Novel approach towards one pot stereospecific synthesis of carbohydrate derived substituted imidazolines

A simple synthetic approach has been developed towards one pot synthesis of 2-imidazolines under mild acidic conditions from N-acetyl glucosamine via reductive amination followed by dehydrative cyclization. Synthetic studies were explored in detail with different amines and sugar derivatives. While the conversion was good, the corresponding substituted imidazolines were obtained in moderate yields.     

Preparative synthesis of heterocyclic and aromatic N-benzyl amines

A simple and highly efficient procedure has been proposed for the synthesis of heterocyclic and aromatic N-benzyl amines via reductive amination of substituted aromatic aldehydes in the presence of sodium tetrahydridoborate-acetic acid system generating reactive sodium triacetoxyhydridoborate.     

Convenient synthesis of 1,3-substituted-6-phenylpiperazin-2-ones

The convenient preparation of novel 6-phenylpiperazin-2-ones from simple starting materials via a practical two-step procedure is presented. This methodology involves an initial alkylation of 2-bromoacetophenone with an amino ester followed by a one-pot reductive amination and cyclization step to furnish the desired substituted piperazinones.     

Furan compounds

By reductive amination, starting from furfural, 5-methylfurfural, β-(2-furyl)acrolein, and monoethanolamine, we have obtained N-furfurylaminoethanol, N-(5-methyl-2-furfuryl)aminoethanol, and N-[1-(α-furyl)-3-propyl]aminoethanol. By reductive amination combined with the subsequent hydrogenation of the furan ring we have obtained N-tetrahydrofurfurylaminoethanol and N-(5-methyltetrahydro-2-furfuryl)aminoethanol.     

General Synthesis of 1‐Substituted 2‐Methylbenzimidazoles from Ketones and 2‐Aminoacetanilide

A novel method for preparation of 1‐substituted benzimidazoles via reductive amination of ketones with N‐differentiated 1,2‐diaminobenzenes is described. The method appears to be general in application to acyclic and cyclic ketones, as well as heteroatom‐substituted cyclic ketones.     

A one-pot synthetic approach to the functionalized isomeric ellipticine derivatives through an imino Diels-Alder reaction

An efficient, three component, one-pot synthesis of new isomeric ellipticine derivatives prepared through an imino Diels-Alder reaction of 3-aminocarbazoles and substituted benzaldehydes with electron-rich alkenes such as 3,4-dihydro-2H-pyran, 2,3- dihydrofuran and ethyl vinyl ether catalyzed by InCl₃ (10 mol %) in ionic liquid is reported. In the case of substituted benzaldehydes, reductive amination is observed.     

A versatile PIFA-mediated approach to structurally diverse pyrrolo(benzo)diazepines from linear alkynylamides

The addition of the hypervalent iodine reagent PIFA [phenyliodine(III) bis(trifluoroacetate)] to a series of properly substituted N-(3-aminopropyl)alkynylamides results in the efficient formation of a functionalized 5-aroyl-2-pyrrolidinone skeleton. By proper manipulations of the N(1)-substituents, through consecutive deprotection and/or reductive amination steps, a second cyclization process occurs yielding the target heterocycles. As it will be disclosed, the overall process is open to structural modifications that gives rise to a series of pyrrolo(benzo)diazepine derivatives.     

Reductive amination of furfural toward furfurylamine with aqueous ammonia under hydrogen over Ru-supported catalyst

Poly(N-vinyl-2-pyrrolidone)-capped ruthenium-supported hydroxyapatite (Ru-PVP/HAP) shows significant activity for the synthesis of furfurylamine (FAM) via the reductive amination of furfural. As-prepared 5 wt% Ru-PVP/HAP affords 50 % yield of FAM in 25 % NH₃ aqueous solution under pressurized H₂ gas (2.5 atm), and the highest yield approaches 60 % at 4.0 H₂ atm. Comparison between the activities over four Ru-supported HAP catalysts prepared with different methods and the results of X-ray absorption spectroscopy suggested that the metallic Ru cluster is the active center for the reductive amination of furfural. Transmission electron microscope and inductively-coupled plasma analysis indicated that the as-prepared 5 wt% Ru-PVP/HAP catalyst possessed 4.0 wt% PVP-capped Ru clusters with average diameter of 1.7 ± 0.3 nm on HAP support. It was also demonstrated that the reductive amination approach with Ru-PVP/HAP catalyst, NH₃ aq. and pressurized H₂ gas has capability for transformation of aromatic aldehydes to the corresponding aromatic amines. According to these results, it is concluded that Ru(0) cluster supported on HAP will represent a suitable catalyst for widely-usable reductive amination to convert an aldehyde functionality towards an amine.     

Lithium borohydride: a reagent of choice for the selective reductive amination of cyclohexanones

Traditional reductive amination of substituted cyclohexanones are either selective toward the formation of cis-products or show low selectivity. Herein we report a selective procedure for the reductive amination of substituted cyclohexanones with primary amines using lithium borohydride that is selective toward formation of trans-products.     

Redox Amination Scope of Benzylic Ketones with Indoline: Synthetic and Mechanistic Insights

Bi(NO₃)₃·5H₂O‐Catalyzed redox amination scope and mechanistic insights of benzylic ketones with indoline are discussed. The experimental results demonstrate that the formation of N‐alkyl‐substituted indole/indoline derivatives over typically competitive redox and reductive amination processes is depending upon the reaction condition for the benzylic ketones.     

Brevibacterium epidermidis催化酮不对称还原胺化合成(S)-手性胺

光学纯手性胺是一类非常重要的手性化学品,作为手性砌块和手性拆分剂广泛用于医药、农业化学品、精细化学品等产品的合成中.据统计,美国FDA近年来批准的约40％药物中都含有一个或多个手性胺结构单元.胺脱氢酶(AmDH)是由氨基酸脱氢酶改造而来的一类催化酮不对称还原胺化的新酶,其在手性胺的合成中展现出较强的潜力,已引起国内外学术界和工业界的广泛关注.这是因为该酶能够利用廉价的无机铵为胺供体,且具有催化效率高、原子经济性好和环境友好等优点.迄今为止已经有数个高效的胺脱氢酶被成功开发和报道,但是这些通过蛋白质工程改造的胺脱氢酶均为(R)-选择性,因此只能合成(R)-选择性的手性胺,遗憾的是还未见有(S)-选择性胺脱氢酶的报道.因此,本文主要目的是期望从自然环境中鉴定能够不对称还原胺化酮合成(S)-手性胺的微生物,进而从中分离得到能够以无机铵作为胺供体合成(S)-手性胺的(S)-选择性酶.本文首先利用苯乙胺作为唯一氮源,从土壤中筛选能够利用苯乙胺生长的菌株,进而利用苯乙酮作为初筛底物对得到的菌株进行胺化能力筛选,再利用(4-氟苯基)丙酮作为模式底物进行进一步的筛选.幸运的是,我们获得了能够利用无机铵作为胺供体催化(4-氟苯基)丙酮不对称还原胺化合成(S)-4-氟-α-甲基苯乙胺的菌株,经过16S RNA鉴定为表皮短杆菌,命名为B.epidermidis ECU1015.接下来,我们对B.epidermidis ECU1015催化的胺化反应中的关键参数如胺基供体及其最适浓度、反应温度、pH值和底物浓度等进行了优化,确定最佳反应条件:胺供体为NH4Cl(1.25 mol/L),反应温度为30°C,KPB缓冲液(200 mmol/L,pH 7.5),底物浓度10 mmol/L.最后,在最适的反应条件下,我们对B.epidermidis ECU1015催化的底物谱进行了研究.结果表明,该微生物不能催化大位阻芳香酮和链状酮的胺化,对位阻较小的苯乙酮及(4-氟苯基)丙酮具有较好的还原胺化能力,而且对苯环上带有吸电子取代基的酮化合物具有更好的转化效果.经手性分析,所有生成的手性胺均为(S)-构型,产品的光学纯度均>99％.B.epidermidis催化酮不对称胺化所形成的产物构型均为(S)-选择性,这不同于已报道的(R)-选择性胺脱氢酶.该菌株的发现为(S)-选择性胺脱氢酶的进一步鉴定奠定了一定的研究基础,相关蛋白的分离纯化工作正在进行.     

Controlling stereoselectivity by enzymatic and chemical means to access enantiomerically pure (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinoline derivatives

A chemoenzymatic strategy for the synthesis of enantiomerically pure novel alkaloids (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinolines is presented. The key steps are the biocatalytic stereoselective reductive amination of substituted 1-phenylpropan-2-one derivatives to yield chiral amines employing microbial ω-transaminases, and the diastereoselective reduction of a Bischler–Napieralski imine intermediate by catalytic hydrogenation in the presence of palladium on charcoal, leading exclusively to the desired cis-isomer.     

Functionalization of bicyclic 2-pyridones targeting pilus biogenesis in uropathogenic Escherichia coli

Substituted bicyclic 2-pyridones, termed pilicides, prevent pilus assembly in uropathogenic Escherichia coli. Based on the bioactive methyl ester protected 2-pyridone 4, further functionalization at C-6 has yielded a set of new compounds, which have been evaluated for their ability to inhibit pilus formation in uropathogenic E. coli. The key intermediate in the synthesis was formylated 2-pyridone 5, which could be obtained via a Vilsmeier reaction. This versatile intermediate was converted into secondary and tertiary amines via reductive amination and could also be converted to other interesting functionalities using simple chemical transformations.     

Concise synthesis of pyrrolidine and indolizidine alkaloids by a highly convergent three-component reaction

The synthesis of pyrrolidine and indolizidine derivatives through radical carboazidation of alkenes with α-iodoketones, followed by reductive amination, is described. When properly substituted, further lactamization afforded pyrrolizidinones in good yield. This carboazidation/reductive amination sequence was efficiently applied to the total synthesis of three different simple alkaloids, including (±)-monomorine I.     

Synthesis of bicyclic azacompounds (3‐dimethylcarbamoyloxyphenyl) substituted as acetylcholinesterase inhibitors

This paper describes the synthesis of some bicyclic 2‐(3‐dimethylcarbamoyloxyphenyl) substituted azaderivatives, obtained from 1,4‐ and 1,5‐diketones, which were cyclized with ammonium acetate, methylamine and by reductive amination. Corresponding 3‐substituted derivatives were instead prepared by reaction of 1,5‐ketoesters with formamide. The carbamates were tested as in vitro acetylcholinesterase inhibitors.     

负载型Ni催化剂高效催化2-羟基四氢吡喃还原胺化制备5-氨基-1-戊醇（英文）

伯胺等含氮化合物是最重要的化工中间体之一,被广泛应用于聚合物、医药、农药、染料和表面活性剂等产品的生产.当前,商业化伯胺主要通过卤代烃或环氧化合物直接胺化以及腈类或酰胺类化合物加氢制备,这些过程受具有特定官能团的有机原料短缺以及产生较多废物等问题的限制,导致其生产成本较高.因此,高效可持续生产伯胺化合物路径的开发得到了广泛关注.醛和酮类化合物直接与氨还原胺化反应所需温度一般较低(≤120℃),为伯胺的高选择性合成提供了一个重要途径.基于此,本文利用2-羟基四氢吡喃能够原位转化为其互变异构体5-羟基戊醛,而5-羟基戊醛中醛基具有较高还原胺化活性的特征,发展了一种以生物糠醛衍生二氢吡喃为原料,通过先水合得到2-羟基四氢吡喃再在温和条件下还原胺化合成5-氨基-1-戊醇的新方法.5-氨基-1-戊醇是一种分子中同时含有羟基和氨基的重要双官能团化合物,广泛用于医药和农药合成,也常被用作有机合成砌块,目前其主要用途是合成具有很高药用价值的生物碱Manzamine A.5-氨基-1-戊醇的一条传统合成路线是以石化基1,5-戊二醇经浓盐酸进行单氯取代制备5-氯戊醇中间体,该中间体经分离后再与氨气反应制得5-氨基-1-戊醇的方法.该方法原料成本高,产生大量废弃物,且只取得中等目标产物收率(66.6%).本文重点研究了不同氧化物载体包括SiO2,TiO2,γ-Al2O3,ZrO2和MgO负载Ni催化剂的2-羟基四氢吡喃还原胺化性能,并对比考察了CuCr2O4,雷尼Ni,Ru/C,Pd/C,Pt/C和Rh/C等商业加氢催化剂的性能.研究发现,ZrO2负载Ni催化剂的活性高于其他氧化物载体负载Ni催化剂的活性,也明显优于所对比的系列商业加氢催化剂.系列物理化学表征结果显示,Ni/ZrO2催化剂同时表现出较高的还原性和表面酸密度,这可能是该催化剂表现出最高5-氨基-1-戊醇收率的原因.以Ni/ZrO2为催化剂,于80℃,2 MPa H2条件下在间歇式反应器中催化2-羟基四氢吡喃水溶液还原胺化可取得90.8%的5-氨基-1-戊醇收率.通过固定床反应器研究了Ni/ZrO2催化剂稳定性,发现5-氨基-1-戊醇初始收率可达83%,反应90 h活性缓慢下降至初活性的81%.Ni流失和表面氧化可能是催化剂的失活的主要原因.通过对反应温度、H2压力、2-羟基四氢吡喃/NH3摩尔比等因素对反应活性调变规律的探究,推测2-羟基四氢吡喃催化还原胺化制备5-氨基-1-戊醇反应机理如下:首先,受化学平衡作用,2-羟基四氢吡喃逐渐转化为其互变异构体5-羟基戊醛;然后,5-羟基戊醛中醛基迅速与NH3反应生成亚胺中间体;最后,亚胺中间体在金属催化剂上加氢得到5-氨基-1-戊醇.     

Reaction of primary amines with Pt/C catalyst in water under microwave irradiation: a convenient synthesis of secondary amines from primary amines

Upon microwave irradiation in water, Pt/C converts primary amines into secondary amines in good yield via retro-reductive and reductive amination.     

Synthetic route towards (5R,2′S,5′S,6′S)-ribosyl-diazepanone,an analogue core of the liposidomycins

The synthesis of (5R,2′S,5′S,6′S)-ribosyl-diazepanone, an analogue core of liposidomycins is described. The core ribosyl seven-membered heterocycle of nucleoside antibiotic liposidomycins was formed by reductive amination of an α-ribosylamino ester derived from d-ribose, and an amino aldehyde derived from methyl 4-triisopropylsilyloxy-3-oxobutanoate, followed by a peptidic coupling reaction.     

Synthesis of C8-glycomimetics as potential glycosidases inhibitors

The synthesis of C8-glycomimetics is described from C₂-symmetrical polyhydroxylated cyclooctenes derived from carbocyclisation of enantiomerically pure 1,9-dienes by ring closing metathesis. Their obtention notably involved either hydroboration followed by oxidation to carbasugars or to cyclooctanones then reductive amination, or formation of a cis-cyclic sulfate followed by successive introduction of an azido group, reduction and subsequent reductive amination. The biological activity of the C8-carbasugars and related aminocyclitols, analogous to voglibose, has been evaluated towards several commercially available glycosidases.     

Solid-phase synthesis of 2-imidazolidinethiones via Mitsunobu reaction of N-(2-hydroxyethyl)thioureas

This letter reports the solid-phase synthesis of 2-imidazolidinethiones via the N-cyclization of N-(2-hydroxyethyl)thioureas using the Mitsunobu reaction in good yield and purity. This process employed the reductive amination of an ArgoGel-MB-CHO resin to anchor the aminoalcohols, followed by a reaction with isothiocyanates to give the resin-attached N-(2-hydroxyethyl)thioureas. Cleavage of the 2-imidazolidinethiones was performed with trifluoroacetic acid.