. Um número considerável de rotas sintéticas elegantes e desafiadoras, usando suportes sólidos, será discutido.In this manuscript, we disclose solid-phase organic syntheses (SPOS) of small-molecules of some secondary metabolites, such as alkaloids, polyamines, steroids, terpenes, and flavonoids, described in the literature since 2000. A number of elegant, efficient and challenging syntheses on solid support will be presented.

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“…SynPhase Lanterns appeared to be the support of choice for diversity-oriented synthesis (DOS) of drug-like molecules, and they were reportedly used for syntheses of over 300,000 DOS compounds. 113 OTHER FORMULATIONS. Another form of solid support is monolithic disks.…”

Section: Strategies In Combinatorial Solid-phase Synthesismentioning

confidence: 99%

Practical Aspects of Combinatorial Solid‐Phase Synthesis

Hlaváč¹,

Soural²,

Krchňák³

2011

Solid‐Phase Organic Synthesis

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Large Scale Preparation of Silicon-Functionalized SynPhase Polystyrene Lanterns for Solid-Phase Synthesis

Cited by 13 publications

References 15 publications

An Aldol-Based Build/Couple/Pair Strategy for the Synthesis of Medium- and Large-Sized Rings: Discovery of Macrocyclic Histone Deacetylase Inhibitors

An Aldol-Based Build/Couple/Pair Strategy for the Synthesis of Medium- and Large-Sized Rings: Discovery of Macrocyclic Histone Deacetylase Inhibitors

Highlights in the solid-phase organic synthesis of natural products and analogues

Practical Aspects of Combinatorial Solid‐Phase Synthesis

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