4-Aminocyclopentane-1,3-diols as platforms for diversity: synthesis of a screening library

Zohrabi-Kalantari, Vida; Wilde, Felix; Grünert, Renate; Bednarski, Patrick J.; Link, Andreas

doi:10.1039/c3md00252g

Cited by 5 publications

(3 citation statements)

References 19 publications

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“…Reagent alcohol (97% ethanol + methanol) and hexanes were purchased from BDH and were used as received. Grubbs third-generation catalyst (G3) and 3-cyclopenten-1-ol (3CPOH) were synthesized according to previous literature. Toluene, DCM, THF, and diethyl ether were obtained from an SG Waters glass contour solvent purification system that was packed with neutral alumina, and the solvents were passed through a 2 μm filter before being dispensed.…”

Section: Methodsmentioning

confidence: 99%

Variable Temperature ROMP: Leveraging Low Ring Strain Thermodynamics To Achieve Well-Defined Polypentenamers

Neary

Kennemur

2017

Macromolecules

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Living-like conditions through ring-opening metathesis polymerization (ROMP) of low ring strain monomers were achieved through temperature variation during the reaction. For a variety of solvents and readily available ruthenium-based catalysts, warm initiation to low conversions followed by immediate thermal quenching and subsequent propagation to high conversions produced polycyclopentene with molar masses close to theoretical and with moderately low dispersities (Đ ≤ 1.3 ± 0.1). Optimization using Grubbs first-generation catalyst and THF as the solvent consistently resulted in narrow dispersities (<1.2) at various molar masses targeted which increased linearly with monomer-to-catalyst ratio. In all cases, intermolecular chain transfer reactions were suppressed at colder temperatures as evidenced by low dispersity for up to 300 min at 0 °C. This approach was extended to 3-cyclopentenol to emphasize the universality of the methodology to other low ring strain monomers with functional group tolerance specific to Ru-based catalysts.

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Section: Methodsmentioning

confidence: 99%

Variable Temperature ROMP: Leveraging Low Ring Strain Thermodynamics To Achieve Well-Defined Polypentenamers

Neary

Kennemur

2017

Macromolecules

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“…The strategy to synthesize our targeted monomer, 3-cyclopentenyl α-bromoisobutyrate (CPBIB), is shown in Scheme . Monoepoxidization of cyclopentadiene using peroxyacetic acid followed by reduction to 3-cyclopentenol (3CPOH) is straightforward with acceptable yields (∼50% over both steps) . The homoallylic alcohol was esterified using α-bromoisobutyryl bromide (BIBB) to produce CPBIB in good yield (93%).…”

mentioning

confidence: 99%

“…Monoepoxidization of cyclopentadiene using peroxyacetic acid followed by reduction to 3-cyclopentenol (3CPOH) is straightforward with acceptable yields (∼50% over both steps). 88 The homoallylic alcohol was esterified using αbromoisobutyryl bromide (BIBB) 89 to produce CPBIB in good yield (93%). The α-bromoisobutyrate (BIB) group is a workhorse initiator used in atom transfer radical polymerizations (ATRP), which would allow subsequent grafting after VT-ROMP.…”

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confidence: 99%

Well-Defined and Precision-Grafted Bottlebrush Polypentenamers from Variable Temperature ROMP and ATRP

2018

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Polypentenamer macroinitiators are synthesized through variable temperature ring opening metathesis polymerization of 3-cyclopentenyl α-bromoisobutyrate, which has sufficient ring strain (ΔH p = −22.6 kJ mol −1 ) to produce targeted molar mass (<5% from theoretical), low dispersity (1.17 ≤ Đ ≤ 1.23), and high conversion (∼72%). An initiation site for atom-transfer radical polymerization at every fifth backbone carbon allows "grafting-from" of styrene with quantitative initiation and linear molar mass increase with time. These bottlebrushes retain a low dispersity (Đ ≤ 1.34) at varying graft degrees of polymerization (5 ≤ N sc ≤ 49) and have a glass transition temperature highly sensitized to graft length. Extension of the grafts with methyl methacrylate produces a core−shell brush polymer with high molar mass (>1000 kg mol −1 ) and Đ = 1.33. This system exhibits high synthetic versatility and control with a unique flexible backbone to expand the suite of densely grafted polymers.

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Tractable synthesis of multipurpose screening compounds with under-represented molecular features for an open access screening platform

et al. 2014

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The layout of multipurpose screening libraries must address criteria for the compounds such as novelty, diversity potential, innovative design, and last but not least synthetic tractability. While academic compound collections are often innovative, novel, and highly divers, synthesis of analogs or larger substance quantities is often hampered by complex multistep syntheses with low overall yields. In addition, covalently binding compounds and interaction motifs designed to bind metal ions were discriminated against by the paradigm that these interaction types must almost inevitably lead to toxic effects. We would like to challenge this hypothesis. The lack of such interactions could be a reason for frequent failure in the disclosure of hits for hitherto undruggable target proteins using commercially available screening collections. Thus, easily synthesizable screening candidates equipped to bind covalently to nucleophiles or to metalloenzymes by chelation are under-represented in public access screening libraries. Within this work, we present the synthesis and deposition of 88 compounds with five distinct functional classes, each of which features under-represented screening motifs, for example, metal ion complexation, reversible covalent binding, or halogen bonding. The collection includes acetohydrazides, acylhydrazones, propylene glycol ethers, 2-cyanoacetamides, and 2-cyanoacrylamides. The rational for the synthesis of most of the compounds was recently published by our group and is now supplemented by additional compounds reported here for the first time. The public access disposition enables academic research groups to collectively expand the druggable space and interdisciplinary collaborate within the scientific field.

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4-Aminocyclopentane-1,3-diols as platforms for diversity: synthesis of a screening library

Cited by 5 publications

References 19 publications

Variable Temperature ROMP: Leveraging Low Ring Strain Thermodynamics To Achieve Well-Defined Polypentenamers

Variable Temperature ROMP: Leveraging Low Ring Strain Thermodynamics To Achieve Well-Defined Polypentenamers

Well-Defined and Precision-Grafted Bottlebrush Polypentenamers from Variable Temperature ROMP and ATRP

Tractable synthesis of multipurpose screening compounds with under-represented molecular features for an open access screening platform

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