- Design, synthesis and biological evaluation of novel diazaspiro[4.5]decan-1-one derivatives as potential chitin synthase inhibitors and antifungal agents
-
A series of 2,8-diazaspiro[4.5]decan-1-one derivatives were designed, synthesized and screened for their inhibition activities against chitin synthase (CHS) and antimicrobial activities in vitro. The biological assays revealed that compounds 4a, 4e, 4h, 4j, 4o, 4q and 4r exhibited moderated to excellent potency against CHS with IC50 values ranging from 0.12 to 0.29 mM. Compounds 4e, 4j with IC50 value of 0.13 mM, 0.12 mM respectively, showed excellent inhibition potency among these compounds, which were similar to that of polyoxin B whose IC50 value was 0.08 mM. Meanwhile, the screening of the antifungal activity showed that compounds 4j and 4r had the same potency of inhibiting the growth of A. fumigatus with MIC value of 0.08 mmol/L. Compound 4d displayed excellent activity against C. albicans (ATCC 90023) with MIC value of 0.04 mmol/L, which was superior to fluconazole (0.104 mmol/L) and polyoxin B (0.129 mmol/L). The result of antibacterial assay showed that these compounds had little potency against those selected bacteria strains including three Gram-positive bacteria and three Gram-negative bacteria. Furthermore, the combination use of 4c-fluconazole, 4i-fluconazole, 4j-fluconazole, and 4o-fluconazole against C. albicans,A. fumigatus and A. flavus showed additive or synergistic effects. These results indicated that the designed compounds serve as potential chitin synthase inhibitors and have selectively antifungal activities.
- Li, Bing,Wang, Kaiyuan,Zhang, Rui,Li, Baihui,Shen, Yangli,Ji, Qinggang
-
supporting information
(2019/09/07)
-
- Enantioselective vinylation of aldehydes with the vinyl Grignard reagent catalyzed by magnesium complex of chiral BINOLs
-
Enantioselective vinylation of aldehydes via direct catalytic asymmetric Grignard reaction of aldehdyes and the vinyl Grinard reagent is a long-standing challenge. This work demonstrated that the magnesium (S)-3,3′-dimethyl BINOLate enantioselectively catalyze the direct vinylation of aldehydes with the deactivated vinylmagnesium bromide by bis(2-[N,N′-dimethylamino]ethyl) ether (BDMAEE) in the addition of n-butylmagnesium chloride. The highest ee of 63% was achieved up to date.
- Wang, Pei,Ma, Guo-Rong,Yu, Sheng-Li,Da, Chao-Shan
-
supporting information
p. 79 - 86
(2018/12/13)
-
- High-purity manufacturing method of dialkyl tartrate
-
The invention provides an efficient method for manufacturing high purity tartaric acid dialkyl esters, including the steps of: reacting fatty alcohol of alkyl with 1-4 carbon atom(s) with tartaric acid without solvents and acid catalysts, and then performing concentration until moisture content becomes below 1.0 weight% to obtain a first esterification reaction liquid; adding fatty alcohol of a same kind into the first esterification reaction liquid to prepare a homogeneous solution, and then adding thionyl chloride for reaction to perform concentration to obtain a second esterification reaction liquid; adding solid shaped bicarbonate into the second esterification reaction liquid for neutralization, and performing solid-liquid separation, concentration and thin-film distillation. According to the method, high purity tartaric acid dialkyl esters with the content of sulfurous acid dialkyl esters below 0.1% and content of tartaric acid monoalkyl esters below 0.1% is obtained.
- -
-
Paragraph 0165-0170
(2017/03/24)
-
- A highly efficient, enantioselective and recyclable mesoporous silica-based Mn(ii) catalyst for asymmetric oxidation of thioanisole
-
The development of environmentally benign reactions is an important goal in synthetic organic chemistry and chemical engineering. However, catalytic enantioselective oxidations using transition-metal complexes are limited when the oxidant is hydrogen peroxide. A hydrazone based asymmetric ligand (H2L) was used to prepare a heterogeneous catalyst by the immobilization of its manganese complex, [{Mn(H2O)2Cl2}2(H2Btar)] (1), on mesoporous support SBA-15 via the post grafting method (H2L = 2,3-O-4-hydroxybenzhydrazidebenzylidene-d-tartrate). The heterogeneous asymmetric catalyst 1-SBA15 was characterized by elemental analysis; small angle X-ray diffraction (SAX), scanning electron microscopy (SEM), nitrogen sorption measurement, Fourier transform infrared spectroscopy and EPR spectroscopy. The asymmetric oxidation of thioanisole (PhSMe) was achieved with hydrogen peroxide in the presence of 1-SBA15 in excellent conversion and enantioselectivity (>99% ee). Compared to a homogeneous catalyst, the heterogenized catalyst is more stable and can be recycled four times without any significant loss of activity. Immobilization of complex 1 onto SBA-15 increased the selectivity toward sulfone in the oxidation.
- Alavi, Sohaila,Hosseini-Monfared, Hassan,Aleshkevych, Pavlo
-
p. 48827 - 48835
(2015/01/08)
-
- Practical synthesis of trans-dihydroxybutyrolactols as chiral C4 building blocks and their application to the synthesis of polyhydroxylated alkaloids
-
Practical syntheses of trans-dihydroxybutyrolactols 2a, 2b and 2c from inexpensive chiral pool compounds l-ascorbic, d- and l-tartaric acid have been achieved on a multigram-scale. The synthetic applications of these chiral building blocks have been demonstrated in the efficient total or formal synthesis of polyhydroxylated alkaloids (+)-lentiginosine and (-)-deacetylanisomycin in concise routes. The Royal Society of Chemistry 2013.
- Zeng, Jing,Zhang, Qian,Zhang, Hong-Kui,Chen, Anqi
-
p. 20298 - 20307
(2013/11/06)
-
- A study on the racemization step in the synthesis of pyrrolidinols via cyclic α-hydroxyimides
-
Analytical HPLC methods for the determination of the enantiomeric excess of N-protected malimides 1 as well as the corresponding pyrrolidinol 5 and tartarimides 2 and 3 have been established. On this basis, a study to reveal the racemization step in the synthesis of pyrrolidinols from α-hydroxyacids, via chiral cyclic α-hydroxyimides, has been undertaken. It was confirmed that the known, one-step method for the synthesis of the N-protected chiral cyclic imides from α-hydroxydiacids proceeded with little racemization, and partial racemization has been proven to occur during the reduction of the resultant imide 1a with LAH to yield the corresponding pyrrolidinol 5. Conditions have been defined in order to avoid racemization in the LAH reduction step.
- Zheng, Jin-Li,Liu, Hui,Zhang, Yu-Feng,Zhao, Wei,Tong, Jin-Shuan,Ruan, Yuan-Ping,Huang, Pei-Qiang
-
scheme or table
p. 257 - 263
(2011/05/12)
-
- ORGANIC-INORGANIC HYBRID CHIRAL SORBENT AND PROCESS FOR THE PREPARATION THEREOF
-
The present invention provides an organic-inorganic hybrid chiral sorbent for chiral resolution of various racemic compounds viz. racemic mandelic acid, 2-phenyl propionic acid, diethyl tartrate, 2,2′-dihydroxy-1,1′-binaphthalene (BINOL) and cyano chromene oxide with excellent chiral separation (enantiomeric excess, 99%) in case of mandelic acid under medium pressure column chromatography. These optically pure enantiomers find applications as intermediates in pharmaceutical industries.
- -
-
Page/Page column 11-12
(2010/12/29)
-
- Studies toward the total synthesis of cyclodidemniserinol trisulfate. Part II: 3,5,7-Trisubstituted 6,8-dioxabicyclo [3.2.1] octane core structure construction via I2-mediated deprotection and ring closure tandem reaction
-
The 3,5,7-trisubstituted 6,8-dioxabicyclo [3.2.1] octane core structure was synthesized by employing a chiral pool convergent synthesis strategy and the I2-mediated simultaneous deprotection and ring closure reaction as the key step, providing a practical and efficient synthetic approach applicable to the further total synthesis of the natural product cyclodidemniserinol trisulfate.
- Liu, Jian-Hua,Long, Ya-Qiu
-
supporting information; experimental part
p. 4592 - 4594
(2009/10/18)
-
- A versatile approach to pyrrolidine azasugars and homoazasugars based on a highly diastereoselective reductive benzyloxymethylation of protected tartarimide
-
A highly diastereoselective synthesis of enantio-enriched all trans-3,4-dibenzyloxyl-5-benzyloxymethyl-2-pyrrolidinone 13a was developed based on SmI2-mediated benzyloxymethylation of O,O′-dibenzyltartarimide. The versatility of 13a and its antipode as the key building blocks for the asymmetric synthesis of pyrrolidine azasugars and homoazasugars has been demonstrated by elaborating them into naturally occurring DAB 1 (1), LAB 1 (2), N-hydroxyethyl-DAB 1 (4), 6-deoxy-DMDP 7, and 5-epi-radicamine B 36 as well as the reductive ring-opening product 35.
- Zhou, Xiang,Liu, Wen-Jun,Ye, Jian-Liang,Huang, Pei-Qiang
-
p. 6346 - 6357
(2008/02/05)
-
- Boric acid catalyzed chemoselective esterification of α- hydroxycarboxylic acids
-
Boric acid catalyzes the selective esterification of α- hydroxycarboxylic acids without causing significant esterification to occur with other carboxylic acids. The procedure is simple, high-yielding, and applicable to the esterification of α-hydroxy carboxylates in the presence of other carboxylic acids including β-hydroxyacids within the same molecule.
- Houston, Todd A.,Wilkinson, Brendan L.,Blanchfield, Joanne T.
-
p. 679 - 681
(2007/10/03)
-
- An improved synthesis of aziridine-2,3-dicarboxylates via azido alcohols - Epimerization studies
-
The reasons for epimerization of 3-azido-2-hydroxysuccinates observed during the ring opening of epoxides or cyclic sulfites with sodium azide is now clarified. It is caused by the high acidity of the proton at the 3-position. This is proven by a proton deuterium exchange in assays with either D 2O or DCl containing solvents. The anti-3-azido-2-hydroxysuccinates serve as intermediates for enantiomerically pure trans-aziridine-2,3- dicarboxylates for which an optimized synthetic pathway is presented. The first example of an enantiomerically pure mixed diester of the aziridine-2,3- dicarboxylic acid the synthesis of the allyl ethyl ester is reported herein.
- Breuning, Alexander,Vicik, Radim,Schirmeister, Tanja
-
p. 3301 - 3312
(2007/10/03)
-
- Synthesis of novel C2-symmetric and enantiomerically pure bisbenzoxazoles and bisbenzothiazoles derived from L- and D-tartaric acids
-
Five pairs of novel C2-symmetric and enantiomerically pure bisbenzoxazoles and a pair of bisbenzothiazoles derived from L- and D-tartaric acids have been synthesized from L- and D-2,3-O-isopropylidenetartaric dichlorides and o-aminophenol derivatives or o-aminothiophenol, respectively, in two- or one-step reactions. The mechanism for the formation of bisbenzoxazoles and bisbenzothiazoles was suggested. The UV and 1H NMR spectra showed that no coordination between the bisbenzoheterazoles and Cu(I) or Ni(II) cations occurred due to the lack of a sufficiently basic nitrogen donor atom in the benzoheterazole moiety.
- Jiao, Peng,Xu, Jiaxi,Zhang, Qihan,Choi, Michael C.K.,Chan, Albert S.C.
-
p. 3081 - 3088
(2007/10/03)
-
- Indium-mediated chemoselective deprotection of trichloroethoxycarbonyl and trichloroacetyl groups
-
A new, mild, and chemoselective method for the deprotection of trichloroethoxylcarbonyl and trichloroacetyl groups is described.
- Valluri, Muralikrishna,Mineno, Tomoko,Hindupur, Rama M.,Avery, Mitchell A.
-
p. 7153 - 7154
(2007/10/03)
-
- Applications of Biotransformations in Organic Synthesis: Preparation of Enantiomerically Pure Esters of cis- and trans-Epoxysuccinic Acid
-
Chemical and enzymatic procedures have been investigated for the resolution of esters of trans-epoxysuccinic acid (trans-oxirane-2,3-dicarboxylic acid).A successful resolution was achieved by transesterification of the diethyl ester against heptanol catalysed by the lipase from Rhizopus javanicus.Asymmetrization of cis-epoxysuccinic acid was achieved by enantioselective and regiospecific hydrolysis of the racemic diethyl ester of 2-(toluene-p-sulfonyloxy)tartaric acid , followed by esterification with 2-methylpropanol and oxirane formation.
- Crout, David H. G.,Gaudet, S. B.,Hallinan, Keith O.
-
p. 805 - 812
(2007/10/02)
-
- STEREOSPECIFIC SYNTHESIS OF ISOMERIC 4-SUBSTITUTED 9-(2,3-DIHYDROXYBUTYL)ADENINES
-
Reduction of ethyl 2,3-O-isopropylidene-D-tartrate with sodium borohydride afforded (4S,5S)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (Va) which was benzoylated to give monobenzoyl derivative Vd and further transformed into p-toluenesulfonyl derivative Ve.Reaction of the compound Ve with sodium salt of adenine followed by methanolysis gave 2,3-O-isopropylidene derivative Vf which on acid hydrolysis afforded 9-(2S,3S)-(2,3,4-trihydroxybutyl)adenine (Ia).The enantiomer IIa was obtained from 3,4-O-isopropylidene-D-mannitol via (4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-dimethanol (VIa) using the same procedure.Reaction of compounds Vf and VIf with p-toluenesulfonyl chloride afforded 4-O-p-toluenesulfonyl derivatives Vg and VIg.These compounds were also obtained from Va and VIa via di-p-toluenesulfonyl derivatives Vc and VIc by reaction with sodium salt of adenine.Treatment of compounds Vg and VIg with sodium iodide gave 4-iodo derivatives Vh and VIh which on reaction with tri-n-butyltin hydride, followed by acid hydrolysis, afforded enantiomeric threo-2,3-dihydroxybutyl derivatives Ib and IIb.Compounds Vg and VIg on treatment with sodium azide, subsequent catalytic hydrogenation of the intermediates Vj and VIj and acid hydrolysis afforded enantiomeric threo-9-(4-amino-2,3-dihydroxybutyl)adenines (Ic, IIc).Reaction of methyl threo-3-phenylglycerate (VIIb) with acetone, followed by reduction with lithium aluminum hydride, gave 2,2-dimethyl-4-phenyl-1,3-dioxolane-5-methanol (VIIIb) which was converted by reaction with p-toluenesulfonyl chloride, condensation with sodium salt of adenine and acid hydrolysis into 9-(RS)-threo-(3-phenyl-2,3-dihydroxypropyl)adenine (I, IId).Methyl ester of D-eritadenine (IXb) was transformed into 2,3-O-isopropylidene derivative XIa which on reduction with sodium borohydride afforded the alcohol XIb.Its acid hydrolysis gave 9-(2R,3S)-erythro-(2,3,4-trihydroxybutyl)adenine (IIIa); tosylation of compound XIb, successive treatment with sodium iodide and tri-n-butyltin hydride and acid hydrolysis afforded 9-(2R,3S)-erythro-(2,3-dihydroxybutyl)adenine (IIIb).The enantiomers IVa and IVb were obtained analogously from L-eritadenine.The racemic derivative Ib + IIb was prepared from (RS)-threo-2,3-dihydroxybutyric acid via p-toluenesulfonyl derivative of racemic 2,2,4-trimethyl-1,3-dioxolane-5-methanol (IIIc) by reaction of sodium salt of adenine followed by acid hydrolysis.
- HOLY, Antonin
-
p. 173 - 189
(2007/10/02)
-
