Resumo em inglês This work describes the cyclization of lapachol (1) induced by thallium triacetate (TTA) and thallium trinitrate (TTN) in several solvents using magnetic stirring and under microwave irradiation. alpha-Xyloidone (2) - dehydro-alpha-lapachone - was obtained as the main product in these reactions in 20 75% yield. However, rhinacanthin-A (4) was isolated as main product in a 40% yield, using TTA and acetic anhydride:water (1:1) as solvent, and dehydro-iso-alpha-lapachone (3) (mais) in 21% yield, using TTA and dichloromethane as solvent. The reaction time decreased drastically under microwave conditions, but the yields of these reactions were not the expected.
Resumo em português Muitos fármacos estão associados a vários efeitos adversos e limitada biodisponibilidade. A resolução destes problemas continua sendo um alvo importante para a comunidade científica. O desenvolvimento de pró-fármacos que conduzam a uma liberação controlada in vivo é um caminho atrativo para resolver estes problemas. Um pró-fármaco clássico é molécula inativa, em que o princípio ativo é ligado covalentemente a uma unidade transportadora, de modo que o fá (mais) rmaco pode ser liberado através de uma reação química ou enzimática. Um sistema novo e interessante de pró-fármaco, que tem sido apresentado para fármacos possuidores de grupos amino, álcool e tiol, é aquele no qual o princípio ativo é liberado através de uma ciclização intramolecular. Neste caso, o processo de ciclização, dependendo da cadeia da unidade transportadora e do próprio fármaco, pode controlar a velocidade de liberação do princípio ativo. Desta forma, este trabalho apresenta uma revisão do desenvolvimento de pró-fármacos baseados na liberação do princípio ativo através de uma ciclização intramolecular. Resumo em inglês Many drugs used for the treatment of common diseases are associated with various adverse effects and limited bioavailability. The suppression of such problems continues to be a very important target for scientists. The development of prodrugs for controlled release in vivo is an attractive way to overcome these problems. Classical in prodrug is an inactive molecule which the parent drug is covalently bonded to a carrier unit, and which can liberate the drug through chemic (mais) al or enzymatic pathways. A new and interesting prodrug system for amine, alcohol, and thiol drugs takes advantage of several easy intramolecular cyclization reactions. So, the cyclization process can control the release rate of the parent drug. In this paper is a review about the prodrug strategies based on intramolecular cyclization reactions is presented.
A reação de ciclização de prins: uma estratégia eficiente para síntese estereosseletiva de anéis tetraidropirânicos substituídos/ The prins cyclization reaction: an efficient stractegy for the stereoselective synthesis of substituted tetrahydropyran rings
Resumo em inglês The Prins cyclization reaction has significantly advanced in the last years as demonstrated by a number of applications described in the literature. The objective of this report is to introduce this powerful synthetic methodology to the undergraduate and graduated student, since it is rarely presented in an organic synthesis formal course. This reaction is, in some cases, the methodology of choice for the preparation of natural products or drugs that present the tetrahydr (mais) opyrane moiety in their structures. In this report we show some aspects of this reaction, including mechanism, scope and limitations.
Síntese de aliloxi-orto-iodobenzamida derivada de d-glicose e reação de ciclização radicalar mediada por hidreto de tri-n-butilestanho/ Synthesis of allyloxy-ortho-iodobenzamide derivative from d-glucose and tri-n-butyltin hydride mediated radical cyclization reaction
Resumo em inglês Methyl 6-O-allyl-2,3-di-O-benzyl-4-deoxy-4-(2 -iodobenzoylamine)-alpha-D-glucopyranoside was synthesized in nine conventional steps from methyl alpha-D-glucopyranoside. Its Bu3SnH-mediated aryl radical cyclization provided a benzomacrolactam, resulting from 11-endo aryl radical cyclization and the reduced uncyclized product methyl 6-O-allyl-4-benzoylamine-2,3-di-O-benzyl-4-deoxy- alpha-D-glucopyranoside. The structures of the three new products were supported by ¹H and 13C NMR spectroscopy and DEPT, COSY and HMQC experiments.
Resumo em português O óleo essencial das folhas de Myrcianthes gigantea (Myrtaceae), coletadas no Rio Grande do Sul, foi obtido por hidrodestilação em Clevenger e analisado por CG/detector de ionização de chamas e CG/EM. Trinta e seis compostos foram identificados, totalizando 90,1% do conteúdo do óleo. A composição do óleo demonstrou predominância de sesquiterpenos cíclicos, principalmente da via de ciclização do germacrano, apresentando espatulenol (28,8%) e seu isômero, iso (mais) -espatulenol (9,5%), como principais constituintes. A composição do óleo das folhas de M. cisplatensis e M. pungens, coletadas na mesma região, também foi analisada e comparada com estudos prévios reportados para estas espécies coletadas em outros países da América da Sul. O óleo essencial de M. cisplatensis apresentou um alto conteúdo de monoterpenos (56,3%), especialmente das séries pinano e p-mentano, com três compostos majoritários: 1,8-cineol (29,8%), limoneno (10,9%) e a-pineno (8,9%), sendo similar ao reportado. Para o óleo de M. pungens 36 compostos foram identificados, porém sem predomínio majoritário, onde b-cariofileno (10,1%), foi o principal deles. O óleo desta espécie difere do relatado para exemplares coletados na Argentina, rico em monoterpenos, sugerindo uma possível ocorrência de quimiotipos. Resumo em inglês The essential oil of Myrcianthes gigantea (Myrtaceae) leaves, which were collected in Rio Grande do Sul (Southern Brazil), was obtained by hydrodistillation in a Clevenger apparatus. The chemical investigation was performed by GC-FID and GC-MS. Thirty-six compounds were identified accounting for 90.1% of the oil content. The analyzed species was rich in cyclic sesquiterpenes, mainly those from the germecrane cyclization pathway, among them spathulenol (28.8%) and its isom (mais) er, iso-spathulenol (9.5%). Leaves of M. cisplatensis and M. pungens were also collected in the same region and the analysis of the oil composition was compared with those previously reported for collections from other countries in South America. M. cisplatensis oil showed a high content of monoterpenes (56.3%), specially from the p-mentane and pinane groups, with three major compounds: 1,8-cineole (29.8%), limonene (10.9%) and a-pinene (8.9%). These findings are in agreement with those reported previously. For M. pungens, thirty-six compounds were identified without a predominant component. b-caryophyllene (10.1%), with caryophyllane skeleton, was the main substance for this sample. For this species the oil composition was quite different from those related for two exemplars collected in Argentina, in which both oil were rich in monoterpenes. This result suggests the occurrence of chemotypes.
Resumo em inglês Essential oils from M. richardiana, M. arborescens, M. selloi, M. oligantha, M. rostrata, M. lajeana, M. obtecta, M. pubipetala and M. hatschbachii were obtained by hydrodistillation and analyzed by GC and GC/MS. Sixty-seven compounds have been identified ranging from 90-99% of the oil contents. All analyzed species were rich in cyclic sesquiterpenes (66-99%), mainly those from the cadinane, caryophyllane and germacrane cyclization pathway, among them b-caryophyllene, ger (mais) macrene D, bicyclogermacrene, d-cadinene, spathulenol, caryophyllene oxide, globulol and a-cadinol. The acyclic sesquiterpene series was well represented by M. lajeana (32.1%), with 25,3% of (E)-nerolidyl acetate.
Síntese de β-cetoésteres cíclicos: novo procedimento para ciclizações de Dieckmann empregando ALCL3 e trietilamina/ Synthesis of β-keto esters: new easy procedure for dieckmann cyclization employing aluminum chloride and triethylamine
Resumo em inglês In this communication we describe a new methodology to Dieckmann cyclization of diethyl adipate (1) and diethyl pimelate (3) applying "push-pull" strategy using anhydrous aluminium trichloride and triethylamine in dichloromethane at room temperature. This method is very efficient, simple, safe and reproducible, giving the corresponding cyclic β-keto ester derivatives in 84% and 71% yield, respectively.
Resumo em inglês The indan ring system is present in several compounds with important pharmacological properties. In this account recent examples of selected methods (Friedel-Crafts acylation, cycloaddition reactions, ring contraction, cyclization and resolution) for the synthesis of indans are discussed.
Síntese de 2-iodobenzamidas e 3-(iodoacetamido)benzamidas ligadas à D-galactose e suas reações de carbociclização radicalar mediadas por hidreto de tri-n-butilestanho/ Synthesis of 2-iodobenzamides and 3-(iodoacetamido)benzamides linked to D-galactose and their tri-n-butyltin hydride-mediated radical carbocyclization reactions
Resumo em inglês Starting from methyl 6-O-allyl-4-azido-2,3-di-O-benzyl-4-deoxy-α-D-galactopyranoside, four new derivatives containing 2-iodobenzamido and 3-(iodoacetamido)benzamido groups were synthesized. These four compounds were submitted to tri-n-butyltin hydride mediated radical cyclization reactions, resulting in two macrolactams from 11- and 15-endo aryl radical cyclization. The corresponding four hydrogenolysis products were also obtained. The structures of the new compounds were elucidated by ¹H and 13C NMR spectroscopy, DEPT, COSY, HMQC and HMBC experiments.
Síntese de 1-indanonas através da reação de acilação de Friedel-Crafts intramolecular utilizando NbCl5 como ácido de Lewis/ Synthesis of 1-indanones through the intramolecular Friedel-Crafts acylation reaction using NbCl5 as Lewis acid
Resumo em inglês The intramolecular Friedel-Crafts acylation reaction of 3-arylpropanoic acids to give 1-indanones can be effected in good yields under mild conditions (room temperature) by using niobium pentachloride. Our results indicate that NbCl5 acts both as reagent (to transform carboxylic acids into acyl chlorides) and as catalyst in the Friedel-Crafts cyclization.
Reações de carbociclização radicalar de orto-iodoaliloxibenzoatos derivados de d-glicose e d-galactose e comparação com as reações de seus análogos benzamidas/ Radical carbocyclization reactions of ortho-iodoallyloxybenzoate derivatives of d-glucose and d-galactose and comparison with the reactions of their benzamide analogs
Resumo em inglês Two ortho-iodoallyloxybenzoates, methyl 4-O-allyl-2,3-di-O-benzyl-6-O-(2-iodobenzoyl)- alpha-D-glucopyranoside (3) and methyl 4-O-allyl-2,3-di-O-benzyl-6-O-(2-iodobenzoyl)- alpha-D-galactopyranoside (4) were synthesized in seven conventional steps from methyl alpha-D-glucopyranoside and methyl alpha-D-galactopyranoside, respectively. Bu3SnH-mediated aryl radical cyclization of 3 provided exclusively the hydrogenolysis product 12. The reaction of 4 gave the reduced uncycli (mais) zed product 13 and only traces of 4A, resulting from 11-endo aryl radical cyclization. In previous papers we described that in similar Bu3SnH-mediated radical reaction of ortho-iodoallyloxybenzamides, analogs of 3 and 4, we obtained macrolactams resulting from 11-endo cyclization. An hypothesis to explain the differences is presented. It was assumed that in the aryl radical formed from iodobenzamides there is a suitable conformation to cyclization, which is stabilized by an intramolecular hydrogen bond.
Peptídeos cíclicos de biomassa vegetal: características, diversidade, biossíntese e atividades biológicas/ Cyclic peptide from plant biomass: chemical features and diversity, biosynthesis and biological activities
Resumo em inglês Natural peptides are outstanding as the most promising macromolecules in the search for new drugs, especially those of cyclic nature. The higher plants revealed a very peculiar composition of their cyclic peptides, which distinguish themselves by a "head-to-tail" cyclization. It is possible to define two groups of cyclic peptides from plant biomass. Those called in this review as Eucyclopeptides formed by 2-12 amino acid, and Cyclotides considered as circular polypeptides (mais) , composed of 29-37 amino acid that retain three disulfides bridges in an arrangement known as cyclic cystine knot. Searching for plant peptides should form into a subject for scientific research in the forefront of great importance for bioprospecting natural products macromolecular.
Resumo em inglês Molecules containing the 4-thiazolidinone ring are known to possess a wide range of biological properties including antimicrobial and anti-inflammatory activities among others. These compounds can be synthesized by cyclization reactions involving alpha-haloacetic acid or alpha-mercaptoacetic acid and employed in several chemoselective reactions. Comprehensive reviews have been written on 4-thiazolidinones in 1961 by Brown and in 1980 by Singh et al. In the recent literatu (mais) re, some new synthesis methods for 4-thiazolidinone derivatives and several reactions have been reported. These advances warrant to review the chemical and biological properties of compounds with this important heterocycle employed in synthetic organic chemistry and medicinal chemistry.
Macrolactamas bioativas e síntese de macrociclos por reação de carbociclização radicalar mediada por hidreto de tri-n-butilestanho/ Bioactive macrolactams and synthesis of macrocycles by tri-n-butyltin hydride-mediated radical carbocyclization reaction
Resumo em inglês This review presents natural, semi-synthetic and synthetic bioactive macrolactams and their structure-activity relationships when available. For macrolactams in clinical use the advantages and disadvantages in relation to other drugs are presented, and for synthetic macrolactams the method used in the cyclization is showed. Regarding macrocyclic synthesis by the tri-n-butyltin hydride-mediated radicalar carbocyclization reaction the precursor, the reaction conditions, products and yields, mechanism and cyclization mode are discussed.
Heterociclos 1,2,3-triazólicos: histórico, métodos de preparação, aplicações e atividades farmacológicas/ 1,2,3-triazolic heterocycles: history, preparations, applications and pharmacological activities
Resumo em inglês The 1,2,3-triazole, known since the end of 19th century, is a very widely used heterocyclic system present in many synthetic substances and commercial pharmaceutical compounds. In fact, 1,2,3-triazoles show several applications in many areas especially as medicines against many diseases like cancer, AIDS, Parkinson and Alzheimer. Nowadays there is a large variety of known methods to obtain these heterocyclic compounds comprising mainly three synthetic routes. Nevertheless (mais) , there is no article that gives an objective overview of the synthetic methods for obtaining these kinds of azoheterocycles. This paper presents a brief history of this class of compounds, and a synthetic discussion concerning the main synthetic methods for its preparation, such as cyclization through hydrazones, concerted cycloadditon [2+3] and pseudopericyclic cyclization - and some others of restricted application, but also important. Finally, this paper also provides a brief overview on pharmacological applications of some 1,2,3-triazoles.
Resumo em inglês Irradiation of a,a-dimethylvalerophenone (1) adsorbed on microcrystalline cellulose employing methanol as the solvent shows a Norrish Type II/Type I ratio of 1.0±0.1. In solution, values of 2.3±0.3 in benzene and 8.7±2.0 in terc-butanol were obtained. The cyclization/elimination ratio for the Norrish Type II reaction of 1 shows values of 1.2±0.3 in cellulose, 17.9±2.7 in benzene and 3.2±03 in terc-butanol. When samples of 1/microc (mais) rystalline cellulose were prepared employing n-hexane, the Type II/Type I (29.5±2.9) and the cycl/elim (113.3±12.1) ratios were dramatically modified. These results demonstrate the difference in the behavior of 1 when entrapped in the cellulose chains or adsorbed on the cellulose surface.