Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Spokane, WA 99201, United States.
Arkansas College of Osteopathic Medicine, Fort Smith, AR 72916, United States.
Bioorg Med Chem Lett. 2018 Feb 15;28(4):562-565. doi: 10.1016/j.bmcl.2018.01.052. Epub 2018 Feb 1.
The multiple-step, one-pot procedure for a series of 2-substituted-3-phosphono-1-thia-4-aza-2-cyclohexene-5-carboxylates, analogues of the natural, sulfur amino acid metabolite lanthionine ketimine (LK), its 5-ethyl ester (LKE) and 2-substituted LKEs is described. Initiating the synthesis with the Michaelis-Arbuzov preparation of α-ketophosphonates allows for a wide range of functional variation at the 2-position of the products. Nine new compounds were synthesized with overall yields range from 40 to 62%. In addition, the newly prepared 2-isopropyl-LK-P, 2-n-hexyl-LKE-P and 2-ethyl-LKE were shown to stimulate autophagy in cultured cells better than that of the parent compound, LKE.
一系列 2-取代-3-膦酸-1-硫代-4-氮杂-2-环己烯-5-羧酸酯的多步一锅法，是天然含硫氨基酸代谢产物硫代高丝氨酸酮亚胺（LK）、其 5-乙酯（LKE）和 2-取代 LKE 的类似物。该合成以 Michaelis-Arbuzov 法制备α-酮膦酸酯为起始，使产物的 2-位具有广泛的功能变化。用此方法合成了 9 种新化合物，总收率为 40%至 62%。此外，新制备的 2-异丙基-LK-P、2-正己基-LKE-P 和 2-乙基-LKE 在培养细胞中诱导自噬的能力优于母体化合物 LKE。
