Parallel synthetic methods

The parallel synthetic methods, while being very slow and expensive when compared to the split-mix procedure, have two advantages ... 

As a member of the thiadiazole family, which is a privileged structure for the generation of drug-like libraries, 1,2,4-thiadiazoles have been used as the basic framework for substances of interest in numerous therapeutic areas Recently, we reported the results of a study that led to the development of a solution-phase parallel synthesis of various drug-like 5-amino-1,2,4-thiadiazoles via a three-component nucleophiUc substitution reaction between carbon disulhde, benzamidine, and benzyl chloride, using a key cyclization reaction of a carboxamidine dithiocarbazate induced by TsCl. We also developed a simple and efficient solid-phase parallel synthetic method capable of facilitating the... 

Recent development of combinatorial and parallel synthetic methods combined with high-throughput screening has opened a new chapter in drug discovery research. Additionally, our knowledge of... 

Abstract Many similarities between the chemistry of carbon and phosphorus in low coordination numbers (i.e.,CN=l or 2) have been established. In particular, the parallel between the molecular chemistry of the P=C bond in phosphaalkenes and the C=C bond in olefins has attracted considerable attention. An emerging area in this field involves expanding the analogy between P=C and C=C bonds to polymer science. This review provides a background to this new area by describing the relevant synthetic methods for P=C bond formation and known phosphorus-carbon analogies in molecular chemistry. Recent advances in the addition polymerization of phosphaalkenes and the synthesis and properties of Tx-con-jugated poly(p-phenylenephosphaalkene)s will be described. 

The syntheses and spectroscopic and electrochemical characterization of the rhodium and iridium porphyrin complexes (Por)IVI(R) and (Por)M(R)(L) have been summarized in three review articles.The classical syntheses involve Rh(Por)X with RLi or RMgBr, and [Rh(Por) with RX. In addition, reactions of the rhodium and iridium dimers have led to a wide variety of rhodium a-bonded complexes. For example, Rh(OEP)]2 reacts with benzyl bromide to give benzyl rhodium complexes, and with monosubstituted alkenes and alkynes to give a-alkyl and fT-vinyl products, respectively. More recent synthetic methods are summarized below. Although the development of iridium porphyrin chemistry has lagged behind that of rhodium, there have been few surprises and reactions of [IrfPorih and lr(Por)H parallel those of the rhodium congeners quite closely.Selected structural data for rr-bonded rhodium and iridium porphyrin complexes are collected in Table VI, and several examples are shown in Fig. 7. ... 

Parallel to the search for synthetic methods to make rings of all sizes, kinetic studies have appeared with the aim of providing insight into physical aspects of ring closure. Earlier kinetic work has been reviewed by Salomon (1936a) and Bennett (1941), and more recent work by Illuminati and Mandolini (1981) and Winnik (1981a). 

Catalytic transformations of alkynes have recently led to tremendous developments of synthetic methods with useful applications in the synthesis of natural products and molecular materials. Among them, the selective activations of terminal alkynes and propargylic alcohols via vinylidene- and allenylidene-metal intermediates play an important role, and have opened new catalytic routes toward anti-Markovnikov additions to terminal alkynes, carbocyclizations or propargylations, in parallel to the production of new types of molecular catalysts. 

Many of the examples mentioned have been directly concerned with, or have a consequential importance, to the area of parallel high throughput chemical processing. Any methodology that offers the ability to accelerate the synthesis of large chemical libraries or to access new chemical entities in a clean fashion needs careful consideration. It is certainly true that we have only just begun to comprehend and contemplate the possibilities that the combination of these two powerful technologies could offer. It is therefore hoped that this short chapter will in some way stimulate you, the reader, to have a new outlook on these synthetic methods. 

Wilkinson s (I) discovery that the soluble rhodium(I) phosphine complex, [Rh(PPh3)3Cl], was capable of homogeneous catalytic hydrogenation of olefins immediately set off efforts at modifying the system for asymmetric synthesis. This was made possible by the parallel development of synthetic methods for obtaining chiral tertiary phosphines by Horner (2) and Mislow (3,4, 5). Almost simultaneously, Knowles (6) and Horner (7) published their results on the reduction of atropic acid (6), itaconic acid (6), a-ethylstyrene (7) and a-methoxystyrene (7). Both used chiral methylphenyl-n-propyl-phosphine coordinated to rhodium(I) as the catalyst. The optical yields were modest, ranging from 3 to 15%. 

MATHEY Phosphorus-Carbon Heterocyclic Chemistry The Rise of a New Domain McKILLOP Advanced Problems in Organic Reaction Mechanisms OBRECHT Solid Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries OSBORN Best Synthetic Methods - Carbohydrates PELLETIER Alkaloids Chemical and Biological Perspectives SESSLER WEGHORN Expanded Contracted and Isomeric Porphyrins WONG WHITESIDES Enzymes in Synthetic Organic Chemistry... 

The dispersion of carbon nanotubes in PU matrix can also be affected by the synthetic methods as well as the tensile stress etc. Xiong et al. found that the CNTs in the composites after tensile testing could easily take an ordered orientation along with the tensile direction on the cross-section perpendicular to the pressure direction, whereas the arrangement of the CNTs has not almost changed on the cross-section parallel to the pressure direction (62). The phenomenon that the SWNTs near the film substrate interface are driven to self-organize to a more ordered structure was discovered by Chen et al. (16). 

Acylation of free hydroxyl at C-7 in paclitaxel usually led to the reduction and even loss of cytotoxicity of the derivatives, when steric hindrance of the acyl groups increases. Bhat et al. have used a parallel solution phase synthetic method to construct a 26-membered library of C-7 esters, and concluded that modification at C-7 were detrimental to cytotoxicity against the MCF-7 cell line. Only a few exceptions, including 10-deacetyl-lO-propionyl-7-chloroacetyl... 

The applications of fluorous chemistry in high-throughput or parallel synthesis are many since fluorous reagents and separation techniques can be used in all stages of synthesis and work-up. As a result, fluorous chemistry can today offer a whole parallel synthetic strategy to traditional chemical methods. 

A parallel synthesis method for the synthesis of a dihydropteridine library in five steps was recently published by Zhang. The synthetic route was based on the use of fluorous amino acids, which were prepared from A-Boc-amino acids. The final cyclization was promoted by the use of microwave heating. 

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