Synthesis of tetrazole analogues of amino acids using Fmoc chemistry: isolation of amino free tetrazoles and their incorporation into peptides

An efficient synthesis of tetrazole analogues of amino acids starting from N^α-Fmoc amino acid in a three-step protocol is reported. The free amino tetrazoles were obtained in good yields and with excellent purity after removal of the Fmoc group. The synthesis of analogues of aspartic and glutamic acids in which the 5-tetrazolyl moiety is inserted at the β/γ carboxyl group starting from Fmoc-Asn and Fmoc-Gln and the incorporation of these tetrazoles into peptides are also described.     

Kinetic study of the reaction of nucleophilic cyclopropanation of C60 fullerene with halogenated maleopimarimide

The kinetics of nucleophilic fullerene cyclopropanation by halomethyl ketones with a diterpene fragment has been studied by the Bingel method, and the influence of the biologically active cyclopropanating agent on the process has been estimated. It has been revealed that favorable conditions for carrying out the reaction result in maximum monofunctionalized methanofullerenes formation with the maximum yield.     

Asymmetric Catalytic Synthesis of Hexahydropyrrolo-isoquinolines via Three-Component 1,3-Dipolar-Cycloaddition

An asymmetric three-component 1,3-dipolar cycloaddition of 3,4-dihydroisoquinolines, bromoacetates and α,β-unsaturated pyrazole amide is realized by using a chiral N,N’-dioxide-Y(OTf)₃ complex as the catalyst. The process includes a base-promoted formation of dihydroisoquinolium ylides in situ, and a chiral Lewis acid-catalyzed asymmetric [3+2] cycloaddition with α,β-unsaturated pyrazole amides. A series of hexahydropyrrolo-isoquinolines are obtained in moderate to good yields with excellent diastereo- and enantioselectivities.     

Synthesis of ethyl 4-chloro-2-oxobut-3-ynoate and its addition to alkyl vinyl ethers

Ethyl 4-chloro-2-oxobut-3-ynoate has been synthesized for the first time and its addition to alkyl vinyl ethers of various structures has been studied. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1537–1539, July, 2008.     

Stereoselective Insertion of Benzynes into Lawsones: Synthesis of Biologically Important Benzannulated Bicyclo[3.3.0]octanes

An ideal stereoselective insertion of in situ generated benzynes into lawsones through domino formal [2+2]-cycloaddition followed by rearrangement is disclosed. The reaction allowed for the preparation of biologically important benzannulated bicyclo[3.3.0]octanes in good yields and with excellent selectivities by using simple substrates and conditions.     

Synthesis of polycyclic cyclopropanecarboxylic acids and their esters based on catalytic cyclopropanation of 6,6-dimethylfulvene

Reactions of 6,6-dimethylfulvene with methyl diazoacetate in the presence of Cu compounds is accompanied by methoxycarbonylmethylenation of the endocyclic double bonds to give the corresponding mono- and diadducts in total yields of up to 85% with marked predominance ofanti-isomers. The subsequent cyclopropanation of monoadducts with diazomethane in the presence of Pd compounds also involves the endocyclic double bond and gives esters of tricyclo[4.1.0.0.^2,4]heptanecarboxylic acid in high yields. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 528–531, March, 1997.     

Synthesis of 8-substituted bicyclo[3.2.1]octane-6-carboxylic acids and anti-convulsant properties of the corresponding amides

Novel 8-substituted bicyclo[3.2.1]octane-6-carboxylic acids have been made via [3+2]cycloaddition to alkyne 2. A number of the corresponding amides are anti-convulsant in mice.     

Copper-Catalyzed Synthesis of 5-Aryl-6-(Trifluoromethyl)-2,3-Dihydropyrazolo[1,2-a]Pyrazol-1(5H)-One

An efficient protocol for the synthesis of 5-aryl-6-(trifluoromethyl)-2,3-dihydropyrazolo[1,2-a]pyrazol-1(5H)-one derivatives through a copper-catalyzed [3+2]-cycloaddition of azomethine imines with 3,3,3-trifluoropropyne (generated in situ from dehydrobromination of 2-bromo-3,3,3-trifluoropropene under base conditions) is developed. The advantages of this transformation are the broad substrate scope and the good functional group compatibility. The subsequent oxidation and nucleophilic substitution/aromatization provide a new approach to 4-trifluoromethylated pyrazol-1-yl propanoic acids.     

Catalytic Asymmetric Synthesis of Benzobicyclo[3.2.1]octanes

Lawsone aldehydes were directly transformed into the biologically important, unique carbon skeleton of chiral methanobenzo[f]azulenes/methanodibenzo[a,d][7]annulenes in high dr and ee and in very good yields by using quinine-thiourea-catalyzed tandem Wittig/intramolecular Michael/intramolecular aldol reactions. This asymmetric catalytic tandem protocol will be highly useful because these final molecules are basic skeletons of important antibiotics.     

N-丁基-4-[乙基-(3-甲基苯基)氨基]丁酰胺的合成

以γ-丁内酯为起始原料,经开环氯化和酰化反应制得N-丁基-4-氯丁酰胺(2);2与N-乙基间甲苯胺经N-烷基化反应合成了N-丁基-4-[乙基-(3-甲基苯基)氨基]丁酰胺,总收率74.6%,纯度97.6%,其结构经1H NMR和MS(ESI)确证。     

Synthesis of unnatural amino acids containing the 3,7-diazabicyclo-[3,3,1]nonane unit

Unnatural amino acids containing the 3,7-diazabicyclo[3,3,1]nonane unit were synthesized in one step by the reaction of diethyl 3-oxoglutarate, bis(methoxycarbonylmethyl) sulfone, with formaldehyde and primary amino acids under conditions of the Mannich reaction. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1236–1244, August, 2008.     

Organocatalytic Formal Intramolecular [3+2]-Cycloaddition to Acquire Biologically Important Methanodibenzo[a,f]azulenes and Methanobenzo[f]azulenes

Lawsones were transformed into the functionally rich framework of methanodibenzo[a,f]azulenes and methanobenzo[f]azulenes in a single- or two-pot operation through five organocatalytic sequential reactions in very good yields with excellent selectivities. These resultant molecules are basic skeletons of important antibiotics, which highlights the value of this formal intramolecular [3+2]-cycloaddition as a key protocol.     

1，1＇－双［1－（芳亚氨基）乙基］二茂铁的合成及其环汞化反应

合成了１１种１，１＇－双［１－（芳亚氨基）乙基］二茂铁（简称二茂铁双亚胺）（ｌａ—１ｋ）和８种环汞化反应产物，用元素分析、ＩＲ、１ＨＮＭＲ确定了它们的结构；除１ｃ外，其余均为新化合物。双亚胺的环汞化反应表明主要生成单汞化产物，且汞化反应发生在取代茂环的邻位，但产率较低。探讨了影响环汞化反应的因素。     

1-氮杂-2,8-二氧杂二环[3.3.0]-辛烷类化合物合成的新方法

以苯基-3,5-二(甲氧基羰基)-2-异(口恶)唑啉-N-氧化物为偶极体,丙烯酸乙酯为亲偶极体,通过[3+2]环加成反应,简便地合成了含有多官能团的1-氮杂-2,8-二氧杂二环[3.3.0]-辛烷类化合物。该反应条件温和,产率较高(50%～93%).化合物的结构经元素分析,¹H NMR,¹³C NMR,IR和MS确认和表证,并对其波谱性质进行了讨论。     

Asymmetric [3+2]-Cycloaddition of Morita–Baylis–Hillman Carbonates with Maleimides Catalyzed by Chiral Ferrocenylphosphines

New chiral ferrocenylphosphines LB1–LB9 were designed and prepared through simple synthetic approaches. These air-stable ferrocenylphosphines were applied to promote asymmetric [3+2]-cycloaddition of Morita–Baylis–Hillman carbonates with maleimides, among which LB7 was shown to have good catalytic activity to afford the corresponding multifunctional cyclopentenes in up to 59% yield and up to 53% ee under mild reaction conditions. A plausible reaction mechanism was proposed.     

Stereoselective Synthesis of Tropanes via a 6π‐Electrocyclic Ring‐Opening/ Huisgen [3+2]‐Cycloaddition Cascade of Monocyclopropanated Heterocycles

The synthesis of tropanes via a microwave‐assisted, stereoselective 6π‐electrocyclic ring‐opening/ Huisgen [3+2]‐cycloaddition cascade of cyclopropanated pyrrole and furan derivatives with electron‐deficient dipolarophiles is demonstrated. Starting from furans or pyrroles, 8‐aza‐ and 8‐oxabicyclo[3.2.1]octanes are accessible in two steps in dia‐ and enantioselective pure form, being versatile building blocks for the synthesis of pharmaceutically relevant targets, especially for new cocaine analogues bearing various substituents at the C‐6/C‐7 positions of the tropane ring system. Moreover, the 2‐azabicyclo[2.2.2]octane core (isoquinuclidines), being prominently represented in many natural and pharmaceutical products, is accessible via this approach.     

新型杯[4]芳烃衍生物的合成及其氨基酸萃取性能

杯[4]-1,3-二乙酸乙酯衍生物(1)与水合肼反应生成杯[4]芳烃酰肼衍生物(2),化合物(2)与异硫氰酸苯酯反应得到含酰胺和硫脲单元的新型杯[4]芳烃衍生物(3).总产率达70%.系列氨基酸萃取实验表明化合物(3)对异亮氨酸有较好的选择性萃取能力.     

Synthesis and unusual [2+2]-cycloaddition reactions of ethyl 4-chloro-2-oxobut-3-ynoate with unactivated alkenes

The highly activated acetylenes, ethyl 4-chloro-2-oxobut-3-ynoate and ethyl 4-bromo-2-oxobut-3-ynoate, were prepared from readily available bis(trimethylstannyl)acetylene in two steps with high overall yield. An unusual ability of the former to furnish [2+2]-cycloadducts with 1,1-disubstituted alkenes in the absence of irradiation and catalysts was discovered. The cycloaddition of ethyl 4-chloro-2-oxobut-3-ynoate to the 1,2-disubstituted alkenes was shown to be effectively catalyzed with stannic chloride.     

4-甲基-苯磺酸-2-氧-2-[3-(5-芳基-[1,3,4]噁二唑-2-基)-硫脲]-乙基酯的合成及生物活性研究

合成了12个未见文献报道的4-甲基-苯磺酸2-氧-2-[3-(5-芳基-[1,3,4]噁二唑-2-基)-硫脲]-乙基酯, 其结构经元素分析、¹H NMR和IR确证. 初步活性测试结果表明: 部分化合物有较好的杀菌活性.