RESUMEN
Novel imidazole-containing boronic acid and palladium hybrid catalysis for regioselective O-allylation of carbohydrates has been developed. This catalytic process enables the introduction of a useful allyl functional group into the equatorial hydroxy group of cis-1,2-diols of various carbohydrates with low catalyst loading and excellent regioselectivities. This is the first report on hybrid catalysis in combination with a Lewis base-containing boronic acid and a transition metal complex.
RESUMEN
The stereoselective 5-endo-trig oxygenative cyclization of α,ß-unsaturated oximes was achieved using molecular oxygen (O2) and a manganese catalyst. Several 4-hydroxy-4,5-dihydroisoxazoles were obtained in high yields by directly incorporating O2 from the atmosphere (eliminating the necessity for a pure oxygen environment) and using an unprecedentedly low loading of Mn(acac)3 (as little as 0.020 mol %) without additional additives. Because of its desirable features, such as operational simplicity, inexpensive catalyst, mild reaction conditions (open flask conditions at room temperature), and broad substrate compatibility, this novel reaction provides an attractive synthetic approach to producing 4-hydroxy-4,5-dihydroisoxazoles.
RESUMEN
2,5-Diketopiperazines (DKPs) with hydroxymethyl functional groups are essential structures found in many bioactive molecules and functional materials. We have established a simple protocol for the concise synthesis of this type of DKPs through diboronic acid anhydride-catalyzed hydroxy-directed peptide bond formations. The sequential reactions in this report, which consist of three steps, an intermolecular catalytic condensation reaction in which water is the only byproduct, a simple deprotection of the nitrogen-protecting group, and an intramolecular cyclization, enabled the synthesis of functionalized DKPs in high to excellent yields without any intermediate purification. The utility of this protocol has been demonstrated by synthesizing natural products, phomamide and Cyclo(Deala-l-Leu).
RESUMEN
Boronic acid-catalyzed regioselective Koenigs-Knorr-type glycosylation is presented. The reaction of an unprotected or partially protected glycosyl acceptor with a glycosyl halide donor in the presence of silver oxide and a low catalytic amount of imidazole-containing boronic acid was found to proceed smoothly, which enables construction of a 1,2-trans glycosidic linkage with high regioselectivities. This is the first example of the use of a boronic acid catalyst to initiate regioselective glycosylation via the activation of cis-vicinal diols in glycosyl acceptors.
Asunto(s)
Ácidos Borónicos , Glicósidos , Catálisis , GlicosilaciónRESUMEN
The first concise total syntheses of O-3'-senecioyl α-bisabolol ß-D-fucopyranoside (4a) and O-3'-isovaleroyl α-bisabolol ß-D-fucopyranoside (4b) were achieved through final-stage site-selective acylation via the activation of cis-vicinal diols by imidazole-containing boronic acid catalysts as a key step. This synthetic method was also effective for the syntheses of unnatural analogues with modified acyl side chains or carbohydrate moiety.
Asunto(s)
Productos Biológicos/síntesis química , Ácidos Borónicos/química , Sesquiterpenos Monocíclicos/química , alfa-L-Fucosidasa/síntesis química , Acilación , Catálisis , Dominio Catalítico , Imidazoles/química , Estructura Molecular , EstereoisomerismoRESUMEN
A concise total synthesis of seminolipid, a sulfoglycolipid, has been achieved; key features include regioselective, tin-free sulfation of allyl ß-d-galactopyranoside using 2,6-bis(trifluoromethyl)phenylboronic acid as protective reagent, stereoselective epoxidation, and site-selective acylation. The utility of this divergent synthetic approach to introduce 2,2,2-trichloroethyl-protected sulfate group at an early stage without toxic and environmentally unfavorable tin reagents was demonstrated by the syntheses of three seminolipid analogues with different side-chains from the common intermediate.
RESUMEN
A novel aerobic manganese-catalyzed oxophosphorylation reaction of carbon-carbon double bonds of styrene derivatives and vinyl ethers using diethyl H-phosphonates was developed. This direct transformation of alkenes to ß-ketophosphonate readily proceeded at room temperature via the direct incorporation of molecular oxygen present in air (open flask).
Asunto(s)
Carbono/química , Complejos de Coordinación/química , Manganeso/química , Oxígeno/química , Estirenos/química , Compuestos de Vinilo/química , Catálisis , Organofosfonatos/química , Oxidación-Reducción , FosforilaciónRESUMEN
We report the first synthesis of a series of bisdesmosidic oleanolic acid saponins using microflow reactor Comet X-01 via a continuous flow glycosylation-batch deprotection sequence. The main results of this study can be summarized as follows: (1) The microfluidic glycosylation of oleanolic acid at C-28 was achieved in quantitative yield and was applied to the synthesis of six C-28-monoglycosidic saponins. (2) The microfluidic glycosylation of oleanolic acid at C-3 was achieved in good yield without orthoester byproduct formation and was applied to the synthesis of three bisdesmosidic saponins. (3) The continuous synthesis of saponins via a microfluidic glycosylation-batch deprotection sequence was achieved in four steps involving two purifications. Thus, the continuous microfluidic glycosylation-deprotection process is expected to be suitable for the preparation of a library of bisdesmosidic oleanolic acid saponins for in vivo pharmacological studies.
RESUMEN
The synthesis of sialic acids and their analogs was accomplished based on substrate-controlled asymmetric aldol reactions between sterically complicated aldehydes easily prepared from commercially available carbohydrates and a novel pyruvic acid oxabicyclo[2.2.2]octyl orthoester. Systematic aldol reaction studies using chiral aldehydes revealed that α,ß,γ-benzyloxy-substituted aldehydes with an α,ß-anti relative configuration preferentially provided the Felkin products with the 4,5-anti configuration with high diastereoselectivity. The relative ß,γ-configuration in α,ß,γ-benzyloxy-substituted aldehydes with an α,ß-syn arrangement exerted a secondary effect on the diastereoselectivity of the stereogenic center formed in aldol reactions, and α,ß-syn-ß,γ-anti benzyloxyaldehyde exhibited superior diastereoselectivity to α,ß-syn-ß,γ-syn benzyloxyaldehyde to yield the Felkin products.
RESUMEN
A series of new simplified oleanolic acid saponins with a glycosyl ester moiety at C28, were efficiently prepared. Furthermore, the effect of nasal administration of the synthetic oleanolic acid saponins on the nasal anti-influenza virus antibody titer against secondary nasal inoculation of the influenza split vaccine was examined. The result revealed cinnamoyl saponin as a suitable candidate vaccine adjuvant.
Asunto(s)
Adyuvantes Inmunológicos/síntesis química , Adyuvantes Inmunológicos/farmacología , Vacunas contra la Influenza/administración & dosificación , Mucosa Nasal/efectos de los fármacos , Ácido Oleanólico/química , Saponinas/síntesis química , Saponinas/farmacología , Adyuvantes Inmunológicos/química , Administración Intranasal , Animales , Ratones , Ratones Endogámicos BALB C , Saponinas/química , Análisis Espectral/métodosRESUMEN
Although aqueous ammonia is an inexpensive and readily available safe source of ammonia, there have been no successful studies on direct catalytic dehydrative amidations of carboxylic acids with aqueous ammonia. In this study, we report a catalytic methodology for the synthesis of primary amides through diboronic acid anhydride (DBAA)-catalyzed dehydrative condensation of carboxylic acids with aqueous ammonia as the amine substrate.
RESUMEN
The development of Ir-catalyzed asymmetric hydrogenation of α-amino-ß-keto ester hydrochlorides is described. This reaction proceeds through a dynamic kinetic resolution to produce anti-ß-hydroxy-α-amino acid esters in a high diastereo- and enantioselective manner. Mechanistic studies have revealed that this unique asymmetric hydrogenation proceeds through reduction of the ketone moiety via the five-membered transition state involving the chelation between the oxygen of the ketone and the nitrogen of the amine function. The relationship studies between the hydrogen pressure and the stereoselectivity have disclosed two mechanisms dependent on hydrogen pressure. Under low hydrogen pressure (<15 atm), the reaction rate proportionally increased with the hydrogen pressure. However, under the high hydrogen conditions, the reaction rate exponentially accelerated along with the increasing hydrogen pressure, which suggests the participation of two or more of hydrogen atoms.
Asunto(s)
Aminoácidos/química , Hidrocarburos Clorados/síntesis química , Iridio/química , Catálisis , Ésteres , Hidrocarburos Clorados/química , Hidrogenación , Cinética , Espectroscopía de Resonancia Magnética , Estructura Molecular , EstereoisomerismoRESUMEN
We report the catalytic direct peptide bond formations via dehydrative condensation of ß-hydroxy-α-amino acids, affording the serine, threonine, or ß-hydroxyvaline-derived peptides in high to excellent yields with high functional group tolerance, minimum epimerization, and excellent chemoselectivity. The key to the success of these atom-economical transformations is the use of diboronic acid anhydride catalyst for the hydroxy-directed reactions.
RESUMEN
The first successful example of the direct synthesis of Weinreb amides using catalytic hydroxy-directed dehydrative amidation of carboxylic acids using the diboronic acid anhydride catalyst is described. The methodology is applicable to the concise syntheses of eight α-hydroxyketone natural products, namely, sattabacin, 4-hydroxy sattabacin, kurasoins A and B, soraphinols A and B, and circumcins B and C.
RESUMEN
Site-selective acylation of unprotected carbohydrates by using stable, storable, and easily handled imidazole-containing organoboronic acid catalysts is described. This catalytic process with low catalyst loading enables the introduction of a wide variety of acyl functional groups into the equatorial position of cis-vicinal diols in unprotected hexapyranosides with excellent site selectivity. This is the first example that uses a Lewis base-containing boronic acid to enhance the nucleophilicity of hydroxy groups.
RESUMEN
The direct catalytic dehydrative amidation of ß-hydroxycarboxylic acids with amines is described. A biphenyl-based diboronic acid anhydride with a B-O-B skeleton is shown to be an exceptionally effective catalyst for the reaction, providing ß-hydroxycarboxylic amides in high to excellent yields with a low catalyst loading (minimum of 0.01 mol %, TON up to 7,500). This hydroxy-directed amidation shows excellent chemoselectivity and is applicable to gram-scale drug synthesis.
RESUMEN
Homogeneous chiral nickel-bisphosphine complexes catalyze the asymmetric hydrogenation of alpha-amino-beta-keto ester hydrochlorides through dynamic kinetic resolution to efficiently afford anti-beta-hydroxy-alpha-amino esters with high diastereo- and enantioselectivities.
Asunto(s)
Aminas/química , Ácido Clorhídrico/química , Hidrógeno/química , Níquel/química , Fosfinas/química , Aminoácidos/química , Catálisis , Esterificación , Cinética , Ligandos , Estructura Molecular , Solventes , EstereoisomerismoRESUMEN
The application of 2,6-bis(trifluoromethyl)phenyl boronic acid ( o-FXylB(OH)2; o-FXyl = 2,6-(CF3)2C6H3) as a recoverable and reusable protective agent for diols is described. The resulting cyclic boronic esters are water- and air-stable and tolerant to various organic transformations. Moreover, they can be deprotected under mild conditions. This methodology was applied to the synthesis of a highly conjugated enetriyne natural product with anti-angiogenic activities.
RESUMEN
An efficient synthesis of (2S,3R)-3-hydroxy-3-methylproline (OHMePro), a component of polyoxypeptins, and relatives was achieved, in which an intramolecular asymmetric aldol reaction of the ketoaldehyde using OHMePro itself as an organocatalyst constitutes a key step.
RESUMEN
Anti-selective asymmetric hydrogenation of alpha-amino-beta-keto esters via dynamic kinetic resolution under low hydrogen pressure has been achieved by an easily-handled cationic iridium complex with tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BARF) as a counterion.