Synthesis of acid and two of its conformationally-restricted analogs
作者： Mark W. Read , Michael L. Miller , Partha S. Ray
DOI: 10.1016/S0040-4020(98)01060-6
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摘要: Abstract Synthesis of the titled tetrahydropyrimidoazepine-based folate (6a) is described using a regiospecific γ-alkylation reaction between dienolate generated from 3-carboethoxy-N-2,4-dimethoxybenzyl-1,5,6,7-tetrahydro-(1H)-azepin-2-one (33) and methyl 4-formylbenzoate, as key step. The isoxazolinopyrimidoazepine isoxazolopyrimidoazepine-based folates (7a 8a respectively) were also prepared (via intramolecular 1,3-dipolar cycloaddition chemistry) conformationally-restricted analogs 6a. All three compounds potential antitumor agents based on known, structurally related, agent 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF). Both 7a inactive in human colon carcinoma (GC3c1) cell culture assay. Compound 6a, however, was weakly active (IC50 = 2.0 μM) above
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