RESUMO
Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties including anti-inflammatory, antiviral, and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures but also their promising therapeutic applications as well as the new general synthetic routes developed during the last years.
Assuntos
Produtos Biológicos , IndóisRESUMO
Fluorinated 2-(p-tolylsulfinyl)benzyl carbanions react with allyl and propargyl halides in a highly stereoselective way, providing homoallylic and homopropargylic fluorides, respectively, with high optical purity. Theoretical calculations found transition states for these transformations whose relative stabilities are consistent with the experimentally observed stereoselectivity.
Assuntos
Ânions/química , Compostos de Benzil/química , Fluoretos/química , Hidrocarbonetos Fluorados/química , Hidrocarbonetos Fluorados/síntese química , Pargilina/química , Pargilina/síntese química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Pargilina/análogos & derivados , Teoria Quântica , EstereoisomerismoRESUMO
Asymmetric nucleophilic monofluoroalkylation of a broad range of aldehydes with an α-fluoro-γ-sulfinylbenzyl carbanion takes place with complete control of the facial selectivity at the carbanion and good to high anti-diastereoselectivity to give easily separable mixtures of two optically pure 1,2-fluorohydrin derivatives (up to 24:1 anti/syn). Separation and removal of the p-tolylsulfinyl group with tBuLi provides enantiomerically pure anti-1,2-disubstituted-1,2-fluorohydrins, whereas α-fluorobenzylketones can be obtained by desulfinylation of the mixture followed by pyridinium chlorochromate oxidation (one-pot process).
Assuntos
Aldeídos/química , Compostos de Benzil/química , Flúor/química , Hidrocarbonetos Fluorados/química , Cetonas/química , Sulfóxidos/química , Estrutura Molecular , EstereoisomerismoRESUMO
Enantiomerically pure syn-1,2-diaryl-1,2-sulfanylamine derivatives can be obtained in a completely stereoselective manner by reaction of the benzylcarbanion Li-(S)-1 with N-phenyl (or PMP)-arylidene aldimines and further desulfinylation with t-BuLi. Theoretical studies at the DFT (mPW1PW91) level with the CPCM model, by using the Gaussian09 program, provide a good explanation for the stereochemical results.
Assuntos
Aminas/síntese química , Compostos de Sulfidrila/síntese química , Aminas/química , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular , Teoria Quântica , Estereoisomerismo , Compostos de Sulfidrila/químicaRESUMO
The preparation of a stabilized monofluorobenzyl carbanion by means of a remote homochiral sulfinyl group and its completely stereoselective reactions with N-p-tolylsulfinylimines are described. The use of these reactions followed by the simultaneous removal of both chiral auxiliaries with tBuLi, which occurs without epimerization at the benzylic position, provides the quickest entry to enantiomerically pure ß-fluorinated ß-phenylethylamines.
Assuntos
Ânions/química , Compostos de Benzil/química , Iminas/química , Fenetilaminas/síntese química , Halogenação , Conformação Molecular , Fenetilaminas/química , EstereoisomerismoRESUMO
Aziridination of (R)-N-sulfinylaldimines (aryl, heteroaryl and alkenyl derivatives) with 2-(p-tolyl sulfinyl)benzyl iodide in the presence of sodium hexamethyl disilazide takes place with almost complete control of the stereoselectivity (facial and anti/syn) and with very high yields affording optically pure N-sulfinyl trans-2,3-disubstituted aziridines 7. Simultaneous removal of both C- and N-p-tolylsulfinyl groups with tBuLi provides the corresponding trans-NH aziridines 8 without affecting their optical purity. Some experimental results suggest these processes evolve through benzyl halocarbenoids as intermediates, whereas theoretical calculations support the formation of benzyl carbanions. These results have served for revising the mechanistic aspects of the reactions of substituted 2-p-tolylsulfinyl benzylcarbanions with electrophiles.
RESUMO
(R)-N-sulfinylimine and (S)-N-sulfinylimine react with the ylide derived from (S)-dimethyl-[2-(p-toluenesulfinyl)phenyl]sulfonium salt, affording trans-2,3-disubstituted aziridines. A complete trans selectivity in low facial diastereoselectivity is observed when the configuration at the sulfur atoms of the reagents is the same. Otherwise, when their configurations are different, the reaction evolved with total facial diastereoselectivity and the cis/trans ratio ranged between 1/4.2 and 1/9. Theoretical calculations indicate the reaction proceeds mainly by evolution of a planar free carbanion. The relative stability of the transition states predicts a trans/cis ratio that is in excellent agreement with the experimental results.
Assuntos
Aziridinas/síntese química , Ânions , Iminas/química , EstereoisomerismoRESUMO
(R)- and (S)-N-sulfinylketimines react with the ortho-sulfinyl benzyl carbanion derived from (S)-1 affording epimeric mixtures at the benzylic carbon of alpha,alpha-dibranched beta-sulfanyl amines. The N-sulfinyl group completely controls the configuration at the quaternary carbon bonded to the nitrogen, whereas the C-sulfinyl group is responsible for the level of asymmetric induction. High stereoselectivity can be achieved when the configuration at the sulfur atoms of the reagents are opposite (matched pair). After a two-step desulfinylation process, this reaction provides a procedure for synthesizing diastereomerically pure syn-1,2-sulfanyl amines containing a chiral quaternary carbon adjacent to nitrogen.
Assuntos
Aminas/síntese química , Iminas/química , Ácidos Sulfênicos/química , Aminas/química , Espectroscopia de Ressonância Magnética , Teoria Quântica , Estereoisomerismo , Especificidade por SubstratoRESUMO
Alkylidenation of arylmethyl, dialkyl, and cyclic ketones with 2-( p-toluenesulfinyl)benzyl iodide in the presence of NaN(SiMe3)2 takes place with a high or complete control of the facial selectivity at the carbonyl group (up to 98% de) and the carbanion (>98% de), respectively, yielding mixtures of only two optically pure trisubstituted epoxides ( E/Z ratio ranges between 2:1 and >50:1). Removal of the p-tolylsulfinyl group with t-BuLi provides the corresponding (E)-3-phenyl-2,2-disubstituted epoxides without affecting their optical purity.
RESUMO
Reactions of (S)-alpha-(methylthio)-2-(p-tolylsulfinyl)benzyl carbanion with different carbonyl compounds proceeds with complete control of the configuration at the benzylic position. Aldehydes yield easily separable mixtures of beta-hydroxy sulfides, epimers at the hydroxylic carbon, where the stereoselectivity depends on steric factors (from 20% to >98% de).
Assuntos
Sulfetos/síntese química , Sulfóxidos/química , Derivados de Benzeno/química , Carbonatos/química , Modelos Químicos , Estereoisomerismo , Compostos de Sulfidrila/química , Compostos de Sulfônio/químicaRESUMO
[reaction: see text] The reactions of the lithium (S)-alpha-(methylthio)-2-(p-toluenesulfinyl)benzyl carbanion with (S)-N-p-tolylsulfinyl aldimines evolve in a completely stereoselective manner providing a one-step synthesis of enantiomerically pure anti-1,2-disubstituted 1,2-amino sulfide derivatives.
RESUMO
Reactions of 2-(arylsulfinyl)-1,4-benzoquinones 1a-c with N-(tert-butoxycarbonyl)-2-(tert-butyldimethylsiloxy)pyrrole 2 have been studied under different catalytic conditions. Under BF(3).OEt(2) catalysis, reactions were completely stereoselective leading to the Michael-type adducts 3, whereas in the presence of SnCl(4) diastereomeric mixtures of the pyrrolo[3,2-b]benzofuranes 5 and 6 were obtained. The latter products result from a tandem process involving the Michael reaction followed by an intramolecular cyclization of the intermediates 3 and 4, the first step being hardly stereoselective. Reactions catalyzed by Eu(fod)(3) evolved in a highly stereoselective manner yielding the products 3 or 5 depending on the electronic density of the arylsulfinyl group.