Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN 55812, USA.
Anticancer Agents Med Chem. 2013 Dec;13(10):1514-30. doi: 10.2174/18715206113139990097.
Alkylation of α-amino acid derived iminoesters with Baylis-Hillman (BH) reaction template based allyl bromides/allyl acetates followed by acidic hydrolysis furnished α-methylene-β-substituted-pyroglutamates and α-alkylidene pyroglutamates respectively. Application of these methodologies has been demonstrated in the synthesis of fused [3.2.0]-γ-lactam-β-lactones. Further, substrate controlled stereoselective alkylation of L-threonine derived oxazoles with BH reaction based allyl bromides and acetates yielded optically pure α-methylene-β-substituted pyroglutamates, and α-alkylidene pyroglutamates. These methodologies have been applied in the preparation of chiral [3.2.0] heterobicyclic pyroglutamates containing hydroxyethyl side chain. All the synthesized pyroglutamates have been evaluated for their anti-cancer and enzyme proteasome inhibition activity.
α-氨基酸亚氨基酯与 Baylis-Hillman（BH）反应模板的烯丙基溴/烯丙基乙酸酯进行烷基化，然后进行酸性水解，分别得到α-亚甲基-β-取代-吡咯烷酮酸和α-亚烷基吡咯烷酮酸。这些方法已应用于稠合[3.2.0]-γ-内酰胺-β-内酰胺的合成中。此外，通过 BH 反应的烯丙基溴和乙酸酯对 L-苏氨酸衍生的恶唑进行底物控制的立体选择性烷基化，得到光学纯的α-亚甲基-β-取代的吡咯烷酮酸和α-亚烷基吡咯烷酮酸。这些方法已应用于制备含有羟乙基侧链的手性[3.2.0]杂双环吡咯烷酮酸。所有合成的吡咯烷酮酸都已评估其抗癌和酶蛋白酶体抑制活性。
