3095-95-2Relevant academic research and scientific papers
Synthesis of phosphonoacetate analogues of the second messenger adenosine 5′-diphosphate ribose (ADPR)
Baszczyňski, Ond?ej,Watt, Joanna M.,Rozewitz, Monika D.,Fliegert, Ralf,Guse, Andreas H.,Potter, Barry V. L.
, p. 1776 - 1785 (2020)
Adenosine 5′-diphosphate ribose (ADPR) is an intracellular signalling molecule generated from nicotinamide adenine dinucleotide (NAD+). Synthetic ADPR analogues can shed light on the mechanism of activation of ADPR targets and their downstream effects. Such chemical biology studies, however, are often challenging due to the negatively charged pyrophosphate that is also sensitive to cellular pyrophosphatases. Prior work on an initial ADPR target, the transient receptor potential cation channel TRPM2, showed complete pyrophosphate group replacement to be a step too far in maintaining biological activity. Thus, we designed ADPR analogues with just one of the negatively charged phosphate groups removed, by employing a phosphonoacetate linker. Synthesis of two novel phosphonoacetate ADPR analogues is described via tandem N,N′-dicyclohexylcarbodiimide coupling to phosphonoacetic acid. Neither analogue, however, showed significant agonist or antagonist activity towards TRPM2, underlining the importance of a complete pyrophosphate motif in activation of this particular receptor.
Composition comprising a phenylalanine-chloroquine derivative as an active ingredient for preventing and treating malaria infection
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Paragraph 0090; 0091; 0093; 0156-0158, (2018/07/28)
The present invention relates to a composition, comprising a phenylalanine-chloroquine derivative compound, represented by a general formula (I), with a novel structure or a pharmacologically acceptable salt as an active ingredient, for treating and preventing malaria. As a result of identification of anti-malaria activity through a search (experiment example 1) for an anti-malaria effect in vitro by using a strain of Plasmodium falciparum and an animal test (experiment example 2) using a mouse infected from malaria with respect to phenylalanine-chloroquine derivative compounds with novel structures, the novel compounds have been identified to have excellent anti-malaria activity. Accordingly, an anti-malaria agent comprising a phenylalanine-chloroquine derivative compound with a novel structure or a pharmacologically acceptable salt as an active ingredient is provided.COPYRIGHT KIPO 2018
Composition comprising a chloroquinoline based α,β-unsaturated amide derivative as an active ingredient for preventing and treating malaria infection
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Paragraph 0090-0093, (2017/02/28)
The present invention relates to an antimalarial agent containing a chloroquine-based andalpha;,andbeta;-unsaturated amide derivative compound having a novel structure as an active component. According to the present invention, an experiment, in order to analyze antimalarial activities of the chloroquine-based andalpha;,andbeta;-unsaturated amide derivative compounds having the novel structure, has been conducted by testing cytotoxicity in the growth of Hela cells and also by measuring inhibitory activities on the growth of P. falciparum strain. Accordingly, the novel compounds have shown excellence in antimalarial activities. Thus, the composition can be useful for pharmaceutical compositions for preventing and treating malaria.COPYRIGHT KIPO 2016
Synthetic approach to wortmannilactone C
Brandt, Damien,Dittoo, Aurlia,Bellosta, Vronique,Cossy, Janine
supporting information, p. 816 - 819 (2015/03/18)
A diastereomer of wortmannilactone C has been synthesized according to a convergent and versatile strategy from tert-butyl 3-hydroxypropanoate and ethyl (R)-3-hydroxybutanoate. The key steps are a Liebeskind cross-coupling and a Horner-Wadsworth-Emmons (HWE) reaction to construct the macrolactone. The stereogenic centers at C9, C11, and C21 were controlled by enantioselective allyltitanations, and the C19 stereocenter was controlled by using a Noyori reduction of an acetylenic ketone.
Synthesis of orthogonally protected (2S)-2-amino-adipic acid (α-AAA) and (2S,4 R)-2-amino-4-hydroxyadipic acid (Ahad)
Yadav, Saroj,Taylor, Carol M.
, p. 5401 - 5409 (2013/07/26)
(2S,4R)-2-Amino-4-hydroxyadipic acid (Ahad) building block 45 was synthesized in 11 steps and 6.5% overall yield from commercially available materials. Key steps in stereocontrol were an asymmetric conjugate addition employing a proline-based catalyst and a syn-selective intramolecular-conjugate addition of an oxygen nucleophile to an α,β-unsaturated ester. To enable incorporation of α-amino-adipic acid (α-AAA) and Ahad into peptides, a truly orthogonal protecting group scheme was developed, encompassing an allyloxycarbonyl (Alloc) carbamate for Nα, a tert-butyl ester for the δ-COOH, an acetol ester for the α-COOH, and a tert- butyldimethylsilyl ether for the γ-hydroxy group of Ahad.
The Wittig-Horner reaction for the synthesis of neratinib
Gu, Ning,Yang, Jiabin,Wang, Peng,Li, Lushen,Chen, Yang,Ji, Min
, p. 3105 - 3110 (2013/09/23)
The Wittig-Horner reaction is a classic method to get alkenes by reaction phosphonates with carbonyl compounds. In this study, it was used for the synthesis of the anticancer drug neratinib. In this method, ethyl diethoxyphosphinylacetate and dimethylaminoacetaldehyde diethylacetal, replacing (E)-4-(dimethylamino)but-2-enoyl acid hydrochloride and oxalyl chloride, were used to synthesize the 6-position side chain of neratinib.
Stereoselective control in the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents: Experimental investigation and theoretical rationalization
Qi, Hengzhen,Li, Xinyao,Xu, Jiaxi
supporting information; experimental part, p. 2702 - 2714 (2011/05/19)
The stereoselectivity of the Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents was investigated experimentally by determination of the product stereochemistry and theoretically via DFT calculations. The results indicate that imines preferentially attack the less sterically hindered exo-side of the ketenes to generate zwitterionic intermediates. Subsequently, for cyclic imines, the intermediates undergo a conrotatory ring closure directly to produce β-lactams, while for linear imines, the imine moiety of the intermediates isomerizes to more stable intermediates, which further undergo a conrotatory ring closure to afford trans-β-lactams. The steric hindrance and the isomerization, rather than the torquoelectronic effect, play crucial roles in controlling the stereoselectivity in the practical Staudinger reactions involving monosubstituted ketenes with electron acceptor substituents, although the unaccessible borylketene with a powerful electron acceptor group controls the stereoselectivity torquoelectronically, in theory.
Z-selective intramolecular horner-wadsworthemmons reaction for the synthesis of macrocyclic lactones
Ando, Kaori,Narumiya, Kenji,Takada, Hirokazu,Teruya, Taiji
scheme or table, p. 1460 - 1463 (2010/06/15)
(Figure Presented) When the substrates (ArO)2P(O)CH 2CO2...CHO (Ar = Ph, o-tBuPh) were added to a THF solution containing 3 equiv of NaH at 0 °C or Nal DBU at rt over 1-10 h, the intramolecular Horner-Wadsworth-Emmons reaction proceeded efficiently to give the 12-18-membered-ring lactones in 69-93% yields with 89-100% Z selectivity. On the other hand, (EtO)2P(O)CH2CO2-GHO gave the 13-18-membered-ring lactones in 52-82% yields with 89-99% E selectivity using LiCI-DBU in MeCN or THF.
Synthesis and antibacterial activity of new aryl / alkyl phosphonates via Michaelis-Arbuzov rearrangement
Syam Prasad, Gandavaram,Manjunath, Manubolu,Kishore Kumar Reddy, Kachi Reddy,Sarathi Reddy, Obulam Vijaya,Suresh Reddy, Cirandur
, p. 128 - 135 (2015/01/08)
Synthesis of new aryl / alkyl phosphonates 3a-j has been accomplished via a Michaelis- Arbuzov-type rearrangement by the reaction of aryl / alkyl halide (1a-j) with triethyl phosphite (2) in dry toluene at reflux temperature. Products 3a-j were characterized by IR, 13C and 31P NMR and their antibacterial activity was evaluated.
Synthesis of α-fluorinated phosphonoacetate derivatives using electrophilic fluorine reagents: Perchloryl fluoride versus 1-chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor)
Marma, Mong S.,Khawli, Leslie A.,Harutunian, Vahak,Kashemirov, Boris A.,McKenna, Charles E.
, p. 1467 - 1475 (2007/10/03)
Triethyl fluorophosphonoacetate and triethyl difluorophosphonoacetate are directly synthesized from triethyl phosphonoacetate by treatment with NaH and 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor). Contrary to a recent report [C.J. Hamilton, S.M. Roberts, J. Chem. Soc., Perkin Trans. 1 (1999) 1051-1056], the reaction proceeded in THF without the need for DMF as a co-solvent. This method is more selective and provides greater convenience and safety than fluorination of the same substrate by treatment with t-BuOK and perchloryl fluoride (FClO3) in toluene while offering advantages over a number of previously described methods employing alternative electrophilic fluorinating reagents or other approaches. Either the monofluoro or the difluoro product can be obtained predominantly by adjusting the molar ratio of base and Selectfluor. Triethyl 2-fluoro-2-phosphonopropionate (ethyl 2-(diethoxyphosphinyl)-2-fluoropropanoate) is also more conveniently made from triethyl 2-phosphonopropanoate using NaH/Selectfluor in THF than with FClO3/t-BuOK in toluene. Detailed procedures are given for obtaining the corresponding triacids in quantitative yield from the fluorinated triesters by P,P-silyldealkylation with bromotrimethylsilane followed by one-pot double hydrolysis with H2O, and isolation as stable dicyclohexylammonium (DCHA) or pyridinium (Py) salts. Substitution of EtOH for H2O in the latter procedure provides the CO-ester phosphonic diacids, isolated as DCHA salts, in one step. 1H, 13C, 31P and 19F NMR data are given for the compounds prepared.
