Solid phase synthesis of chiral 3-substituted quinazoline-2,4-diones

Synthesis of 3-N-Sugar-substituted-2, 4(1H,3H)-quinazolinedionesas Anti-Angiogenesis Agents

“…The aminosugars were prepared by the reported method [19]. The general synthesis of the key 2-nitro-( N -sugar-substituted) benzamide intermediates was readily performed by the condensation of 2-nitrobenzoic acid and unprotected aminosugars with EDC(DCC)/HOBt [20,21] (Scheme 1). After formation of amides, the sugar hydroxyl groups were fully acetyled by Ac 2 O/pyridine at room temperature, and then the nitro group was smoothly reduced by powdered Zn in acetic acid/THF.…”

“…After formation of amides, the sugar hydroxyl groups were fully acetyled by Ac 2 O/pyridine at room temperature, and then the nitro group was smoothly reduced by powdered Zn in acetic acid/THF. Finally, cyclization with triphosgene in CH 2 Cl 2 (or ClCH 2 CH 2 Cl) was performed to produce the target molecules [20,21]. …”

“…It was reported that the unprotected amino-sugars could be used directly to synthesize related amides [20,21], and following this method, the key N -sugar o-nitrobenzamide intermediates were obtained with isolated yields of 40-47%.…”

Nucleophile Cleavable Linker Units

“…The same p-nitrophenyl carbonate resin 78 was previously used for the solid-phase synthesis of quinazoline-2,4-diones [112] via N -terminal amino group linkage to the solid support and a base catalysed cyclisation/cleavage strategy used for the synthesis of dipeptides and hydantoins 211 too (Scheme 3.52). [113] A more recent example, concerning the synthesis of pyrazolones, involved a hydrazide linker 211 (Scheme 3.53).…”

(2-Amino-phenyl)-amides of ω-substituted alkanoic acids as new histone deacetylase inhibitors

“…Reaction of isatoic anhydride (25) with 6-aminohexanoic acid followed by consecutive treatment of the resultant reaction mixture with methyl chloroformate and then a base afforded quinazolinedione 30. 16 This material upon alkylation with methyl iodide followed by reaction with an alkali led to 29. Both acids 30 and 29 were coupled in the usual manner to form compounds 28c and 28d.…”