Palladium-Catalyzed Asymmetric Trifluoromethylated Allylic Alkylation of N-Substituted Glycine Ethyl Esters with α-(Trifluoromethyl)alkenyl Acetates

An efficient strategy for asymmetric trifluoromethylated allylic alkylation of easily available N-substituted glycine ethyl esters with α-(trifluoromethyl)alkenyl acetates has been developed. Catalyzed by a [Pd(C₃H₅)Cl]₂/(R)-BINAP, various trifluoromethyl-containing N-substituted glycine ethyl ester derivatives are afforded with good yields and excellent enantioselectivities. The product can be readily converted into diverse fluoro-substituted species, which shows the practicability of this method.     

Unsaturated hydantoin derivatives XI. Synthesis and rearrangement of some ethyl esters of α-substituted hydantoest-δ5,α-acetic acids

α-Substituted (CH₃, C₆H₅, OCH₃, OC₆H₅, Cl, and F) hydantoin-Δ^5,α -acetates were obtained from diethyl oxaloacetates and urea, and their 3-methyl derivative s were obtained from N-methylurea or by methylation of the nitrogen-unsubstituted hydantoins with diazomethane; theα-nitro derivative was obtained by nitration of unsubstituted ethyl hydantoin-Δ^5,α -acetate with nitric acid in acetic acid, and ethyl hydantoin-Δ^5,α -glycolate was obtained from hydantoin and diethyl oxalate. All of the synthesized hydantoin-Δ^5,α -acetates, except for theα-nitro andα-hydroxy derivatives, are converted to the corresponding 3- and 5-substituted orotic acids.     

Pyrrolopyridazines. II. Synthesis of the novel pyrrolo[3,2-c]pyridazine ring system

The first derivatives of the pyrrolo[3,2-c]pyridazine ring system, ethyl pyrrolo[3,2-c]pyridazine-6-carboxylate 2-oxide (5) and ethyl 3-chloro-6-methylpyrrolo[3,2-c]pyridazine-7-glyoxalate 1-oxide ( 12 ), were obtained in good yields from the cyclization of 4-ethoxymethyl-eneamino-3-methylpyridazine 1-oxide (3) and 3-chloro-5-(α-ethoxyethylideneamino)-6-methylpyridazine 1-oxide (14, R ? Cl, R₁ ? OMe), respectively, with diethyl oxalate and potassium ethoxide in ether.     

Enzymatic Determination of Urinary Total 7α-Hydroxy Bile Acids

Abstract

An enzymatic determination of urinary 7^α-hydroxy bile acids is described. The principle of the method is as follows: after hydrolysis with β-glucuronidase and solvolysis, the ethyl acetate extract is washed with alkalin solution and water, then the alkali and water washes of the ethyl acetate extract are combined and the solution is acidified to pH 1 and sodium chloride added. Shake solution with ethyl acetate to re-extract the acidic fraction and the ethyl acetate layer is evaporated. Add enzyme color solution of 7_α-hydroxysteroid dehydrogenase (7_α-HSD, from E. coli) to a tube of extract residue and then after incubation, measure the absorbance of the solution.

Excretion values of urinary total 7_α-hydroxy bile acids was measured with patients of acute hepatitis and normal subjects and excretion pattern of 7_α-hydroxy bile acids by the use of chromatographic fractionation was also shown.     

Convenient preparation of (Z)-α-halo-α,β-unsaturated aldehydes: synthesis of a Laurencia flexilis toxin

The CrCl₂-mediated two-carbon halo-homologation of aryl, alkenyl, and aliphatic aldehydes with chloral ethyl hemiacetal or bromal affords (Z)-α-chloro- and (Z)-α-bromo-α,β-unsaturated aldehydes, respectively, in good to excellent yields and high stereoselectivity. The utility of this methodology was illustrated by a synthesis of 2-chloropentadec-2(Z)-enal, a toxin isolated from the marine red alga Laurencia flexilis.     

Synthetic Studies on Sialoglycoconjugates 23: Total Synthesis of Sialyl-α(2↠6)-Lactotetraosylceramide and Sialyl-α(2↠6)-Neolactotetraosylceramide

ABSTRACT

The first total syntheses of sialyl-α(2→6)-lactotetraosylceramide (29, IV⁶NeuAcLc₄Cer) and sialyl-α(2→6)-neolatotetraosylceramide (33, IV⁶NeuAcnLc₄Cer) are described. Methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→6)-2,4-di-O-benzoyl-3-O-benzyl-1-thio-ß-D-galactopyranoside (11), the key glycosyl donor was prepared, via glycosylation of 2-(trimethylsilyl)ethyl 3-O-benzyl-ß-D-galactopyranoside (2) with the methyl α-thioglycoside 3 of N-acetylneuraminic acid, benzoylation, replacement of the 2-(trimethylsilyl)ethyl group by acetyl, and introduction of the methylthio group with (methylthio)trimethylsilane. Each coupling of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-ß-D-glucopyranosyl)-(1→3′)-per-O-benzyl-ß-lactoside (12) or 2-(trimethylsilyl)ethyl O-(2-acetamido-3-O-acetyl-6-O-benzyl-2-deozy-ß-D-glucopyranosyl)-(1→3′)-per-O-benzyl-ß-D-lactoside (14) prepared from 12 by O-acetylation and reductive opening of the benzylidene acetal, with 11 gave the pentasaccharides 16 and 20 in good yields. Compounds 16 and 20 were converted into the corresponding α-trichloroacetimidates 19 and 24 which, on coupling with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (25), gave the ß-glycosides 26 and 30, respectively. Finally, 26 and 30 were transformed, via selective reduction of the azide group, condensation with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester group, into 29 and 33, respectively.     

The synthesis of methyl N,N′-diacetyl-α-d-kasugaminide

The synthesis of methyl N,N′-diacetyl-α-d-kasugaminide (24) has been described. 3 was converted through hydroboration-amination to ethyl 4-acetamido-2, 3, 4, 6-tetradeoxy-α, β-dl-glucopyranosides (ethyl N-acetyl-αβ-dl-tolyposaminide) (7 and 8). Bromination of 7 and 8 gave the 2-bromo compounds (17, 18 and 19). Displacement of Br of 17 with N₃ and subsequent hydrogenation and resolution furnished d-kasugaminide. Synthesis of ethyl α-dl-forosaminide has also been described.     

Concise synthesis of enantiopure (S)- and (R)-α-trifluoromethyl aspartic acid and α-trifluoromethyl serine from chiral trifluoromethyl oxazolidines (Fox) via a Strecker-type reaction

A concise synthesis of enantiopure (S)- and (R)-α-Tfm-aspartic acid and α-Tfm-serine is reported. The key step involves a Strecker-type reaction on chiral CF₃-oxazolidines (Fox) derived from ethyl 4,4,4-trifluoroacetoacetate (ETFAA) or ethyl trifluoropyruvate.     

Stereoregularity of poly(α-methylvinyl alkyl ether)s determined by 1H- and 13C-NMR spectroscopy

α-Methylvinyl methyl ether, ethyl ether, and isobutyl ether were polymerized under various polymerization conditions and the structure of the polymers was determined by ¹H- and ¹³C-NMR spectroscopy. α-Methyl and β-methylene carbon spectra of poly(α-methylvinyl isobutyl ether) showed splitting and were analyzed by triad and tetrad sequences. β-Methylene carbon spectra of poly(α-methylvinyl ethyl ether) also showed splitting. When Eu(fod)₃ was added, α-methyl and methoxy proton spectra in benzene of poly(α-methylvinyl methyl ether) showed splitting assigned to triad tacticities. All the polymers obtained in polar solvents exhibited an increase in syndiotacticity. The polymerization mechanism is discussed.     

Highly active Pd-Fe/α-Al_2O_3 catalyst with the bayberry tannin as chelating promoter for CO oxidative coupling to diethyl oxalate

A novel Pd-Fe/α-Al_2O_3 catalyst was synthesized by incipient-wetness impregnation method with bayberry tannin as chelating promoter and commercial hollow column Raschig ring a-Al_2O_3 as support for the synthesis of diethyl oxalate from CO and ethyl nitrite.A variety of characterization techniques including N_2 physical adsorption,optical microscopy,scanning electron microscopy and energy dispersive system(SEM-EDS),inductively coupled plasma optical emission spectroscopy(ICP-OES),X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),transmission electron microscopy(TEM),were employed to explore the relationship between the physicochemical properties and activity of catalysts.It indicated that a large number of phenolic hydroxyl groups in bayberry tannin can efficiently anchor the active component Pd,reduce the particle size and make the active Pd as a multi-ring distribution on the commercial a-Al_2O_3 suppo rt,which we re beneficial to improve the catalytic activity for the production of diethyl oxalate from CO and ethyl nitrite.0.3 wts Pd-Fe/α-Al_2O_3 showed excelle nt catalytic activity and selectivity in a continuous flow,fixed-bed reactor with the loading amount of 10 mL catalysts,Under the mild reaction conditions,the space-time yield of diethyl oxalate was 978 g L ~1 h ~1 and CO conversion was 44% with the selectivity to diethyl oxalate of 95.5%.     

Synthesis of bulky tris[(dimethyl(alkyl/aryl)silyl)methyl]stannanes as radical based reducing agents

The synthesis of novel bulky tris[dimethyl(ethyl/benzyl/p-tolyl/α-naphthyl)silylmethyl]stannanes (1-4) is described. Alkylation of SnCl₄ with Me₂(ethyl/p-tolyl)SiCH₂MgBr (10-11) gave mainly the triorganotin chlorides [(Me₂(ethyl/p-tolyl)SiCH₂)]₃SnCl 14 and 15, which were isolated by silica gel chromatography. Reduction of 14 and 15 with LiAlH₄ in THF gave the corresponding triorganotin hydrides 1 and 2, respectively. [Me₂(benzyl/α-naphthyl)SiCH₂]₃SnCl 16 and 17, generated by the alkylation of SnCl₄ with Me₂(benzyl/α-naphthyl)SiCH₂MgBr 12 and 13, were inseparable from the minor product [Me₂(benzyl/α-naphthyl)SiCH₂]₂SnCl₂18 and 19, respectively. Treatment of the mixtures of 16/18 and 17/19 with NaOH furnished the corresponding mixtures of stannoxanes, from which the hexakisdistannoxanes [Me₂(benzyl/α-naphthyl)SiCH₂]₆Sn₂O 20 and 22 were isolated from the minor dialkyltin oxide derivatives [Me₂(benzyl/α-naphthyl)SiCH₂]₂SnO in good yields. Reduction of 20 and 22 with BH₃ in THF gave [Me₂(benzyl/α-naphthyl)SiCH₂]₃SnH (3 and 4), respectively in good yields. ¹H, ¹³C, ¹¹⁹Sn, ²⁹Si NMR characteristics of the newly synthesized compounds are included.     

MgCl2/Et3N催化合成α,β-不饱和氰代酯

用MgCl₂/Et₃N催化氰乙酸乙酯和芳香醛的缩合反应合成α,β-不饱和氰代酯, 反应可在室温进行. 产率87%～92%.     

Phytoecdysteroids ofRhaponticum carthamoides

From the roots with rhizomes of the plantRhaponticum carthamoides Willd) Iljin Compositae), in addition to integristerone A, ecdysterone, polypodin B, 2-deoxyecdysterone, and 24(28)-dehydromakisterone A, we have isolated the new compounds ecdysteron3–2,3-monoacetonide (I), ecdysterone 20,22-monoacetonide (II)) and rhapisterone (III): I — C₃₀H₄₈O₇, mp 232–233° (ethyl acetate-methanol) [α] _D ²⁰ +56.4±2° (c 0.0; methanol); II — C₃₀H₄₈O₇, mp 227–229° (ethyl acetate-methanol), [α] _D ²⁰ +60.1±2° (c 1.3; methanol); III — C₂₉H₄₈O₇, mp, 241–242° (ethyl acetate-methanol), [α] _D ²⁰ +30±2° (c 0.1; dioxane). The structure of (III) was established on the basis of spectral characteristics as 2β, 3β, 14α, 20R, 22R, 23ζ-5β-stigmast-7-en-6-one. Details of the PMR, mass, and IR spectra of all the compounds and of the CD of rhapisterone are given.     

2,4,6‐Tri­methyl­phenol

Crystals of the title compound, C₉H₁₂O, were formed as an unexpected by‐product during the recrystallization of (2R,3R)‐α,α,α′,α′‐tetramesityl‐1,4‐dioxa­spiro­[4,5]­decane‐2,3‐di­methanol from hexane/ethyl acetate (7:3). Strong hydrogen bonds between hydroxide groups connect the mol­ecules around one set of four symmetry‐equivalent 2₁ axes.     

Reactions of Enaminones with Diazocarbonyl Compounds

The [Cu(acac)₂]‐catalyzed reactions of several tertiary enaminones with three diazocarbonyl compounds, i.e., dimethyl diazomalonate, ethyl diazoacetoacetate, and ethyl diazoacetate, yielded amino‐ and additionally carbonyl‐substituted dihydrofurans, together with further furan derivatives. Due to the conjugation of α‐carbonyl/α‐Ph groups, reactions proceeded only via 1,5‐electrocyclization of corresponding keto‐ylides. On the other hand, in the absence of any α‐substituent, tertiary enaminone and ethyl diazoacetate, reacted via an accompanying mechanism by a push‐pull cyclopropane intermediate, to yield a 2,4‐dicarbonyl‐substituted furan in one step with moderate yield.     

Stereocontrolled palladium(0)-catalyzed preparation of unsaturated azidosugars: an easy access to 2- and 4-aminoglycosides

The palladium-catalyzed substitution of alkyl 4,6-di-O-acetyl-α-d-erythro-hex-2-eno-pyranosides using NaN₃ as the nucleophile gave predominantly the corresponding alkyl 2-azido-2,3,4-trideoxy-α-d-threo-hex-2-enopyranosides in the presence of Pd(PPh₃)₄. However, alkyl 6-O-acetyl-4-azido-2,3,4-trideoxy-α-d-erythro-hex-2-enopyranosides were obtained as the major products using Pd(PPh₃)₄ as the catalyst in the presence of dppb as the added ligand. Conversely, alkyl 6-O-(tert-butyldimethylsilyl)-4-O-methoxycarbonyl-2,3-dideoxy-α-d-hex-2-enopyranosides gave exclusively alkyl 4-azido-6-O-(tert-butyldimethylsilyl)-2,3,4-trideoxy-α-d-erythro-hex-2-enopyranosides in the presence of Pd₂(dba)₃/PPh₃ as the catalyst and Me₃SiN₃ as the nucleophile. The bis-hydroxylation followed by hydrogenation of ethyl 4-azido-2,3,4-trideoxy-α-d-erythro-hex-2-enopyranoside afforded the corresponding 4-amino-α-d-mannopyranoside, when propyl 2-azido-2,3,4-trideoxy-α-d-threo-hex-3-enopyranoside gave the 2-amino-α-d-altropyranoside under the same conditions.     

Facile preparation of aromatic esters from aromatic bromides with ethyl formate or DMF and molecular iodine via aryllithium

Various aromatic bromides were treated with n-BuLi and subsequently with ethyl formate, followed by the reaction with ethanol and molecular iodine in the presence of K₂CO₃ to provide the corresponding aromatic ethyl esters in good yields. Moreover, aromatic bromides could be transformed into the corresponding aromatic methyl esters in good yields by the treatment with n-BuLi and subsequently with DMF, followed by the reaction with methanol, molecular iodine, and K₂CO₃. Some aromatics could be also converted into the corresponding aromatic esters in good yields by the treatment with n-BuLi, and subsequently with ethyl formate or DMF, followed by the reaction with molecular iodine and K₂CO₃. The present reactions offer a novel route for the transition-metal-free, carbon-monoxide-free, and therefore environmentally benign one-pot conversion of aromatic bromides and aromatics into aromatic esters.     

Reactions of terpene alcohols and diols with chlorine dioxide in dimethylformamide

The system chlorine dioxide–dimethylformamide in combination with or without a catalytic amount of MoCl₅, CeCl₃, ZrOCl₂, or VO(acac)₂ induces oxidative chlorination of a number of bicyclic terpene alcohols and vicinal diols. 2α-Chloropinan-3-one, 3α-chloro-10β-pinan-4-one, 5α-chloro-3α-hydroxycaran-4-one, 5β-chloro-3β-hydroxycaran-4-one, and 4α-chloro-2α-hydroxypinan-3-one were thus synthesized in good preparative yields.     

Concise access to enantiopure (S)- and (R)-α-trifluoromethyl pyroglutamic acids from ethyl trifluoropyruvate-based chiral CF3-oxazolidines (Fox)

A straightforward synthesis of enantiopure (S)- and (R)-α-Tfm-pyroglutamic acid is reported. The strategy is based on the use of a chiral CF₃-hydroxymorpholinone intermediate conveniently obtained from ethyl trifluoropyruvate-based chiral CF₃-oxazolidines (Fox). The key step is an oxidative cyclization followed by a reductive cleavage of the (R)-phenylglycinol chiral auxiliary.     

双二茂铁甲基碳正离子与乙酰乙酸乙酯的反应及其产物的晶体结构

双二茂铁甲醇与BF₃•OEt₂ 在CH₂Cl₂中作用形成稳定的双二茂铁甲基碳正离子, 无需从溶液中分离, 可直接与乙酰乙酸乙酯反应得到了较高产率的双二茂铁甲基乙酰乙酸乙酯. 由苯重结晶得到的单晶经过X射线衍射测试发现, 该化合物属于三斜晶系, 空间群P , a＝0.82554(8) nm, b＝0.96962(10) nm, c＝1.46662(14) nm, α＝105.562(2)°, β＝90.771(2)°, γ＝96.727(2)°, V＝1.2191(19) nm³, D_c＝1.516 g•cm^－3, μ＝1.320 mm^－1, F(000)＝532, Z＝2.