Tadamichi Nagashima

Fluorous electrophilic scavengers for solution-phase parallel synthesis

Abstract A fluorous isatoic anhydride and isocyanate are synthesized and used as scavengers for amines in solution-phase parallel synthesis of urea, thiourea, and β-hydroxyamine analogs. The resulting fluorous derivatives are readily separated from the reaction mixture by solid-phase extractions (SPE) over Fluoro Flash ™ cartridges to give products with good purity. The SPE cartridges can be reused.

Efficient Assembly of Iminodicarboxamides by a “Truly” Four-Component Reaction†

A truly 4-component reaction! In analogy to a galaxy consisting of millions of stars a multicomponent reaction scaffold can result in millions of compound variations. The MCR of α-amino acids, oxocomponents, isocyanides and primary or secondary amines is such a high-number high-diversity reaction providing an enormous potential for drug discovery or catalyst screening.

Fluorous Synthesis of Substituted Sclerotigenin Library

A fluorous linker-assisted synthetic protocol has been developed for preparation of sclerotigenin-type benzodiazepine-quinazolinone library containing 144 analogues. Amide coupling of fluorous trimethoxybenzyl (TMB)-protected amino esters with anthranilic acids followed by base-promoted cyclizations afforded 4-benzodiazepine-2,5-diones. Further derivatization of benzodiazepinediones by reacting with azidobenzoyl chlorides, cyclization, and fluorous linker cleavage afforded the desired compound library. The reaction intermediates were purified by fluorous solid-phase extraction (F-SPE) and final products were further purified by prep-HPLC.