- A convenient resolution method for 1,1′-bi-2-naphthol and 4,4′-dibromo-1,1′-spirobiindane-7,7′-diol with menthyl chloroformate in the presence of TBAB
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A convenient resolution method for 1,1′-bi-2-naphthol and 4,4′-dibromo-1,1′-spirobiindane-7,7′-diol has been developed with crude (-)-menthyl chloroformate as the resolution reagent in the presence of tetrabutylammonium bromide acting as a phase transfer catalyst in an aqueous NaOH/CH2Cl2 two phase solution. The deprotection of the hydroxy group was carried out via an aqueous KOH/EtOH solution. Both enantiomers of 1,1′-bi-2-naphthol and 4,4′-dibromo-1,1′- spirobiindane-7,7′-diol were obtained in high yields. Both ee's of (S)-(+) and (R)-(-)-4,4′-dibromo-1,1′-spirobiindane-7,7′-diol were above 99%. Most of the (-)-menthol could be easily recovered in a deprotection procedure and thus be reused for the formation of (-)-menthyl chloroformate without further purification.
- Li, Zhian,Liang, Xinmiao,Wu, Fan,Wan, Boshun
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Read Online
- An efficient and practical synthesis of BINAM derivatives by diastereoselective [3,3]-rearrangement
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This work describes an efficient, practical, and diastereoselective synthesis of enantiomerically pure BINAM derivatives by utilizing the acid-catalyzed [3,3]-sigmatropic rearrangement of readily accessible N-(-)-menthoxycarbonyl-diaryl hydrazines as a key step. The yield of the rearrangement is very high and two diastereomers thus obtained are easily separable.
- Li, Bing,Zhang, Shengyong,Chen, Weiping
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Read Online
- Synthesis method of acetaldehyde alcohol optical active ester
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The invention provides a synthesis method of an acetaldehyde alcohol optical active ester, which comprises the following steps of: reacting L-menthol as a raw material with triphosgene to obtain L-menthyl chloroformate, reacting the L-menthyl chloroformate with 1, 4-cis-butenediol, recrystallizing, and carrying out oxidation reaction under an ozone condition to obtain the acetaldehyde alcohol optical active ester. In the whole synthesis process, the initial raw materials are low in price and easy to obtain, the synthesis process is simple, the synthesis conditions are mild, and the synthesis cost of the acetaldehyde alcohol optical active ester is greatly reduced. The raw materials are good in reaction selectivity and high in atom utilization rate, and the obtained acetaldehyde alcohol optical active ester has high yield and purity. Meanwhile, few three-waste pollutants are generated in the synthesis process, and the method is suitable for industrial large-scale production of the acetaldehyde alcohol optical active ester, so that large-scale synthesis of drugs such as emtricitabine and lamivudine is facilitated.
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Paragraph 0024-0026
(2021/05/08)
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- Spiro Scaffold Chiral Organocatalyst of 3,2′-Pyrrolidinyl Spiro-oxindole Amine and Its Catalytic Evaluation in the Enantioselective Aldol Condensation between 3-(3-Hydroxy-1 H-pyrazol-1-yl)-Oxindole and Paraformaldehyde
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The spiro scaffold chiral organocatalyst of 3,2′-pyrrolidinyl spiro-oxindole amine was successfully prepared from racemic spiro-oxindole amine using l-menthol as a chiral pool in 4 steps in 28%-40% overall yields with at least 99% ee in scale-up preparation, and its catalytic activity was evaluated in the enantioselective aldol condensation between 3-(3-hydroxy-1H-pyrazol-1-yl)-oxindole and paraformaldehyde. The spiro organocatalyst showed superior catalytic activity and selectivity compared with its counterparts, and most substrates offered good to excellent results with up to 96% yield in 96% ee.
- Zou, Ying,Huang, Zhi-Cheng,Xiang, Min,Li, Chen-Yi,Li, Xia,Tian, Fang,Wang, Li-Xin
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p. 17371 - 17379
(2021/12/02)
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- PROCESS FOR PRODUCING CHLOROFORMATE COMPOUND
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The present invention provides a method for safely producing a large amount of chloroformate compound with high yield. The chloroformate compound can be produced by mixing and reacting a solution of triphosgene, an amine and an alcohol compound in a flow reactor. The chloroformate compound can also be produced by mixing and reacting a solution of triphosgene with a solution comprising an amine and an alcohol compound in a flow reactor. The amine is preferably tributylamine, and preferably used in an amount of 0.8 to 3 equivalents relative to an amount of the alcohol compound.
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Paragraph 0068; 0069; 0078
(2019/06/20)
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- A preparation method of lamivudine
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The invention discloses a method for preparation of lamivudine. Refined pure 5 S - (cytosine base - 1 ') - 1, 3 - oxathiolane - 2 - ethoxy carbonyl - (1' R, 2'S, 3' R) - menthyl ester; in the weak base and the solvent removed under the condition of chiral L - menthol to get a product of lamivudine. The material of the invention is cheap, the reagents used in the environmental protection, steps is relatively short, mild reaction conditions, atom utilization rate high, high yield, high chemical purity of the obtained product, reach the medical standard, suitable for large-scale production of lamivudine preparation method.
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Paragraph 0042; 0046-0048
(2019/04/02)
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- A Suitqable to preparation method
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The invention discloses a Suitqable to preparation method. Refined pure 5 S - (5 '- fluorocytosine yl - 1') - 1, 3 - oxathiolane - 2 - ethoxy carbonyl - (1 'R, 2'S, 3' R) - menthyl ester; in the weak base and the solvent removed under the condition of chiral L - menthol get products Suitqable to. The invention required the starting raw material is cheap, mild reaction conditions, the atom utilization rate is high, the operation technique is simple, the reagents used in the environmental protection, the resulting high purity, reach the medical standard, is suitable for the industrial production of kindness or gemcitabine.
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Paragraph 0042; 0046-0048
(2019/04/02)
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- Safe and Efficient Phosgenation Reactions in a Continuous Flow Reactor
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Phosgene is widely used in organic synthesis owing to its high reactivity, utility, and cost efficiency. However, the use of phosgene in batch processes on the industrial scale is challenging owing to its toxicity. An effective method to minimize reaction volumes and mitigate the safety risks associated with hazardous chemicals is the use of flow reactors. Consequently, we have established a flow reaction system using triphosgene and tributylamine, which affords a homogeneous reaction that avoids clogging issues. In addition, we have demonstrated that this methodology can be applied to a wide variety of phosgene reactions, including the preparation of pharmaceutical intermediates, in good to excellent yields.
- Yasukouchi, Hiroaki,Nishiyama, Akira,Mitsuda, Masaru
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supporting information
p. 247 - 251
(2018/02/23)
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- Levorotatory meptazinol prodrug as well as preparation method and purpose thereof
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The invention provides a levorotatory meptazinol prodrug as well as a preparation method and a purpose thereof, wherein the levorotatory meptazinol prodrug is a compound as shown in a formula I or a stereoisomer, a geometrical isomer, a tautomer, oxynitride, a hydrate, a solvate, a metabolite or a pharmaceutically acceptable salt of the compound as shown in the formula I. The compound is low in hepatic first pass effect and high in bioavailability; a medicine which uses the compound as an active component can be used for treating a neurodegenerative disease or various kinds of acute and chronic pain, such as a wound, postoperative, obstetrical and cancer pain, hemicrania, neuropathic pain and the like.
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Paragraph 0119; 0121; 0122
(2017/07/19)
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- Variochelins, Lipopeptide Siderophores from Variovorax boronicumulans Discovered by Genome Mining
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Photoreactive siderophores have a major impact on the growth of planktonic organisms. To date, these molecules have mainly been reported from marine bacteria, although evidence is now accumulating that some terrestrial bacteria also harbor the biosynthetic potential for their production. In this paper, we describe the genomics-driven discovery and characterization of variochelins, lipopeptide siderophores from the bacterium Variovorax boronicumulans, which thrives in soil and freshwater habitats. Variochelins are different from most other lipopeptide siderophores in that their biosynthesis involves a polyketide synthase. We demonstrate that the ferric iron complex of variochelin A possesses photoreactive properties and present the MS-derived structures of two degradation products that emerge upon light exposure.
- Kurth, Colette,Schieferdecker, Sebastian,Athanasopoulou, Kalliopi,Seccareccia, Ivana,Nett, Markus
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p. 865 - 872
(2016/05/24)
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- Synthesis, characterization, antibacterial and antifungal evaluation of novel monosaccharide esters
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A novel series of 3-(2-furyl)acrylate monosaccharide esters Ia-f and menthyloxycarbonyl monosaccharide esters IIa-f were designed and synthesized. The chemical structures of the target compounds were confirmed by IR, 1H- and 13C-NMR and ESI-MS, and the target compounds were investigated for their in vitro antibacterial and antifungal activities. The antibacterial screening results showed that the 3-(2-furyl)acrylate monosaccharide ester derivatives Ia-f were either inactive or only weakly active against the three Gram-positive bacterial strains tested, whereas the menthyloxycarbonyl monosaccharide ester derivatives IIa-f exhibited higher levels of activity, with compound IIe being especially potent. The results of the antifungal screening revealed that compounds Ib, Ie, IIb and IIc displayed potent in vitro activities, whereas If and IIf showed promising activities against all of the microorganisms tested, with If exhibiting levels of activity deserving of further investigation.
- Shen, Yi,Sun, Yufeng,Sang, Zhipei,Sun, Chengjun,Dai, Ya,Deng, Yong
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experimental part
p. 8661 - 8673
(2012/10/08)
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- PROCESS FOR STEREOSELECTIVE SYNTHESIS OF LAMIVUDINE
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A process for stereoselective synthesis of lamivudine, comprising (a) glycosylation of compounds of formula (I) and cytosine or protected cytosine, separating the resulting products by crystallization to afford intermediates of formula (II); (b) removing
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Page/Page column 4-5
(2010/04/23)
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- A PROCESS FOR STEREOSELECTIVE SYNTHESIS OF LAMIVUDINE
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The present invention discloses a process for stereoselective synthesis of Lamivudine comprising the following steps: (a) performing a glycosylation reaction between the compound of formula (I) and cytosine or protected cytosine, and separating the reaction product by recrystallization to obtain the intermediate of formula (II); and (b) deprotecting the intermediate of formula (II) to obtain Lamivudine.
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Page/Page column 7
(2010/04/24)
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- Design and synthesis of chiral N-chloroimidodicarbonates: Application to asymmetric chlorination of silyl enol ethers
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(Chemical Equation Presented) New chiral N-chloroimidodicarbonates, which function as efficient chiral chlorinating agents, were designed and synthesized. Among these, C2-symmetric (1R,2S,5R)-(-)-menthyl-N- chloroimidodicarbonate 2a provided moderate to good enantioselectivity (up to 40%) for the chlorination of silyl enol ethers to afford α-chloroketones only in the presence of a suitable Lewis acid such as Sm(OTf)3.
- Hajra, Saumen,Bhowmick, Manishabrata,Maji, Biswajit,Sinha, Debarshi
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p. 4872 - 4876
(2008/02/05)
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- Method for the preparation of aliphatic chloroformates
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A method for preparing an aliphatic chloroformate comprising, introducing a mixture of at least one aliphatic hydroxyl compound, phosgene, at least one solvent, and optionally at least one organic base into a flow reactor to obtain a unidirectional flowing reaction mixture. The at least one aliphatic hydroxyl compound comprises at least one aliphatic hydroxyl group. The unidirectional flowing reaction mixture is maintained at a temperature between about 0° C. and about 60° C. to produce a single product stream comprising an aliphatic chloroformate.
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Page/Page column 7-8
(2008/06/13)
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- New acylnitroso compounds for the asymmetric oxyamination of dienes
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A series of new enantiomerically pure acylnitroso compounds have been prepared and tested as dienophiles for the asymmetric oxyamination of dienes. Very high selectivities were obtained with acylnitroso compounds derived from diphenylmethoxymethyl pyrrolidine 2c, the C2-symmetric pyrrolidines 2d-e and camphorsultam 2f.
- Gouverneur,McCarthy,Mineur,Belotti,Dive,Ghosez
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p. 10537 - 10554
(2007/10/03)
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- Synthesis of conduramines from N-tert-butoxycarbonylpyrrole
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Two related synthetic strategies were devised to convert the Diels- Alder adduct 3c of Boc-pyrrole and p-toluenesulfonylacetylene into various racemic and optically pure conduramines. One process consists of the regio- and stereoselective hydroxylation of 3c to the tri- and dihydroxylated azabicyclo-[2.2.1]heptane derivatives 10b (Scheme 2) and the exo-endo mixture 13-14 (Scheme 3). Anionic fragmentation of 10b (methylmagnesium bromide) and of the 13-14 sulfone mixture (lithium bis-(trimethylsilyl)amide) generated the corresponding tri- and dihyroxylated aminocyclohexenes 17 and 16 (Scheme 3). Compound 17 is an aminocyclitol with a stereochemistry and partial aminotriol sequence identical to that found in neoinosamine. Compound 16 served as a source of the protected and free aminodiols 35b and 35a (Scheme 6), which were stereospecifically epoxidized to 36 (Scheme 6) and 40 (Scheme 7). Phenylselenide cleavage of these epoxides provided 37 (Scheme 6) and 41a (Scheme 7), which after selenoxide cycloelimination and protecting group manipulation were converted into (±)-conduramine C-1 (39a, Scheme 6) and the previously unreported, all-cis-conduramine D-1 (43a, Scheme 7). In a second process, anionic fragmentation of the bicyclic system is effected prior to introduction of the hydroxyl groups, as exemplified by the high-yielding conversion of the exo-endo mixture of azabicycloheptenes 11 and 12 into the aminocyclohexadiene 15 (Scheme 3). Osmate catalyzed cis-dihydroxylation of the derived bis-Boc derivative 20 (Scheme 4) led stereospecifically to the α-cis-diol 21 which was transformed into (±)-conduramine A-1 (27a) and its tetraacetyl derivative 27b via the epoxy compound 24. On the other hand, peracid oxidation of the diene 15 gave the β-epoxide 28 (Scheme 5) which was cleaved to the trans-diol 29 with aqueous sulfuric acid. This diol was converted into (±)-conduramine F-1 (34a) and its tetraacetyl derivative (34b) by a reaction sequence similar to that used for the other conduramine syntheses. Fractional crystallization of the diastereomeric mixture of Michael adducts obtained from (±)-3c and (-)-methyl lactate gave (-)-44a and (-)-45a both in ≤47% yield (Scheme 8). Both the carboxylic acid (+)-44b and the primary alcohol (+)-46 derived from (-)-44a were converted into (-)-3c with excess methylmagnesium bromide (ca. 40% overall yield). In the same way (-)-45a was transformed into optically pure (+)-3c. (-)-3c and (+)-3c were then converted into (-)-conduramine C-1 [(-)-39a] and (+)-conduramine D-1 [(+)-43a] by procedures identical to those used for the racemic compounds.
- Leung-Toung, Regis,Liu, Yanzhou,Muchowski, Joseph M.,Wu, Yu-Lin
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p. 3235 - 3250
(2007/10/03)
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- Total synthesis of (-)-epibatidine using an asymmetric Diels-Alder reaction with a chiral n-acylnitroso dienophile
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An asymmetric total synthesis of (-)-epibatidine (1), isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor, of the family Dendrobatidae, has been achieved by virtue of the development of asymmetric hereto Diels-Alder (D-A) cycloaddition with an N-acylnitroso dienophile bearing the optically active 8-arylmenthol as a chiral source. Thus, in situ oxidation of the hydroxamic acid ent-12f incorporating the (1S,2R,5S)-8-(2- naphthyl)menthyl auxiliary was performed using the Swern conditions to produce the acylnitroso dienophile, which reacted at once with 2-chloro-5- (1,5-cyclohexadienyl)pyridine (7) to provide the (1S,4R)-meta-aza cycloadduct 24 as a major diastereoisomer. The observed facial diastereoselectivity is consistent with a transition-state model with the naphthyl group in 'stacked' position and with the acylnitroso group in the s-cis conformation, wherein π attractive interaction between the naphthyl and nitrosocarbonyl groups may contribute to facial control. Compound 24 underwent hydrogenation followed by removal of the chiral auxiliary with LiH2NBH3 and reductive cleavage of the N-O bond with Mo(CO)6 to give the amino alcohol derivative 29, which was converted to (-)-epibatidine via bromination followed by cyclization.
- Aoyagi, Sakae,Tanaka, Ryuta,Naruse, Masaichi,Kibayashi, Chihiro
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p. 8397 - 8406
(2007/10/03)
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- Lewis acid-promoted asymmetric conjugate allylation of N-acyl-2,3-dihydro-4-pyridones induced by intramolecular π interactions
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Lewis acid-promoted conjugate addition reaction of an allylsilane to a series of the chiral 8-arylmenthol-derived N-acyl-2,3-dihydro-4-pyridones leads to the 2-allyl-4-piperidones with moderate to high levels of asymmetric induction, indicating π-stacking contribution to chirality control. This methodology was applied to the asymmetric synthesis of (-)-N-methylconiine. Copyright (C) 1996 Elsevier Science Ltd.
- Sato, Masayuki,Aoyagi, Sakae,Yago, Seiji,Kibayashi, Chihiro
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p. 9063 - 9066
(2007/10/03)
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- Cycloaddition Routes to Tricyclo1,7.02,9>undecanes: A Direct Total Synthesis of (+)-Longifolene via an Intramolecular Diels-Alder Strategy
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The total synthesis of the sesquiterpene (+)-longifolene (1) by an intramolecular Diels-Alder cycloaddition strategy is described.Addition of methyllithium to the epoxyfulvene 13, derived from cyclopentadiene and 3,4-epoxy-2-butanone, led to an exo-tet cyclization of the resulting cyclopentadienyl anion to generate the spirohepta-4,6-diene alcohol 14.Resolution of this material was effected via its menthyl carbonate derivative 15.Oxidation of the (+)-R-alcohol with active MnO2 afforded the cyclopropyl aldehyde 16 which was condensed with the anion derived from methyl 3-methylcrotonate in the presence of cadmium chloride to gen erate the unsaturated lactone 20 or the unsaturated ester 18.Microwave heating of the silyl triene 19 effected cycloaddition to the adduct 21.Hydrogenolysis of the alcohol 22 afforded the "sinularene" skeleton 25.Cyclopropane ring cleavage of the derived ketones 23, 30, and the thiocarbonate 27 was examined but only in the Li/NH3 reduction of 30 was the longifolene skeleton 33 produced as a significant product which unfortunately could not be separated from its isomer 32.Consequently the successful route utilized regiospecific cleavage of the cyclopropane ring in the cyclopentadiene 20 in methanol catalyzed by BF3*Et2O to afford the substituted cyclopentadiene lactone(s) 34 (83percent).Cyclization proceeded smoothly, in a sealed tube, in toluene, in a microwave oven to afford the single tetracyclic adduct 39 in 97percent yield.Double bond hydrogenation and reduction of the lactone with LiAlH4 afforded the substituted longifolene skeleton, and the resulting primary alcohol was acetylated selectively to give 40.Free-radical-mediated replacement of the secondary oxygen functions was accomplished via the phenoxythiocarbonate derivative to afford the methoxy acetate 43.Alternatively the reaction sequence could b e modified to convert 39 to 41 to 42 and then to 43.Methoxy cleavage (Me3SiI) and a second free-radical reaction gave the acetate 44.Pyrolysis of this acetate (525 deg C) provided (+)-longifolene (1).
- Lei, Bo,Fallis, Alex G.
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p. 2186 - 2195
(2007/10/02)
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- NMR detection of N-acyliminium ion intermediates generated from α-alkoxycarbamates
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The N-acyliminium ion intermediates generated from α-alkoxycarbamates in the presence of Lewis acids were for the First time detected by 1 H and 13C NMR. It was confirmed that there is an equilibrium between the starting carbamate and the intermediate and that the equilibrium is highly dependent upon a Lewis acid. By using the saturation transfer method, the rate constant for the formation of the intermediate was obtained. NOE experiments revealed that ((4-methylphenyl)methylene)methyl(methoxycarbonyl)ammonium methyltrifluoroborate 6 has E-geometry.
- Yamamoto, Yoshinori,Nakada, Tomohisa,Nemoto, Hisao
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p. 121 - 125
(2007/10/02)
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- Qunoline intermediates useful therein for synthesizing antibacterial compounds
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A novel process and intermediates used therein for linking a cephalosporin compound to a quinolone are disclosed. According to the disclosed process, the 2-carboxylic acid moiety of the cephalosporin compound is treated with an organic base. The resulting salt is then reacted with a quinolone compound which has been activated using a haloformate. The reaction is run in a non-aqueous organic solvent. 4-Dimethylaminopyridine is used to promote the reaction between the cephalosporin salt and the activated quinolone.
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