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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Fluorous synthesis of substituted sclerotigenin library
Yimin Lu1, Tadamichi Nagashima, Bruhaspathy Miriyala
1Fluorous Technologies, Inc., Pittsburgh, Pennsylvania 15238, USA.
Abstract:
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.
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Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
Primary alcohols are synthesized from primary alkyl halides, and the...

