Solid-Phase Synthesis of Thalidomide and Its Analogues

Abstract

A novel solid-phase synthesis of thalidomide and its metabolites and analogues is described. The synthetic strategy involves the coupling of hydroxymethyl polystyrene with phthalic anhydride to form the resin-linked acid. The acid is then reacted with primary amines followed by acid or base treatment to form thalidomide and its analogues with either open or closed phthalimide rings. Most of the analogues are synthesized with high yields (40.3-98.1% in three steps) and purities (92.3-98.9%).

Therapeutic Effects of a Novel Phenylphthalimide Analog for Corneal Neovascularization and Retinal Vascular Leakage

“…The compound 5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (HDID), compound (2,6-Diisopropylphenyl)-isoindole-1,3-dione (DID), and compound (2,6-diisopropylphenyl)-5-amino-1 H -isoindole-1,3-dione (DAID) were synthesized as described previously. 44 …”

“…In the present study, we have designed and synthesized a series of novel phenylphthalimide analogs by substituting the glutarimide ring with an aromatic group. 44 In vitro studies have shown that some of these analogs have antiproliferative and antimitotic activities. 45 Here, we evaluated the antiangiogenic effects of three analogs.…”

Solid-Phase Methods for the Microwave-Assisted Synthesis of Heterocycles

“…It should be noted that protocols using conventional heating [167,168] were found to be unfeasible for large library production, as they required reaction times of several hours. Optimization of microwave-enhanced cyclative cleavage from Wang resin was first investigated through the synthesis of model (Fig.…”

Facile Synthesis of Thalidomide

“…Briefly, among the number of publications on the synthesis of thalidomide, different starting materials such as phthalic anhydride and l -glutamic acid, , phthalic anhydride and l -glutamine, − N -carbethoxy-phthalimide and l -glutamine, − phthalic anhydride and 2,6-dioxo-3-amino-pyridine or its derivatives, , N -phthaloyl- dl -glutamic acid , or N -phthaloyl- dl -glutamic anhydride, , phthalic acid with 2,6-dioxo-3-amino-pyridine, phthalimide and glutamic acid, and other materials − were used. Although these synthesis techniques imply simple changes, there are several weak points with respect to large-scale production: (1) using extravagant starting reagents/materials in the steps related to the preparation; (2) carrying out the reactions at a high temperature requiring multiple recrystallizations or purification by column chromatography on silica gel; (3) using toxic solvents/materials; (4) multistep procedures; , and (5) low overall yields .…”