A Tripeptide Approach to the Solid-Phase Synthesis of Peptide Thioacids and N-Glycopeptides

A general and robust method for the incorporation of aspartates with a thioacid side chain into peptides has been developed. Pseudoproline tripeptides served as building blocks for the efficient fluorenylmethyloxycarbonyl (Fmoc) solid-phase synthesis of thioacid-containing peptides. These peptides were readily converted to complex N-glycopeptides by using a fast and chemoselective one-pot deprotection/ligation procedure. Furthermore, a novel side reaction that can lead to site-selective peptide cleavage using thioacids (CUT) was discovered and studied in detail.     

Cascade Syntheses Routes to the Centrocountins

Cascade and domino reactions that proceed through multiple steps in one pot and include multiple bond formations are promising methods for the rapid and efficient generation of complex molecular architectures, including the scaffolds of classes of complex natural product. We describe the development of various one‐pot cascade reaction sequences to yield centrocountins, which are tetracyclic indole derivatives with the basic scaffold of numerous polycyclic alkaloids. The mechanistic investigation of a sequence employing readily available alkynes and 3‐formylchromones as starting materials provided evidence that this one‐pot synthesis proceeds through at least twelve consecutive transformations and includes at least nine different chemical reactions, making it the longest cascade reaction sequence known to date. We describe the scope and limitations of the cascade synthesis approaches and the development of an enantioselectively catalyzed centrocountin synthesis.     

全保护RGD三肽的合成方法研究

以两条路线、多种偶联试剂(DCC，EDCI，CDI，EEDQ)合成了全保护三肽Arg- Gly-Asp(RGD)．Boc-Arg(Tos)-OH经上述偶联剂短时活化，于合适条件下与Ts0H- G1y-OBzl缩合，均获得良好收率(43％-97％)．经Pd(OH)2／H2还原得到的Boc-Arg (Tos)-G1y-0H于22-27℃与HCl·Asp(OcHex)-OBzl偶联得到全保护三肽Boc-Arg (Tos)-Gly-Asp(OcHex)-OBzl(TM)，反应收率分别为76．4％(DCC／HOSu)，64．7％ -78．3％(DCC／HOBt)，66．7％-77．9％(EDCI／HOBt)．Boc-Gly-OH和HCl·Asp- (OcHex)-OBzl经DCC／HOBt或CDI活化，可得到碳端二肽Boc-Gly-Asp(OcHex)-OBzl (收率分别为81．2％，89．5％)，该二肽脱Boc后与Boc-Asp(Tos)-OH反应，经DCC ／HOBt，EDCI／HOBt，CDI，DCC／HOSu活化，均可生成目标分子TM，其反应收率分 别为40．4％，73．8％，67．8％，84．4％．     

Totally Synthetic Routes to the Higher Monosaccharides

The evolution of a strategy to synthesize the title compounds is described. Three principal developments allowed realization of this goal: (1) the attainment of high margins of diastereofacial selectivity and regioselectivity in the construction of pyranoid systems via the Lewis acid-catalyzed cyclocondensation reaction of activated dienes and aldehydes; (2) the exploitation of stereoselective reactions for functionalization of the pyranoid matrix; and (3) the discovery of stereoselective reactions for extending the chiral biases of pyranoid systems to newly emerging stereogenic centers on side chains. The coordination of these components in the synthesis of target systems of high biological interest is described.     

New Routes to Oxindole Derivatives

Summary. A new, practical synthesis of the antirheumatic oxindole derivative, tenidap, has been elaborated. The new approach has initiated studies on the mechanism of the acylation reactions of oxindoles. Methods have been developed for the synthesis of 1-[alkoxy(or aryloxy)carbonyl]- and 1,3-di[alkoxy(or aryloxy)carbonyl]oxindoles starting from oxindoles. The route designed for tenidap has provided a facile access to several analogues, too.On another front, new reaction conditions are described, which turn Wenkerts synthesis of 3-alkyloxindoles (by Raney nickel induced alkylation of oxindoles with alcohols) into a highly efficient synthetic tool. The method has been extended to the synthesis of 3-alkyloxindoles from isatins and to the preparation of 3-(-hydroxyalkyl)oxindoles from oxindoles and isatins.     

Synthetic Routes to 3-Pyrrolidinol

Short, convenient routes to 3-pyrrolidinol are described.     

New Routes to Fused Isoquinolines

Treatment of 6,7‐diethoxy‐3,4‐dihydroisoquinoline ( 8 ) and its 1‐methyl derivative 12 with hydrazonoyl halides 10 in the presence of Et₃N in THF under reflux afforded the corresponding 5,6‐dihydro‐1,2,4‐triazolo[3,4‐a]isoquinolines 11 and 13 , respectively, in high yield (Schemes 2 and 3). The products are formed via regioselective 1,3‐dipolar cycloaddition of the intermediate nitrilimines 9 with the isoquinoline C=N bond. Reaction of 6,7‐diethoxy‐3,4‐dihydroisoquinoline‐1‐acetonitrile ( 4a ) with ethyl α‐cyanocinnamates 15 in the presence of piperidine in refluxing MeCN yielded benzo[a]quinolizin‐4‐ones 16 (Scheme 4). Under the same conditions, 12 and arylidene malononitriles 19 reacted to give benzo[a]quinolizin‐4‐imines 20 (Scheme 5). Instead of 15 and 19 , mixtures of an aromatic aldehyde, and ethyl cyanoacetate or malononitrile, respectively, can be used in a one‐pot reaction.     

Controversy of Peptide Cyclization from Tripeptide

The present investigation reports an attempt to synthesize naturally occurring α-cyclic tripeptide cyclo(Gly-l-Pro-l-Glu) 1, [cyclo(GPE)], previously isolated from the Ruegeria strain of bacteria with marine sponge Suberites domuncula. Three linear precursors, Boc-GPE(OBn)₂, Boc-PE(OBn)G and Boc-E(OBn)GP, were synthesized using a solution phase peptide coupling protocol. Although cyclo(GPE) 1 was our original target, all precursors were dimerized and cyclized at 0 °C with high dilution to form corresponding α-cyclic hexapeptide, cyclo(GPE(OBn))₂ 7, which was then converted to cyclic hexapeptide cyclo(GPE)₂ 2. Cyclization at higher temperature induced racemization and gave cyclic tripeptide cyclo(GP_DE(OBn)) 9. Structure characteristics of the newly synthesized cyclopeptides were determined using ¹H-NMR, ¹³C-NMR and high-resolution mass spectrometry. The chemical shift values of carbonyls of 2 and 7 are larger than 170 ppm, indicating the formation of a cyclic hexapeptide.     

New Routes to Oxindole Derivatives

A new, practical synthesis of the antirheumatic oxindole derivative, tenidap, has been elaborated. The new approach has initiated studies on the mechanism of the acylation reactions of oxindoles. Methods have been developed for the synthesis of 1-[alkoxy(or aryloxy)carbonyl]- and 1,3-di[alkoxy(or aryloxy)carbonyl]oxindoles starting from oxindoles. The route designed for tenidap has provided a facile access to several analogues, too.On another front, new reaction conditions are described, which turn Wenkerts synthesis of 3-alkyloxindoles (by Raney nickel induced alkylation of oxindoles with alcohols) into a highly efficient synthetic tool. The method has been extended to the synthesis of 3-alkyloxindoles from isatins and to the preparation of 3-(-hydroxyalkyl)oxindoles from oxindoles and isatins.     

New Routes to Multicomponent Oxide Glasses

Multicomponent oxide glasses can be produced not only by melting methods but also by hydrolysis and condensation of alkoxide complexes with several metals. This requires temperatures only up to the transformation range of the glass in question, usually 500–600 °C. The process does not pass through the molten phase. It is possible to obtain glasses or polycrystalline substances, depending on the composition. The method is particularly suitable for the production of thin, transparent multicomponent oxide layers of almost any composition on substrates. Some of these layers provide protection against climatic attack or against oxidation.     

Enzymatic Synthesis of a CCK-8 Tripeptide Derivative

The enzymatic synthesis of CCK-8 tripeptide derivative Phae-Met-Asp(OMe)-Phe-NH2 is reported.Starting with Phac-Met-OCam,we have successfully synthesized the target tripeptide with three free or immobilized enzymes, α-chymotrypsin,papain and thermolysin in reasonable yields.The key steps in this synthesis were the coupling of Phac-Met-OCam and H-Asp(OMe)2 to from Met-Asp peptide bond catalyzed by α-chymotrypsin and the selective hydrolysis of α-ester of Phac-met-Asp(OMe)2 catalyzed by papain.     

Routes to regioselective deuteriation of heteroaromatic compounds

A systematic approach to the deuteriation of polypyridyl type ligands is reported. A range of isotopologues of heteroaromatic compounds containing pyrazyl, pyridyl, 1,2,4-triazole, thienyl, methyl, and phenyl moieties, have been prepared in a cost-effective manner, using a range of methods based on subcritical aqueous media. Selectively and fully deuteriated ligands are characterized by mass spectrometry and(1)H, (2)D, and (13)C NMR spectroscopy. The application of deuteriation to supramolecular chemistry is discussed.     

Synthetic Routes to Chiral 3-Pyrrolidinols

Short conyenient syntheses of chiral 3-pyrrolidinols and reloted compounds are described.     

Precursor Routes to Semiconductor Quantum Dots

Abstract

Quantum Dots are unique for two very important reasons both of which can potentially be commercially exploited: ? The electronic and optical properties of Quantum Dots are dependent on the particle size.

? As the Quantum Dot nanoparticle becomes smaller the ratio of the number of surface atoms to those in the interior increase. For example in very small particles greater than a third of all atoms reside on the surface. Such a high surface area is useful for catalysis.

The solutions to the right all contain the same semiconductor material (cadmium selenide, CdSe) but are different colours because unlike the bulk material, which is black, we have controlled the size and therefore the electronic and optical properties (colour) of the Quantum Dots. This property alone can be exploited for the use in a number of technologies such as security tagging and biological probes.

These small particles are one of the inventions spearheading a drive to control of materials with dimensions of the order of nanometres. The potential of the area of nanotechnology as being opened up by interactions between molecular biologists, chemists physisists and almost every type of engineer will be discussed. Applications of such technologies will range from computer chips through display screens to security printing. These new technologies will impact on all of our daily lives. Nanotechnology is attracting attention from all quarters from academia, venture capitalists to the general public. This lecture will explain why the area is both so topical and important.