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1.
J Org Chem ; 89(16): 11513-11524, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39051980

RESUMEN

N-Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access N-acyl/sulfonyl-α-functionalized THIQs. This method features the use of oxygen (from air) as the green oxidant, high atom and step economy, and decent structural diversity. The synthetic applicability of the method was further demonstrated via the facile construction of valuable bioactive molecules. Mechanistic studies indicated that oxidation with singlet oxygen and the acceptor-less dehydrogenation were involved in the photoredox process.

2.
Org Biomol Chem ; 22(16): 3204-3208, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38563260

RESUMEN

An efficient palladium-catalyzed [2 + 2 + 1] annulation of 3-iodochromones, bridged olefins, and iodomethane is described, affording a range of chromone-containing polycyclic compounds. Additionally, the corresponding deuterated products were smoothly obtained with iodomethane-d3 instead of iodomethane. Moreover, the synthetic utility of this method is further substantiated by gram scale preparation and application to late-stage modification of estrone.

3.
Angew Chem Int Ed Engl ; 63(13): e202318887, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38237082

RESUMEN

Trifluoromethyl cationic carbyne (CF3 C+ :) possessing dual carbene-carbocation behavior emulated as trifluoromethyl metal-carbynoid (CF3 C+ =M) has not been explored yet, and its reaction characteristics are unknown. Herein, a novel α-diazotrifluoroethyl sulfonium salt was prepared and used in Rh-catalyzed three-component [2+1+2] cycloadditions for the first time with commercially available N-fused heteroarenes and nitriles, yielding a series of imidazo[1,5-a] N-heterocycles that are of interest in medicinal chemistry, in which the insertion of trifluoromethyl Rh-carbynoid (CF3 C+ =Rh) into C=N bonds of N-fused heteroarenes was involved. This strategy demonstrates synthetic applications in late-stage modification of pharmaceuticals, construction of CD3 -containing N-heterocycles, gram-scale experiments, and synthesis of phosphodiesterase 10A inhibitor analog. These highly valuable and modifiable imidazo[1,5-a] N-heterocycles exhibit good antitumor activity in vitro, thus demonstrating their potential applications in medicinal chemistry.

4.
J Org Chem ; 88(1): 371-383, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36563325

RESUMEN

A cooperative tertiary amine/palladium-catalyzed sequential reaction process, proceeding via a [4 + 3] cyclization of isatin-derived Morita-Baylis-Hillman Expansion (MBH) carbonates and tert-butyl 2-(hydroxymethyl)allyl carbonates followed by a [1,3]-rearrangement, has been found and developed. A range of structurally diverse spiro[methylene cyclopentane-1,3'-oxindolines] bearing two adjacent ß,γ-acyl quaternary carbon stereocenters, which are difficult to obtain by conventional strategies, were obtained in good yields. Further synthetic utility of this protocol is highlighted by its excellent regio- and stereocontrol as well as the large-scale synthesis and diverse functional transformations of the synthetic compounds. Moreover, the control experiments probably established the plausible mechanism for this sequential [4 + 3] cyclization/[1,3]-rearrangement process.


Asunto(s)
Carbonatos , Paladio , Ciclización , Estructura Molecular , Estereoisomerismo , Catálisis , Aminas
5.
J Org Chem ; 88(5): 3238-3253, 2023 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-36866581

RESUMEN

A practical and efficient electrochemical intramolecular amino- or oxysulfonylation of internal alkenes equipped with pendant nitrogen or oxygen-centered nucleophiles with sodium sulfinate was developed. Under undivided electrolytic cell conditions, a variety of sulfonylated N-heterocycles and O-heterocycles, such as tetrahydrofurans, tetrahydropyrans, oxepanes, tetrahydropyrroles, piperidines, δ-valerolactones, etc., were efficiently prepared from easily accessible unsaturated alcohols, carboxylic acids, and N-tosyl amines without the need for additional metal or exogenous oxidant. The robust electrochemical transformation features excellent redox economy, high diastereoselectivity, and broad substrate specificity, which provide a general and practical access to sulfone-containing heterocycles and would facilitate the related synthetic and biological studies based on this electrosynthesis.

6.
Bioorg Chem ; 138: 106640, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37320911

RESUMEN

Enantiopure ß-nitroalcohols, as an important class of nitro-containing compounds, are essential building blocks in pharmaceutical and organic chemistry, particularly for the synthesis of ß-adrenergic blockers. In this study, we present the successful protein engineering of halohydrin dehalogenase HHDHamb for the enantioselective bio-nitration of various phenyl glycidyl ethers to the corresponding chiral ß-nitroalcohols, using the inexpensive, commercially available, and safer nitrite as a nitrating agent. The chiral (R)- and (S)-1-nitro-3-phenoxypropan-2-ols were synthesized by the several enantiocomplementary HHDHamb variants through the whole-cell biotransformation, which showed good catalytic efficiency (up to 43% isolated yields) and high optical purity (up to >99% ee). In addition, we also demonstrated that the bio-nitration method was able to tolerate the substrate at a high concentration of 1000 mM (150 g/L). Furthermore, representative synthesis of two optically active enantiomers of the ß-adrenergic blocker metoprolol was successfully achieved by utilizing the corresponding chiral ß-nitroalcohols as precursors.


Asunto(s)
Antagonistas Adrenérgicos beta , Éteres Fenílicos , Antagonistas Adrenérgicos beta/química , Biocatálisis , Catálisis , Estereoisomerismo
7.
J Org Chem ; 87(6): 4112-4123, 2022 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-35258307

RESUMEN

An inexpensive copper-catalyzed sequential reaction process, proceeding via a nucleophilic attack of amine to Cu-carbene generated in situ from heterocyclic N-tosylhydrazone precursors followed by a 1,2-H shift/oxidative cyclization cascade of N-ylides, has been described, smoothly generating the corresponding structurally various spiro-dihydropyrrolo[1,2-a]quinoxaline derivatives. Furthermore, the significance of this protocol can be also highlighted by its diverse conversions of the synthetic compounds to the potentially bioactive molecules such as the 2-substituted pyrrolo[1,2-a]quinoxalins.


Asunto(s)
Cobre , Quinoxalinas , Compuestos de Anilina , Catálisis , Ciclización , Estructura Molecular
8.
Angew Chem Int Ed Engl ; 61(37): e202205790, 2022 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-35856897

RESUMEN

We report the discovery of an unusual halohydrin dehalogenase, HHDHamb, that can work under relatively low acidic conditions and extremely low temperatures for the bio-nitration of epoxides using nitrite as a nitrating agent. The bio-nitration strategy exhibits high chemo-, regio-, and enantioselectivity, catalyzing the kinetic resolution of various epoxides to enantiopure ß-nitroalcohols with nitro-bearing stereocenters in up to 41 % isolated yield and >99 % enantiomeric excess (ee). Additionally, the bio-nitration method displays a high reaction efficiency and can be performed on a gram scale. We also solved the crystal structure of HHDHamb to understand the possible structural determinants of chemoselectivity control in the bio-nitration reaction.


Asunto(s)
Compuestos Epoxi , Hidrolasas , Compuestos Epoxi/química , Hidrolasas/metabolismo , Cinética , Estereoisomerismo
9.
Angew Chem Int Ed Engl ; 61(52): e202212589, 2022 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-36328962

RESUMEN

Expanding the enzymatic toolbox for the green synthesis of valuable molecules is still of high interest in synthetic chemistry and the pharmaceutical industry. Chiral thiiranes are valuable sulfur-containing heterocyclic compounds, but relevant methods for their enantioselective synthesis are limited. Herein, we report a biocatalytic thionation strategy for the enantioselective synthesis of thiiranes, which was developed based on the halohydrin dehalogenase (HHDH)-catalyzed enantioselective ring-opening reaction of epoxides with thiocyanate and a subsequent nonenzymatic rearrangement process. A novel HHDH was identified and engineered for enantioselective biocatalytic thionation of various aryl- and alkyl-substituted epoxides on a preparative scale, affording the corresponding thiiranes in up to 43 % isolated yield and 98 % ee. Large-scale synthesis and useful transformations of chiral thiiranes were also performed to demonstrate the utility and scalability of the biocatalytic thionation strategy.


Asunto(s)
Compuestos Epoxi , Compuestos Epoxi/química , Estereoisomerismo , Biocatálisis
10.
Org Biomol Chem ; 19(21): 4720-4725, 2021 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-33969846

RESUMEN

An organometal catalytic conversion of 3-aminooxindoles for the diastereo- and enantioselective synthesis of homoallylic aminooxindoles has been described. The asymmetric allylic alkylation of 3-aminooxindoles with allyl carboxylates proceeded smoothly to afford a series of chiral 3-allyl-3-aminooxindoles. This work offers an alternative route to build these scaffolds. The application of this protocol is also highlighted by a significant conversion of products to the potential applicable spiro[indoline-3,2'-pyrrolidin]-2-one derivatives.

11.
Org Biomol Chem ; 18(6): 1112-1116, 2020 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-31984976

RESUMEN

A palladium-catalyzed [2 + 2 + 1] domino annulation of 3-iodochromones, α-bromo carbonyl compounds, and tetracyclododecene (TCD) is described. This approach provides a facile, efficient and atom-economical route to a variety of chromone-containing polycyclic compounds bearing fused/bridged-ring systems in good yields (up to 81%) with excellent diastereoselectivities (99 : 1 dr in all cases).

12.
J Org Chem ; 84(7): 4381-4391, 2019 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-30865449

RESUMEN

An organocatalyzed dearomative aza-Michael/Michael addition cascade of 2-nitrobenzofurans and 2-nitrobenzothiophenes with 2-aminochalcones has been developed, opening a new channel to access a series of optically active tetrahydrobenzofuro[3,2- b]quinolines and tetrahydrobenzo[4,5]thieno[3,2- b]quinolines bearing three contiguous stereocenters with excellent diastereo- and enantioselectivities (all cases >20:1 dr, up to 99% ee). This study features the first asymmetric dearomative cascade reaction of 2-nitrobenzofurans and 2-nitrobenzothiophenes beginning with aza-Michael addition. The potential applications of the methodology were demonstrated by the preparative-scale experiment and the versatile transformations of the products.

13.
J Org Chem ; 83(10): 5771-5777, 2018 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-29673248

RESUMEN

An efficient organocatalyzed enantioselective conjugated addition of sodium bisulfite to ß-trifluoromethyl-α,ß-unsaturated ketones using a cinchona alkaloid-derived squaramide catalyst is presented. A series of optically active sulfonic acids, bearing a tertiary stereocenter connecting a CF3 group and a SO3H group, were obtained in excellent yields with high enantioselectivities (up to 99% yield and 97% ee) under mild conditions. This method will provide an efficient, economic, and green route to access chiral sulfonic acid compounds.

14.
J Org Chem ; 83(12): 6556-6565, 2018 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-29863343

RESUMEN

Herein is disclosed a selective and facile approach for the construction of CF2H-containing pyrazolo[1,5- c]quinazolines from easily accessible 3-ylideneoxindoles and in situ generated CF2HCHN2. The reaction involving a [3 + 2] cycloaddition/1,3-H shift/rearrangement/dehydrogenation cascade proceeded smoothly at room temperature in the absence of catalyst and additive. Moreover, this metal-free process along with mild conditions is desirable and valuable for the pharmaceutical industry. Importantly, this reaction features a broad substrate scope, good functional group tolerance, and gram-scale synthesis.

15.
J Org Chem ; 83(17): 10465-10475, 2018 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-29966096

RESUMEN

A highly regio- and stereoselective [3 + 2] cycloaddition reaction for constructing novel 3,3'-cyclopentenyldispirooxindoles incorporating two adjacent quaternary spirostereocenters is reported. Under the mild conditions, the asymmetric annulation of isatin-derived MBH carbonates with 3-methyleneoxindoles involving a chiral tertiary amine catalyst provides the corresponding dispirooxindole frameworks with an extraordinary level of enantioselective control. Further synthetic utility of this method was demonstrated by the gram-scale experiment and simple transformation of the obtained product. Moreover, a plausible mechanism for this annulation reaction was also proposed on the basis of the control experiments.

16.
Org Biomol Chem ; 16(10): 1636-1640, 2018 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-29451583

RESUMEN

An asymmetric organocatalytic vinylogous Mannich reaction of 3-methyl-5-arylfuran-2(3H)-ones with N-(2-pyridinesulfonyl)imines has been developed with 5 mol% thiourea-tertiary amine as the catalyst. A series of δ-amino γ,γ-disubstituted butenolides bearing adjacent quaternary and tertiary stereocenters are efficiently obtained with satisfactory results (up to 90% yield, 90 : 10 dr, and 95 : 5 er).

17.
Org Biomol Chem ; 15(26): 5571-5578, 2017 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-28639676

RESUMEN

An efficient [3 + 2] cycloaddition of 3-ylideneoxindoles with in situ generated CF2HCHN2 for the syntheses of spirooxindoles has been developed. This methodology gives access to a range of relatively complex spirooxindoles featuring a CF2H group and three contiguous stereogenic centers in up to 84% yield and 99 : 1 trans/cis.

18.
Org Biomol Chem ; 14(4): 1395-401, 2016 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-26677092

RESUMEN

An unprecedented reaction between indolin-2-ones and α-substituted ketones has been developed. Using this protocol, a wide range of biologically important 3-hydroxy-3-phenacyloxindole derivatives could be obtained in good yield (up to 93%) under mild reaction conditions. A possible mechanism of this reaction was tentatively proposed based on some control experiments and MS spectrometry analysis.


Asunto(s)
Indoles/química , Indoles/síntesis química , Cetonas/química , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular , Oxindoles
19.
Yao Xue Xue Bao ; 51(7): 1117-20, 2016 07.
Artículo en Zh | MEDLINE | ID: mdl-29897210

RESUMEN

In this study, seven bibenzyl compounds were isolated from the stem of Dendrobium nobile by silica gel, MCI column chromatographic and preparative HPLC technology. By using spectroscopic techniques including NMR and MS, these compounds were identified as 4,α-dihydroxy-3,5,3'-trimethoxybibenzyl (1), 4,5-dihydroxy-3,3',α-trimethoxybibenzyl (2), 4,4'-dihydroxy-3,5,3'-trimethoxybibenzyl (3), 4,5-dihydroxy-3,3'-dimethoxybibenzyl(4), 4,3'-dihydroxy-3,5-dimethoxybibenzyl (5), 5,4'-dihydroxy-3,3'-dimethoxybibenzyl (6) and 5,3'-dihydroxy-3-methoxybibenzyl (7). Compound 1 is a new compound and compound 4 was isolated from this plant for the first time.


Asunto(s)
Bibencilos/química , Dendrobium/química , Tallos de la Planta/química , Bibencilos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética
20.
J Food Sci Technol ; 53(2): 1178-88, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27162397

RESUMEN

Effect of transglutaminase (TGM) and ascorbic acid (AA) on composite sweet potato - wheat dough functional and rheological properties was studied. Partial substitution of wheat flour with sweet potato flour at the level of 20 % significantly (P ≤ 0.05) reduced glutenin, gliadin, dough stability, protein weakening, storage modulus (G') and viscous modulus (G″). Mixolab revealed that both TGM and AA treated dough had stability and protein weakening closed to wheat dough (control), with TGM treated dough having the highest values. TGM Introduced new cross-link bonds as shown by the change of amino acid concentration, leading to an increase in storage modulus (G') and viscous modulus (G″), with G' being higher at all levels of TGM concentration. The opposite was observed for composite dough treated with AA as measured by controlled - stress rheometer. TGM treatment increased glutenin and gliadin content. Compared with the control, dough treated with AA exhibited high molecular weight of polymers than TGM treated dough. The results indicate that the TGM and AA modification of the mixolab and dynamic rheological characteristics (G' and G″) dependent on the changes of GMP, glutenin, gliadin and protein weakening in the composite dough. TGM and AA treatment could improve functional and rheological properties of sweet potato - wheat dough to levels that might be achieved with normal wheat bread. However, it's extremely important to optimize the concentrations of both additives to obtain the optimum response.

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