Ⅳ.环己基膦酰二氯与高碳醇的醇解反应

环己基膦酰二氯在吡啶存在下与计算量高碳醇进行醇解反应,馏出物中有环己基膦酰氯-2-乙基己酯存在,水解后得环己基膦酸单-2-乙基己酯,环己胺解后得环己基膦酰环己胺2-乙基己酯.将蒸馏后的残渣水解,得环己基膦酸及环己基膦酸单-2-乙基己酯. 本文叙述一种从烷基膦酰二氯合成高碳醇的烷基膦酸二酯及单酯的简便方法.     

磺酰脲的类Mannich反应研究

研究了对甲苯磺酰脲与取代苯甲醛及亚磷酸二酯的类Mannich反应,用竞争反应的方法对不同胺组分发生类Mannich反应的活性进行了比较.合成了一系列α-对甲苯磺酰脲基磷酸二酯的化合物.产物的结构得到¹HNMR和元素分析的证明.初步生物活性测定结果表明其中某些化合物具有很好的抗烟草花叶病毒活性。     

羟基磺酸、氨基磺酸和磺酰肽的合成

具有四面体结构的磺酸衍生物可用于模拟酯键和酰胺键水解的过渡态，特别是 含有四面体结构磺酰胺键的磺酰肽作为天然肽的硫类似物，广泛用于作为酶抑制剂 以及用来诱导抗体酶的半抗原。综述了羟基磺酸、氨基磺酸和磺酰肽的合成。重点 介绍了消旋的和手性的α－和β－取代的β－氨基磺酸及其酰氯和亚磺酰氯，γ－ 氨基－α，β－不饱和磺酸及其酰氯的合成，以及由它们作为基元分子通过液相和 固相方法来合成α－和β－取代的β－磺酰肽、亚磺酰肽及乙烯磺酰肽。     

α-酰氨基烃基膦酸二乙酯的合成及其分子结构的测定

氨基膦酸是继氨基酸、氨基磺酸后在生物体中发现的第三类氨基酸,它在生物体中的分布、代谢和功能正在进一步研究中。目前人们正积极开展合成各种天然氨基酸的磷类似物——α-氨基烃基膦酸的肽,且巴发现这类合成肽具有重要的生理活性。在膦肽合成中,α-酰     

多肽酰肼连接法合成环四肽

环四肽在药物研发中具有重要的潜在应用价值, 然而目前尚缺乏高效率合成环四肽的方法. 我们发展了以N端为半胱氨酸的四肽酰肼为原料的分子内环化方法, 合成了全L型氨基酸组成的环四肽. 该方法通过形成13元环的内硫酯中间体, 再经过S-to-N酰基迁移形成酰胺键, 最后通过脱硫反应, 得到目标环四肽分子.     

N,N'-二(糖基硫代亚脲基)芳基硫代膦酰二胺的合成

N;N'-二(糖基硫代亚脲基)芳基硫代膦酰二胺的合成;糖基异硫氰酸酯;硫代膦酰二肼;生物活性     

手性膦肽核酸单体的合成

肽核酸是一种潜在的反义和反基因药物。膦肽结构的引入克服了肽核酸低水溶性和低细胞膜通透性等缺点,有利于肽核酸的应用。本研究报道手性磷肽核酸单体的合成。还原氨化方法被用于实现N-Boc,N-Fmoc保护的丙氨醛与甘氨膦酸二酯的偶联,BBC-Cl,FEP等缩合剂被用于实现碱基侧链和母链的高效缩合。     

通过基于多肽酰肼的化学连接反应合成高张力环状四肽

刘磊课题组采用其发展的基于多肽酰肼的化学连接反应, 成功合成了一系列高张力环状四肽分子. 多肽酰肼在温和氧化条件下活化为多肽酰基叠氮中间体, 随后与4-巯基苯乙酸形成硫酯, 进而经由分子内天然化学连接反应得到环状四肽. 通过后续的自由基脱硫反应, 可得到连接位点为丙氨酸的产物.     

取代芳氧基酰氧基烃基膦酸（酯）的合成及其构效关系的研究

取代芳氧基酰氧基烃基膦酸（酯）的合成及其构效关系的研究＊汪军ａ刘绪峰ｂ王石泉ｂ汪连生ａ贺红武ｂ（ａ孝感师范高等专科学校化学系孝感４３２１００；ｂ华中师范大学有机合成化学研究所武汉４３００７９）关键词膦酸（酯）除草活性构效关系合成中图分类号Ｏ６２７．５...     

α-氨基烃基膦酸及其衍生物的合成与反应

本文报导合成α-氨基烃基膦酸(1)及其衍生物的新方法与反应。(一)提出用苯甲酰胺(或丙烯酰胺)和醛、亚磷酸三苯酯反应,经水解合成(1);(二)在BF_3·Et_2O催化下用磷酰胺或代磷酰胺、醛和亚磷酸三苯酯或苯基亚磷酸二苯酯反应,生成α-磷胺酰氨基(或硫代磷酰胺基)取代苄膦酸二苯酯或次膦酸苯酯(2)。经选择性脱去氨基保护基生成α-氨基膦酸二苯酯溴代盐(3);(三)二苯氧基氯磷、醛和磷酰胺(或硫代磷酰胺)在 ZnCl_2等路易斯酸存在     

Synthetic Methods of Phosphonopeptides

Phosphonopeptides are phosphorus analogues of peptides and have been widely applied as enzyme inhibitors and antigens to induce catalytic antibodies. Phosphonopeptides generally contain one aminoalkylphosphonic acid residue and include phosphonopeptides with C-terminal aminoalkylphosphonic acids and phosphonopeptides with a phosphonamidate bond. The phosphonamidate bond in the phosphonopeptides is generally formed via phosphonylation with phosphonochloridates, condensation with coupling reagents and enzymes, and phosphinylation followed by oxidation. Pseudo four-component condensation reaction of amides, aldehydes, alkyl dichlorophosphites, and amino/peptide esters is an alternative, convergent, and efficient strategy for synthesis of phosphonopeptides through simultaneous construction of aminoalkylphosphonic acids and formation of the phosphonamidate bond. This review focuses on the synthetic methods of phosphonopeptides containing a phosphonamidate bond.     

Tandem Cross-Coupling/Spirocyclization/Mannich-Type Reactions of 3-(2-Isocyanoethyl)indoles with Diazo Compounds toward Polycyclic Spiroindolines

Tandem reactions of Pd-catalyzed cross-coupling of 3-(2-isocyanoethyl)indoles with diazoacetates and subsequent spirocyclization/Mannich-type reaction have been developed to assemble polycyclic spiroindoline skeletons. Formation of spiroindolenines has been proven as the crucial step for the following Mannich-type cyclization reaction. Accordingly, a novel approach on chiral phosphoric acid catalyzed Mannich-type cyclization toward the formation of diastereomerically and enantiomerically enriched pentacyclic spiroindolines has been established. Moreover, the products of the reaction are versatile building blocks in synthetic chemistry, as demonstrated by the synthesis of the key framework of aspidosperma and kopsia alkaloids.     

Synthesis of phosphinopeptides via the Mannich ligation

Phosphinopeptides are a class of unnatural peptides containing a tetrahedral phosphorus atom and have potential for use as enzyme inhibitors. A series of phosphinopeptides were synthesized via the Mannich-type reaction of aryldichlorophosphines, aldehydes, and N-protected amino amides or peptide amides and subsequent aminolysis with amino esters or peptide esters. The current method named the Mannich ligation is an efficient route to synthesis of phosphinopeptides through convergent condensation.     

Synthesis of 4-benzyl-3-phenylbutenolide natural products

The first total synthesis of eutypoid A and a new synthesis of racemic microperfuranone and gymnoascolide A have been achieved. The key steps in our synthetic strategy involve a Suzuki coupling reaction to install the C3 aryl ring and a Mannich-type reaction for the construction of the 4-benzylbutenolide core.     

Catalytic,asymmetric Mannich-type reactions of N-acylimino esters: reactivity,diastereo- and enantioselectivity,and application to synthesis of N-acylated amino acid derivatives

In the presence of a catalytic amount of Cu(OTf)(2)-chiral diamine 3e complex, N-acylimino esters reacted with silyl enol ethers to afford the corresponding Mannich-type adducts in high yields with high enantioselectivities. A wide variety of silyl enol ethers derived from ketones, as well as esters and thioesters, reacted smoothly. In the reactions of alpha-substituted silyl enol ethers (alpha-methyl or benzyloxy), the desired syn-adducts were obtained in high yields with high diastereo- and enantioselectivities. Several intermediates for the synthesis of biologically important compounds were prepared using this novel catalytic asymmetric Mannich-type reaction, and at the same time, absolute and relative stereochemical assignments were made. In addition, it has been revealed that alkyl vinyl ethers reacted with N-acylimino esters in the presence of a catalytic amount of the Cu(II) catalyst to give the corresponding Mannich-type adducts in high yields with high enantioselectivities. This is the first example of catalytic asymmetric Mannich-type reactions with alkyl vinyl ethers. The reaction mechanism, structure of chiral catalyst-electrophile complexes, and transition states of these catalytic asymmetric reactions were assumed based on X-ray crystallographic analysis of the Cu(II)-chiral amine complex, PM3 calculations, and FT-IR analyses, etc. Finally, (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12, 1), a new inhibitor of ceramide trafficking from endoplasmic reticulum to the site of sphingomyerin (SM) synthesis, has been synthesized efficiently using the present Mannich-type reaction as a key step. The synthesis involved three steps (two-pot), and total yield was 82.9%.     

Lewis base catalyzed Mannich-type reactions between trimethylsilyl enol ethers and aldimines

Lewis base catalyzed Mannich-type reaction between trimethylsilyl enol ethers and N-tosylaldimines is described. Nitrogen anions generated from amides or imides such as lithium benzamide or potassium phthalimide are found to be effective Lewis base catalysts in DMF at room temperature to afford the corresponding beta-amino carbonyl compounds in good to high yields; the oxygen anion generated from carboxylic acids such as lithium acetate was also found to be effective in dry DMF. The above-mentioned lithium acetate-catalyzed Mannich-type reaction between aldimines and various trimethylsilyl (TMS) enol ethers such as silyl ketene acetal proceeded smoothly even in water-containing DMF. Then, Lewis base catalyzed three-component Mannich-type reactions of TMS enol ether, tosylamide, and aromatic aldehyde having electron-withdrawing group such as p-nitrobenzaldehyde were investigated. The reaction proceeded smoothly to afford the corresponding beta-amino ester in good yield. Further, ammonium carboxylates such as tetrabutyl ammonium acetate or tetrabutyl ammonium benzoate were found to be more effective Lewis base catalysts in the above-mentioned Mannich-type reaction. The synthesis proceeded in various solvents at lower temperatures. The reaction between aldimines and TMS enol ethers generated from thioester and various ketones such as propiophenone or cyclohexanone also proceeded smoothly to afford the corresponding beta-amino carbonyl compounds in high yields with good to high anti-selectivities.     

Direct vinylogous Mannich-type reactions via ring opening and rearrangement of vinyloxiranes

[reaction: see text] The first synthetic application of 2-methyl-2-vinyloxirane as a masked dienolate has been successfully demonstrated in the direct vinylogous Mannich-type reaction with an alpha-imino ester as an electrophile. The Mannich adduct was a useful intermediate en route to cis-5-substituted pipecolinic acid ethyl ester under simple hydrogenation conditions.     

Studies toward the total synthesis of gambieric acids, potent antifungal polycyclic ethers: convergent synthesis of the CDEFG-ring system

[reaction: see text] A convergent synthetic route to the CDEFG-ring system of gambieric acids, potent antifungal polycyclic ether marine natural products, has been developed. The present synthesis features convergent union of the CD- and G-rings through esterification, formation of the E-ring as a lactone form, stereoselective allylation to set the C26 stereocenter, and ring-closing metathesis reaction to construct the nine-membered F-ring.     

Synthesis of a “memory tripeptide” (Arg—Glu—Arg,RER) and the Kabachnik—Fields reaction with di- and tripeptides as a method for the synthesis of phosphorus-containing peptide analogs

Methods for the synthesis of potential “twin-drugs” containing fragments of the glutamate receptor antagonist and cognitive function enhancing oligopeptides were developed. The “memory tripeptide” Arg—Glu—Arg (RER) containing the tripeptide sequence of a protein APP_328–330, a gB-amyloid precursor, was synthesized. A method for the synthesis of gA-aminophosphonates with oligopeptides as the amine component of the one-pot three-component Kabachnik—Fields reaction was developed. A method for the synthesis of phosphonopeptides by the introduction of gA-aminophosphonates into the peptide chain was proposed.     

The Preparation and Evaluation of Electron Poor Benzylidene Fischer Carbene Complexes: Studies Toward the Total Synthesis of (+)-Olivin

The continued exploration into the fate of the benzannulation reaction is put forth using the electronic nature of substituents on the aryl ring of benzylidene Fischer carbene complexes as a handle to predict, using σ-para values as a guide, the outcome of the reaction based on the accepted mechanism. The design of this work focuses on evaluation of the synthetic utility of the benzannulation reaction and the means by which this reaction may be improved to be a better synthetic tool in the preparation of complex natural products as this is illustrated in our ongoing total synthesis of (+)-olivin which uses the benzannulation reaction as the key convergent synthetic step. To accomplish these tasks, the preparation of several electron poor benzylidene Fischer carbene complexes was carried out and their reaction with simple alkyne substrates studied. While much is known about the preparation of electron rich benzylidene Fischer carbene complexes, little is known about the preparation of their electron poor counterparts. Thus efforts toward developing useful preparative methods of these elusive targets has also been studied. While the use of both carbon and oxygen based aryl substituents has been explored, to date the preparation of benzylidene carbene complexes containing oxygen based aryl substituents has been exploited to a greater degree since these systems carry more immediate synthetic importance. This is so because the skeletal core of many of the natural products that have been targeted with the benzannulation reaction including (+)-olivin contain a highly oxygenated polycyclic aromatic core. The enhancement in efficiency of the benzannulation reaction using this synthetic methodology is demonstrated by the successful completion of the convergent synthetic step in the total synthesis of (+)-olivin.