Analyzing the n→π* Electronic Transition of Formaldehyde in Water. \ud A Sequential Monte Carlo/Time-Dependent Density Functional Theory

The n→π* absorption transition of formaldehyde in water is analyzed using combined and sequential classical Monte Carlo (MC) simulations and quantum mechanics (QM) calculations. MC simulations generate the liquid solute-solvent structures for subsequent QM calculations. Using time-dependent density functional theory in a localized set of gaussian basis functions (TD-DFT/6-311++G(d,p)) calculations are made on statistically relevant configurations to obtain the average solvatochromic shift. All results presented here use the electrostatic embedding of the solvent. The statistically converged average result obtained of 2300 cm-1 is compared to previous theoretical results available. Analysis is made of the effective dipole moment of the hydrogen-bonded shell and how it could be held responsible for the polarization of the solvent molecules in the outer solvation shells.A transição eletrônica n→π* do formaldeído em água é analisada usando-se um procedimento combinado e seqüencial de Monte Carlo (MC) clássico e mecânica quântica (MQ). MC é usado para gerar configurações do líquido para uso posterior em cálculos de MQ. Usando-se a representação espectral da teoria do funcional da densidade com uma base de funções gaussianas localizadas (TD-DFT/6-311++G(d,p)) cálculos são realizados em configurações estatisticamente descorrelacionadas para se obter o deslocamento solvatocrômico. Todos os resultados são obtidos usando-se uma representação onde o solvente é tratado como um campo eletrostático. O resultado médio obtido de 2300 cm-1 é comparado com resultados teóricos anteriores. Análise é feita do valor do momento de dipolo efetivo da camada associada com as ligações de hidrogênio e como ela pode influenciar as camadas de solvatação mais externas

Synthesis of New Building Blocks: Toward the Analogs of Peptide Nucleic Acids (PNAs)

To obtain new analogs of peptide nucleic acids (PNAs), synthesis of the building block 14 has been achieved. Building block 14 has been derived from the coupling of the isothiocyanate derivative, 12 with 13. Isothiocyanate derivative 12 was obtained from S-aspartic acid derivative 5 in a number of steps.NRC publication: Ye

Combinatorial chemistry

NRC publication: Ye

Remote Asymmetric Induction: Synthesis of C-Linked \u3b1-Galactoserine and Homoserine Derivatives by Electrophilic Amination

A high diastereoselectivity (98%) for electrophilic amination of compound 9 using di-r-butyl azodicarboxyl ester as an electrophile was achieved. A similar reaction with compound 13 having achiral oxazolidinone was studied to examine 1,4-remote asymmetric induction. In the latter, a selectivity of 6.5:1 demonstrated the effect of a-galactosyl moiety, responsible for inducing the induction from the remote siteNRC publication: Ye

Toward high-throughput synthesis of complex natural product-like compounds in the genomics and proteomics age

In the age of high-throughput biology, novel genes and proteins are emerging quickly. the need for developing organic synthesis-derived methods that allow rapid access to polyfunctional, complex natural product-like compounds is growing constantly, largely because these small-molecule-based compounds serve as smart, powerful tools both in understanding the roles and functions of emerging biological targets and in validating their biological responses. Developing asymmetric synthesis-derived organic reactions on solid phase allows the sythesis of complex natural product-like compounds in a high-throughput manner. Solid phase organic sythesis is now commonly utilized in the library synthesis of rather simple compounds (i.e., compounds with no multiple stereogenic centers). With few exceptions, the sythesis of complex natural product-like derivatives is still in its infancy. Some recent efforts made in this area indicate opportunities yet to be explored.NRC publication: Ye

Stereoselective Synthesis of Neo-c-glycopeptide Building Blocks: Towards a Flexible and Control-oriented Design as probes for Carbonhydrate-protein Interactions

Neo-C-glycopeptides (1-4) have been synthesized as building blocks to obtain higher neo-Cglycopeptides as probes for studying carbohydrate-protein interactions. A convergent approach for the synthesis of 4 has been developed, in which two galactose units are attached to a glycine derivative in a stepwise procedure (reductive amination followed by amide coupling) and finally coupling to the protected dipeptide having a free amino group on the side chain.NRC publication: Ye

Carbonylation reactions of iodoarenes with PAMAM dendrimer-palladium catalysts immobilized on silica

Palladium complexes immobilized onto generation 0-3 PAMAM dendrimers supported on silica were used as catalysts for the carbonylation of iodobenzene in methanol to form methyl benzoate. High yields were obtained and the catalyst was recycled 4-5 times without significant loss of activity. The carbonylation reaction was found to be applicable to a variety of iodoarenes regardless of the nature of the substituent.NRC publication: Ye

Part 3. A Novel Stereocontrolled, In Situ, Solution- and Solid-Phase, Aza Michael Approach for High-Throughput Generation of Tetrahydroaminoquinoline-Derived Natural-Product-like Architectures

With the goal of rapidly accessing tetrahydroquinoline-based natural-product-like polycyclic architectures, herein, we report an unprecedented, in situ, stereocontrolled Aza Michael approach in solution and on the solid phase. The mild reaction conditions required to reach the desired target are highly attractive for the use of this method in library generation. To our knowledge, this approach has not been used before, and it opens a novel route leading to a wide variety of tetrahydroquinoline-derived bridged tricyclic derivatives.NRC publication: Ye

Automated, solid-phase synthesis of C-neoglycopeptides : Coupling of glycosyl derivatives to resin-bound peptides

A fully automated solid-phase synthesis of C-neoglycopeptides has been developed using a convergent strategy. In this approach, C-glycoside derivatives (3 and 4) were coupled to resin-bound peptides using a peptide synthesizer. An advantage of the convergent approach is the ability to introduce multiple glycoside units late in the synthesis. The approach presented is highly versatile and efficient and could be used for building C-neoglycopeptide libraries. In our study, neoglycopeptides 5 and 6 were obtained from the coupling of C-glycoside derivatives (3 and 4) to a free amino group of the side chain of short peptides (2, n = 1 and 3). A similar approach was developed for the synthesis of bivalent neoglycopeptides 8 and 9 in an automated manner. The successful syntheses of C-neoglycopeptides 5, 6, 8, and 9 are the first examples of coupling of C-glycosyl carboxyl derivatives to the amino groups of the side chains of resin-bound peptides.NRC publication: Ye

Part 1. Modular Approach to Obtaining Diverse Tetrahydroquinoline-Derived Polycyclic Skeletons for Use in High-Throughput Generation of Natural-Product-like Chemical Probes

A practical synthesis of a tetrahydroaminoquinoline scaffold (12) was developed that used a stereocontrolled aza Michael as the key reaction. Three tetrahydroquinoline alkaloid-like, tricyclic derivatives 16, 18, and 19 with different medium to macrocyclic ring skeletons were obtained, using this scaffold as the starting material, in a modular manner. The macrocyclic compounds with an isolated olefin and an electron-deficient olefin were obtained by ring-closing metathesis approaches. Compounds 16 and 18 are unique and contain bridged 10- and 12-membered functionalized rings. The NMR studies of these compounds revealed interesting information on the conformation of the bicyclic scaffolds that was dependent on the nature and the size of the macrocyclic rings. Finally, this modular methodology, using compound 21 anchored onto the solid support, successfully led to the generation of different macrocyclic derivatives, 23, 25, and 27 in solid-phase synthesis. The solid-phase synthesis approach outlined in this article has the potential to generate tetrahydroquinolinebased tricyclic compounds containing different medium to macrocyclic architectures.NRC publication: Ye