Carlos Kleber Z. Andrade

3-Arylamino and 3-Alkoxy-nor-β-lapachone Derivatives: Synthesis and Cytotoxicity against Cancer Cell Lines

Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimethoxy substituted naphthoquinones showed the best cytoxicity profile, while the ortho-nitro and the 2,4-dimethoxy substituted ones were more selective than doxorubicin and similar to the precursor lapachones, thus emerging as promising new lead compounds in anticancer drug development.

Novel Supramolecular Palladium Catalyst for the Asymmetric Reduction of Imines in Aqueous Media

A novel approach to the asymmetric reduction of dihydro-beta-carboline derivatives to the corresponding tetrahydro-beta-carbolines is described based on the supramolecular lyophilized complex formed from beta-cyclodextrin/imines as an enzyme mimetic and palladium hydride as the reducing agent. The methodology allowed us to develop a short and efficient preparation of (R)-harmicine and (R)-deplancheine alkaloids in high overall yields and ee of 89 and 90%, respectively.

Niobium(V) chloride-mediated allylation of aldehydes. Scope and stereoselectivity

Abstract Niobium chloride promoted the addition of allylstannanes to aromatic and aliphatic aldehydes. Excellent syn diastereoselectivity was obtained in the addition of E -cinnamylstannane to benzaldehyde (49:1). In the addition of allylstannane to racemic 2-phenylpropionaldehyde, syn diastereoselection (Cram– anti -Cram=3:1) was observed. The same level of diastereoselection was achieved in the reaction between crotylstannane and benzaldehyde.

Fast and efficient microwave-assisted synthesis of functionalized peptoids via Ugi reactions.

A wide range of N-alkylglycines (peptoids) can be efficiently prepared via Ugi reactions using microwave irradiations. The results confirm the versatility and efficiency of the methodology for the preparation of functionalized peptoids. The products can be used in consecutive Ugi reactions to yield cyclic peptoids of potential biological interest.

Bijvoet in solution reveals unexpected stereoselectivity in a Michael addition.

The absolute configuration of small crystallizable molecules can be determined with anomalous X-ray diffraction as shown by Bijvoet in 1951. For the majority of compounds that can neither be crystallized nor easily be converted into crystallizable derivatives, stereocontrolled organic synthesis is still required to establish their absolute configuration. In this contribution, a new fundamental methodology for resolving the absolute configuration will be presented that does not require crystallization. With residual dipolar coupling enhanced NMR spectroscopy, ensembles of a limited number of structures are created reflecting the correct conformations and relative configuration. Subsequently, from these ensembles, optical rotation dispersion (ORD) spectra are predicted by DFT calculations and compared to experimental results. The combination of these two steps reveals the absolute configuration of a flexible molecule in solution, which is a big challenge to chiroptical methods and DFT in the absence of NMR spectroscopy. Here the absolute stereochemistry of the product of a new Michael addition, synthesized via a niobium(V) chiral enolate, will be elucidated by using the new methodology.

Allylation of aldimines promoted by NbCl5

Niobium chloride promoted the addition of allylstannanes to aromatic aldimines. Excellent syn diastereoselectivity was obtained in the addition of crotylstannane to N-benzylideneaniline (46:1).

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids.

Summary The synthesis of six cyclic depsipeptoids inspired by the natural depsipeptide sansalvamide A is described. An efficient and fast synthetic strategy was developed using a combination of consecutive isocyanide-based multicomponent reactions (Ugi and Passerini reactions). This methodology can be used to access a variety of cyclic oligodepsipeptoids.

Biological and structure-activity evaluation of chalcone derivatives against bacteria and fungi

O presente trabalho descreve as atividades antibacterianas e antifungicas de diversas chalconas obtidas diretamente atraves da condensacao aldolica tipo Claisen-Schmidt das quais se determinou a concentracao inibitoria minima frente a diferentes microrganismos (bacterias Gram-positivas e Gram-negativas e fungos). Estruturas no estado solido cristalino de sete chalconas foram determinadas por analise de difracao de raios X (XRD). Estudos quimiometricos foram realizados com intuito de identificar uma potencial relacao entre estrutura e atividade.

Intramolecular ene reactions catalyzed by NbCl5, TaCl5 and InCl3

Pentacloreto de niobio, pentacloreto de tântalo e tricloreto de indio catalisaram eficientemente a ciclizacao do (R)-citronelal a uma mistura de isopulegol e neoisopulegol, em bons rendimentos. Um estudo comparativo foi realizado demonstrando que NbCl5 e o acido de Lewis mais ativo enquanto que InCl3 e o mais seletivo. A seletividade das reacoes variou de acordo com o acido de Lewis utilizado e o solvente. NbCl5 e TaCl5 mostraram ausencia de seletividade enquanto que o InCl3 apresentou seletividade moderada em favor do isopulegol. A reacao ene de um 1,7-dieno tambem foi investigada. Neste caso, todos os acidos de Lewis testados apresentaram excelente seletividade.

Computational approach for the design of AP1867 analogs: aiming at new synthetic routes for potential immunosuppressant agents.

Abstract Molecular modelling and synthetic arguments are valuable tools for the design of potential immunosuppressant agents. In this paper, eight proline-based compounds related to the AP1867 structure are studied and at least one of them is found to be a structurally good candidate for the inhibition of FKBP protein. Theoretical calculations were carried out to locate the most energetically favorable chemical substituent group relative to a core skeleton group on interaction with the FKBP binding cavity. Connolly accessible surface calculations have complemented the molecular mechanics and dynamics approaches. Calculated results were also analyzed on the basis of hydrogen bond interactions, relative energies of interaction, root-mean square deviations of amino acid residues of the crystallized protein, and orientation of the substituent groups within the active site. The results show a significant reduction in the relative interaction energies and very good shape complementarities between our final analog compound and the FKBP binding pocket.