123237-62-7Relevant academic research and scientific papers
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.
Synthesis and Evaluation of Novel TLR2 Agonists as Potential Adjuvants for Cancer Vaccines
Lu, Benjamin L.,Williams, Geoffrey M.,Verdon, Daniel J.,Dunbar, P. Rod,Brimble, Margaret A.
supporting information, p. 2282 - 2291 (2019/10/02)
Cancer immunotherapy has gained increasing attention due to its potential specificity and lack of adverse side effects when compared to more traditional modes of treatment. Toll-like receptor 2 (TLR2) agonists are lipopeptides possessing the S-[2,3-bis(palmitoyloxy)propyl]-l-cysteine (Pam2Cys) motif and exhibit potent immunostimulatory effects. These agonists offer a means of providing "danger signals" in order to activate the immune system toward tumor antigens. Thus, the development of TLR2 agonists is attractive in the search of potential immunostimulants for cancer. Existing SAR studies of Pam2Cys with TLR2 indicate that the structural requirements for activity are, for the most part, very intolerable. We have investigated the importance of stereochemistry, the effect of N-terminal acylation, and homologation between the two ester functionalities in Pam2Cys-conjugated lipopeptides on TLR2 activity. The R diastereomer is significantly more potent than the S diastereomer and N-terminal modification generally lowers TLR2 activity. Most notably, homologation gives rise to analogues which are comparatively active to the native Pam2Cys containing constructs.
Synthesis of acylglycerol derivatives by mechanochemistry
Ardila-Fierro, Karen J.,Pich, Andrij,Spehr, Marc,Hernández, José G.,Bolm, Carsten
supporting information, p. 811 - 817 (2019/04/17)
In recent times, many biologically relevant building blocks such as amino acids, peptides, saccharides, nucleotides and nucleosides, etc. have been prepared by mechanochemical synthesis. However, mechanosynthesis of lipids by ball milling techniques has remained essentially unexplored. In this work, a multistep synthetic route to access mono- and diacylglycerol derivatives by mechanochemistry has been realized, including the synthesis of diacylglycerol-coumarin conjugates.
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.
Synthesis method of glycerol carbonate
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Paragraph 0041; 0042; 0043, (2017/10/13)
The invention relates to the field of glycerol carbonate, particularly a synthesis method of high-purity glycerol carbonate. According to the method, glycidol is utilized to prepare the high-purity glycerol carbonate. The method comprises the following steps: adding glycidol, triethylamine and dichloromethane into a reaction kettle, performing cooling to 0 DEG C, dropwisely adding a silyl protecting group, recovering to room temperature after the dropwise addition is finished, performing reaction over night, performing washing with water, drying and distillation to obtain silyl-protected glycidol, performing addition reaction with carbon dioxide by using a catalyst to obtain silyl-protected glycerol carbonate, performing deprotection by using an acid, and performing distillation to remove the solvent, thereby obtaining the high-purity glycerol carbonate. The method has the advantages of simple technical operation process, recyclable raw materials, high product purity and low hazard, and is suitable for industrial production.
A versatile route to polythiophenes with functional pendant groups using alkyne chemistry
Huang, Xiao,Yang, Li,Emanuelsson, Rikard,Bergquist, Jonas,Str?mme, Maria,Sj?din, Martin,Gogoll, Adolf
supporting information, p. 2682 - 2688 (2017/01/09)
A new versatile polythiophene building block, 3-(3,4-ethylenedioxythiophene)prop-1-yne (pyEDOT) (3), is prepared from glycidol in four steps in 28% overall yield. pyEDOT features an ethynyl group on its ethylenedioxy bridge, allowing further functionalization by alkyne chemistry. Its usefulness is demonstrated by a series of functionalized polythiophene derivatives that were obtained by pre- and post-electropolymerization transformations, provided by the synthetic ease of the Sonogashira coupling and click chemistry.
Stereochemistry and Mechanism of Undecylprodigiosin Oxidative Carbocyclization to Streptorubin B by the Rieske Oxygenase RedG
Withall, David M.,Haynes, Stuart W.,Challis, Gregory L.
supporting information, p. 7889 - 7897 (2015/07/02)
The prodiginines are a group of specialized metabolites that share a 4-methoxypyrrolyldipyrromethene core structure. Streptorubin B is a structurally remarkable member of the prodiginine group produced by Streptomyces coelicolor A3(2) and other actinobacteria. It is biosynthesized from undecylprodigiosin by an oxidative carbocyclization catalyzed by the Rieske oxygenase-like enzyme RedG. Undecylprodigiosin derives from the RedH-catalyzed condensation of 2-undecylpyrrole and 4-methoxy-2, 2′-bipyrrole-5-carboxaldehyde (MBC). To probe the mechanism of the RedG-catalyzed reaction, we synthesized 2-(5-pentoxypentyl)-pyrrole, an analogue of 2-undecylpyrrole with an oxygen atom next to the site of C-C bond formation, and fed it, along with synthetic MBC, to Streptomyces albus expressing redH and redG. This resulted in the production of the 6′-oxa analogue of undecylprodigiosin. In addition, a small amount of a derivative of this analogue lacking the n-pentyl group was produced, consistent with a RedG catalytic mechanism involving hydrogen abstraction from the alkyl chain of undecylprodigiosin prior to pyrrole functionalization. To investigate the stereochemistry of the RedG-catalyzed oxidative carbocyclization, [7′-2H](7′R)-2-undecylpyrrole and [7′-2H](7′S)-2-undecylpyrrole were synthesized and fed separately, along with MBC, to S. albus expressing redH and redG. Analysis of the extent of deuterium incorporation into the streptorubin B produced in these experiments showed that the pro-R hydrogen atom is abstracted from C-7′ of undecylprodigiosin and that the reaction proceeds with inversion of configuration at C-7′. This contrasts sharply with oxidative heterocyclization reactions catalyzed by other nonheme iron-dependent oxygenase-like enzymes, such as isopenicillin N synthase and clavaminate synthase, which proceed with retention of configuration at the carbon center undergoing functionalization. (Chemical Equation Presented).
Total Syntheses of Perenniporides
Morita, Masao,Ohmori, Ken,Suzuki, Keisuke
supporting information, p. 5634 - 5637 (2015/12/01)
The total syntheses of perenniporide A (1) and related compounds have been achieved. Starting from 1,3,5-trifluorobenzene (9), difluorodienone 6 was obtained by oxidative dearomatization, which served as a platform for the high-pressure cycloaddition and for the introduction of the C3-methoxy group. The synthesis allowed access to the natural congeners 2 and 3, enabling assignment of the absolute structures of these natural products.
Oxidative cyclization of tertiary pentenol derivatives forming 2,5,5-trisubstituted THF rings and the total synthesis of cyclocapitelline
Phillips, Geoffrey A.,Palmer, Cory,Stevens, Andrew C.,Piotrowski, Mathew L.,Dekruyf, Daryl S.R.,Pagenkopf, Brian L.
supporting information, p. 6052 - 6055 (2015/10/28)
The synthesis of 2,5,5-trisubstituted tetrahydrofuran rings was accomplished via the Mukaiyama aerobic oxidative cyclization of tertiary 5-pentenols employing the Co(nmp)2 catalyst. A variety of THFs were formed in moderate to good yield and diastereoselectivity. The method developed herein was successfully applied to an enantioselective total synthesis of cyclocapitelline.
