Allen Kesselring - Academia.edu (original) (raw)

Uploads

Papers by Allen Kesselring

Research paper thumbnail of ChemInform Abstract: Preparation of Small Molecule Libraries for Agrochemical Discovery. Development of Parallel Solution and Solid Phase Synthesis Methods

Research paper thumbnail of Parallel Solid-Phase Synthesis and High-Throughput 1 H NMR Evaluation of a 96-Member 1,2,4-Trisubstituted-pyrimidin-6-one-5-carboxylic Acid Library

Journal of Combinatorial Chemistry, 2009

A solid-phase organic synthesis method has been developed for the preparation of trisubstituted p... more A solid-phase organic synthesis method has been developed for the preparation of trisubstituted pyrimidin-6-one carboxylic acids 12, which allows elaboration to a 3-dimensional combinatorial library. Three substituents are introduced by initial Knoevenagel condensation of an aldehyde and malonate ester resin 7 to give resin bound 1. Cyclization of 1 with an N-substituted amidine 10, oxidation, and cleavage afforded pyrimidinone 12. The initial solid-phase reaction sequence was followed by gel-phase 19 FNMR and directcleavage 1 H NMR of intermediate resins to determine the optimal conditions. The scope of the method for library production was determined by investigation of a 3 × 4 pilot library of twelve compounds. Cyclocondensation of N-methylamidines and 7 followed by CAN oxidation gave mixtures of the resin bound pyrimidin-6-one 11 and the regioisomeric pyrimidin-4-one 15, which after cleavage from the resin afforded a nearly 1:1 mixture of pyrimidin-6-one and pyrimidin-4-one carboxylic acids 12 and 16, respectively. The regiochemical assignment was confirmed by ROESY1D and gHMBC NMR experiments. A library was prepared using 8 aldehydes, 3 nitriles, and 4 amines to give a full combinatorial set of 96 pyrimidinones 12. Confirmation of structural identity and purity was carried out by LCMS using coupled ELS detection and by high-throughput flow 1 H NMR.

Research paper thumbnail of High-Throughput 1 H NMR and HPLC Characterization of a 96-Member Substituted Methylene Malonamic Acid Library

Journal of Combinatorial Chemistry, 1999

A solid phase organic synthesis method has been developed for the preparation of substituted meth... more A solid phase organic synthesis method has been developed for the preparation of substituted methylene malonamic acids and malonic ester mono acids 5. Two substituents are introduced into the core molecule 5 by preparation of unsymmetrical malonic acid ...

Research paper thumbnail of ChemInform Abstract: Preparation of Small Molecule Libraries for Agrochemical Discovery. Development of Parallel Solution and Solid Phase Synthesis Methods

Research paper thumbnail of Parallel Solid-Phase Synthesis and High-Throughput 1 H NMR Evaluation of a 96-Member 1,2,4-Trisubstituted-pyrimidin-6-one-5-carboxylic Acid Library

Journal of Combinatorial Chemistry, 2009

A solid-phase organic synthesis method has been developed for the preparation of trisubstituted p... more A solid-phase organic synthesis method has been developed for the preparation of trisubstituted pyrimidin-6-one carboxylic acids 12, which allows elaboration to a 3-dimensional combinatorial library. Three substituents are introduced by initial Knoevenagel condensation of an aldehyde and malonate ester resin 7 to give resin bound 1. Cyclization of 1 with an N-substituted amidine 10, oxidation, and cleavage afforded pyrimidinone 12. The initial solid-phase reaction sequence was followed by gel-phase 19 FNMR and directcleavage 1 H NMR of intermediate resins to determine the optimal conditions. The scope of the method for library production was determined by investigation of a 3 × 4 pilot library of twelve compounds. Cyclocondensation of N-methylamidines and 7 followed by CAN oxidation gave mixtures of the resin bound pyrimidin-6-one 11 and the regioisomeric pyrimidin-4-one 15, which after cleavage from the resin afforded a nearly 1:1 mixture of pyrimidin-6-one and pyrimidin-4-one carboxylic acids 12 and 16, respectively. The regiochemical assignment was confirmed by ROESY1D and gHMBC NMR experiments. A library was prepared using 8 aldehydes, 3 nitriles, and 4 amines to give a full combinatorial set of 96 pyrimidinones 12. Confirmation of structural identity and purity was carried out by LCMS using coupled ELS detection and by high-throughput flow 1 H NMR.

Research paper thumbnail of High-Throughput 1 H NMR and HPLC Characterization of a 96-Member Substituted Methylene Malonamic Acid Library

Journal of Combinatorial Chemistry, 1999

A solid phase organic synthesis method has been developed for the preparation of substituted meth... more A solid phase organic synthesis method has been developed for the preparation of substituted methylene malonamic acids and malonic ester mono acids 5. Two substituents are introduced into the core molecule 5 by preparation of unsymmetrical malonic acid ...

Log In