Multiple-step, one-pot synthesis of 2-substituted-3-phosphono-1-thia-4-aza-2-cyclohexene-5-carboxylates and their corresponding ethyl esters

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:28

Article

Shen, Dunxin¹  Hensley, Kenneth²  Denton, Travis T.¹ 

[1] Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Spokane, WA 99201 USA

[2] Arkansas Coll Osteopath Med, Ft Smith, AR 72916 USA

关键词: Autophagy;    Lanthionine ketimine;    Neurodegenerative diseases;    ALS;    Alzheimer's;    Cysteine;    Phosphonate;    Arbuzov;   

DOI  :  10.1016/j.bmcl.2018.01.052

来源: Elsevier

【 摘 要 】

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 alpha-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. (C) 2018 Elsevier Ltd. All rights reserved.

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