124150-87-4Relevant articles and documents
Studies toward the Synthesis of an Oxazole-Based Analog of (-)-Zampanolide
Bold, Christian P.,Klaus, Cindy,Pfeiffer, Bernhard,Schurmann, Jasmine,Lombardi, Rafael,Lucena-Agell, Daniel,Diaz, J. Fernando,Altmann, Karl-Heinz
, p. 2238 - 2242 (2021/04/05)
Studies are described toward the synthesis of an oxazole-based analog of (-)-zampanolide (2). Construction of (-)-dactylolide analog 22 was achieved via alcohol 5 and acid 4 through esterification and Horner-Wadsworth-Emmons (HWE)-based macrocyclization; however, attempts to attach (Z,E)-sorbamide to 22 proved unsuccessful. The C(8)-C(9) double bond of the macrocycle was prone to migration into conjugation with the oxazole ring, which may generally limit the usefulness of zampanolide analogs with aromatic moieties as tetrahydropyran replacements.
Characterization of novel kainic acid analogs as inhibitors of select microglial functions
Alford, Morgan A.,Tian, Zhenlin,Menard, Frederic,Klegeris, Andis
, p. 25 - 35 (2019/03/04)
Alzheimer's disease (AD) is characterized by abnormal accumulation of extracellular amyloid beta protein (Aβ) plaques and intracellular neurofibrillary tangles, as well as by a state of chronic inflammation in the central nervous system (CNS). Adverse activation of microglia, the brain immune cells, is believed to contribute to AD pathology including excessive neuronal death. Thus, normalizing immune functions of microglia could slow neurodegeneration, and identification of novel compounds capable of modifying microglial functions is an important goal. Since kainic acid (KA) has been shown to modulate microglial morphology and immune functions, we synthesized six new KA analogs (KAAs) and tested their effects on select microglial functions by using three different cell types as microglia models. Four of the KAAs at low micromolar concentrations inhibited secretion of cytotoxins, monocyte chemoattractant protein (MCP)?1, reactive oxygen species and nitric oxide (NO) by immune-stimulated microglia-like cells. We hypothesize that the effects of the novel KAAs on microglia-like cells are not mediated by KA receptors since their biological activity was distinct from that of KA in all assays performed. A structural similarity search identified aldose reductase (AR) as a potential target for the novel KAAs. This hypothesis was supported by use of AR inhibitor zopolrestat, which abolished the inhibitory effects of two KAAs on microglial secretion of NO. Since the newly developed KAAs inhibited pro-inflammatory and cytotoxic functions of microglia, they should be further investigated for their potential beneficial effect on neuroinflammation and neurodegeneration in AD animal models.
Total Synthesis of (?)-Histrionicotoxin through a Stereoselective Radical Translocation–Cyclization Reaction
Sato, Manabu,Azuma, Hiroki,Daigaku, Akihiro,Sato, Sota,Takasu, Kiyosei,Okano, Kentaro,Tokuyama, Hidetoshi
supporting information, p. 1087 - 1091 (2017/01/18)
Stereoselective total syntheses of (?)-histrionicotoxin and (?)-histrionicotoxin 235A are described. The 1-azaspiro[5.5]undecane skeleton was constructed diastereoselectively by a radical translocation–cyclization reaction involving a chiral cyclic acetal; the use of tris(trimethylsilyl)silane was crucial for the high diastereoselectivity. The cyclization product was converted into (?)-histrionicotoxin 235A through a one-pot partial-reduction–allylation reaction of a derivative containing an unprotected lactam. Finally, two terminal alkenes were transformed into enynes with the 1,3-amino alcohol protected as an oxathiazolidine oxide to complete the total synthesis of (?)-histrionicotoxin.
