Combinatorial Chemistry & High Throughput Screening - Volume 5, Issue 3, 2002

A two step synthesis of trifluoromethyl ketones from aldehydes is reported. A combination of polymer-supported reagents and sequestering agents were employed to effect the transformation without the need for chromatographic purification.

Six precursor resins with systematic variation of porous parameters were prepared by suspension polymerisation using specific compositions of divinylbenzene, styrene vinylbenzyl chloride (VBC) and 2- ethylhexan-l-ol (a porogen). Surface areas from N2 sorption and BET analysis were ∼2-170 m2g-1. The VBC content in each case was 38 mol% and these groups were aminated using the sodium salt of trimethylethylene dia Read More

The preparation of molecular libraries of aminomethylbiaryls, allylic amines, and ethanolamines using solution-phase methodology is described. In particular, the use of a solid-supported base reagent (PTBD resin) and strong cation exchange(SCX) resin to effect ‘catch and release’ purification across these diverse libraries is highlighted.

A method for producing tri- and tetrasubstituted ureas from carbamoyl imidazolium salts is presented. Carbamoyl imidazolium salts are prepared from the reaction of N,N'-carbonyldiimidazole (CDI) with secondary amines, followed by alkylation with iodomethane. These stable salts can be stored for extended periods and are effective electrophilic carbamoylation reagents. Primary and secondary amines add to carbamoyl i Read More

Soluble polymers have emerged as viable alternatives to resin supports across the broad spectrum of high-throughput organic chemistry. As the application of these supports become more widespread, issues such as broad-spectrum solubility and loading are becoming limiting factors and therefore new polymers are required to overcome such limitations. This article details the approach made within our group to new solub Read More

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 derivativ Read More

An automated, parallel, solid-phase synthesis and screening strategy using commercially available aryl acetic acids as starting materials has discovered novel, non-peptide CCR1 antagonists (Ki < 100 nM).

An optimized semi-automatic protocol for parallel synthesis of up to 96 peptide nucleic acids (PNA) or PNA-peptide conjugates using Boc-protection strategy has been developed using a robotic system. The approach is illustrated by synthesizing PNA and PNA-peptide libraries varying between 15 and 27 “amino acid” units. The peptides (NLS (nuclear localization signal) or Tat-peptide) were attached to N-terminus of the PNA. The m Read More