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1.
J Org Chem ; 89(4): 2649-2655, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38279928

RESUMO

A very short stereoselective synthesis of enantiomerically pure (3S, 4aS, 10aR)-quinagolide has been developed. The key steps involved are a copper-catalyzed regioselective arylation of (S)-epichlorohydrin with 1,6-dimethoxynaphthalene and a diastereoselective trans-reduction of a cyclic enamine intermediate. The possibility to use both enantiomers of epichlorohydrin and the diastereodivergency found in the reduction process paves the way for a general preparation also in the nonracemic form of chiral trans-fused 3-substituted octahydrobenzo[g]quinolines that are privileged structures in medicinal chemistry.

2.
Org Biomol Chem ; 21(31): 6389-6396, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37492953

RESUMO

The stereoselective reduction of a diastereoisomeric mixture of benzo[g]octahydroquinolinium ion was examined in detail. A diastereoselective borohydride reduction in combination with an efficient deacylative enzymatic resolution of its ß-aminoester precursor are the key steps for a stereoselective installation of the three chiral centres present in the (3S,4aS,10aR)-eutomer of the medicinal drug quinagolide. The obtained data paves the way for an easy and practical attainment of chiral 3-substituted octahydrobenzo[g]quinolines that are privileged structures in medicinal chemistry.

3.
Molecules ; 26(23)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34885983

RESUMO

The possibility to form new C-B bonds with aziridines using diboron derivatives continues to be a particularly challenging field in view of the direct preparation of functionalized ß-aminoboronates, which are important compounds in drug discovery, being a bioisostere of ß-aminoacids. We now report experimental and computational data that allows the individuation of the structural requisites and of reaction conditions necessary to open alkyl aziridines using bis(pinacolate)diboron (B2pin2) in a regioselective nucleophilic addition reaction under copper catalysis.

4.
Org Biomol Chem ; 19(42): 9190-9198, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34492677

RESUMO

Chiral heteropolycyclic structures are widespread in compounds of high pharmaceutical relevance. In particular, linear fused pyran-dioxane based polycycles can be found in several naturally occurring molecules, and among them, cardiac glycosides and antibiotic spectinomycin are characterized by a cis-cisoid-trans geometry. Then, the stereocontrol in the synthesis of this type of polycyclic scaffold is of primary importance. Herein, we present two novel linear fused pyran-dioxane based bi- and tricycles, synthesized with total stereoselectivity from a glycal derived vinyl epoxide. The straightforward methodology described involves a substrate-dependent stereospecific glycosylation step followed by an intramolecular SN2' conjugate addition process, leading to a pyran-dioxane-cyclohexane tricycle with a cis-cisoid-trans stereochemistry, in agreement with the geometry of many natural products. The stereochemical analysis of these compounds, which was realized by a combined NMR/computational approach, is also reported.

5.
Molecules ; 25(8)2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32326095

RESUMO

γ- and δ-Oxoesters are easily available starting materials that have been sparingly used in some organocatalyzed reactions proceeding with a high enantioselectivity. In our experimentation we found that the use of these compounds as the enolizable (nucleophilic) component in organocatalyzed Mannich-type reactions using in situ-generated cyclic N-acyl iminium ions gave low diastereoselectivity and low to moderate values of enantioselectivity. This significant drop of facial selectivity with respect to simple aliphatic aldehydes has been rationalized by means of density functional theory (DFT) calculations.


Assuntos
Íons/química , Cetosteroides/química , Catálise , Teoria da Densidade Funcional , Isoquinolinas/química , Lactonas/química , Bases de Mannich/química , Metais , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Estereoisomerismo
6.
Chirality ; 31(7): 522-533, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31090981

RESUMO

The direct heterofunctionalization of acyclic α,ß-unsaturated aldehydes with N-acylquinolinium ions contemplating the formation of two stereocentres is studied using dienamine catalysis. This work gives some new experimental insights on the remote stereocontrol in dienamine catalysis using unbiased aliphatic systems and large electrophiles, pointing to a (Z)-preference of the reactive configuration of the second double bond.

7.
Chirality ; 31(2): 127-137, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30566766

RESUMO

The direct catalytic α-amidoalkylation of dihydroquinolines with aldehydes bearing oxygen functionalities at different positions in a Mannich-type reaction has been studied. ß-Alkoxy-aldehyde 1d gave high enantioselectivity, albeit with an inherently poor diastereoselectivity, while the use of α-alkoxy aldehydes 1c was detrimental also to enantioselectivity. Mannich-type reactions have been studied for the first time using new chiral carbohydrate-derived aldehydes 1a,b showing a reactivity markedly influenced by the presence of water. The chiral glycidic backbone showed a slight but significant influence on the overall stereochemical outcome only when present in α-position of the aldehyde. The absolute stereochemistry of the products was studied by electronic circular dichroism (ECD) spectra and compared with theoretical calculations. ECD analysis easily provides the absolute configuration of 1,2-dihydroquinoline derivatives such as quinoline-1(2H)-carboxylates.

8.
J Org Chem ; 83(19): 12221-12228, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30212634

RESUMO

The particular nature of tetrahydropyrido[4,3- e]-1,4,2-dioxazines of type 1 allows the regio- and stereoselective obtainment of substituted N-carbamoyl tetrahydropyridines by common reducing agents. A completely novel, biologically active, bicyclic 1,3-diaza-4-oxa-[3.3.1]-nonene scaffold can be generated by the use of lithium triethylborohydride through unprecedented cascade syn-SN2' reduction/carbamate reduction/cyclization reactions. The remarkable regioselectivity switches in the allylic reduction process have been rationalized with the aid of computational studies.

9.
Phys Chem Chem Phys ; 18(15): 10499-506, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-27031566

RESUMO

We present a simulation of the photodynamics of benzophenone for the first 20 ps after n →π* excitation, performed by trajectory surface hopping calculations with on-the-fly semiempirical determination of potential energy surfaces and electronic wavefunctions. Both the dynamic and spin-orbit couplings are taken into account, and time-resolved fluorescence emission is also simulated. The computed decay time of the S1 state is in agreement with experimental observations. The direct S1→ T1 intersystem crossing (ISC) accounts for about 2/3 of the S1 decay rate. The remaining 1/3 goes through T2 or higher triplets. The nonadiabatic transitions within the triplet manifold are much faster than ISC and keep the population of T1 at about 3/4 of the total triplet population, and that of the other states (mainly T2) at 1/4. Two internal coordinates are vibrationally active immediately after n →π* excitation: one is the C[double bond, length as m-dash]O stretching and the other one is a combination of the conrotatory torsion of phenyl rings and of bending involving the carbonyl C atom. The period of the torsion-bending mode coincides with oscillations in the time-resolved photoelectron spectra of Spighi et al. and substantially confirms their assignment.

10.
Dalton Trans ; 43(2): 495-504, 2014 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-24121665

RESUMO

The 1 : 2 molar reactions of MoCl5, in dichloromethane at room temperature, with tetrahydrofuran (thf), tetrahydropyran (thp), dioxane and tetrahydrothiophene (tht) afforded, respectively, [Mo(O)Cl3(thf)]2, 1, and MoCl4(L)2 (L = thp, 2; dioxane, 3; tht, 4), in 81-87% yields. The molecular structures of 1, 2 and 4 were ascertained by X-ray diffractometry. DFT and spectroscopic (IR, NMR) studies were carried out in order to shed light on thermodynamic and kinetic aspects of the reaction pathways.


Assuntos
Cloretos/química , Compostos Heterocíclicos/química , Molibdênio/química , Oxigênio/química , Enxofre/química , Cinética , Modelos Moleculares , Conformação Molecular , Teoria Quântica , Temperatura , Termodinâmica
11.
Phys Chem Chem Phys ; 15(47): 20651-61, 2013 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-24189815

RESUMO

We present on the fly surface hopping simulations of the dynamics of photoexcited acetone in the n → π* band, taking into account both the spin-orbit and the dynamic couplings and allowing for the C-C bond dissociation. The S0, S1, T1 and T2 states were considered and the propagation time was 50 ps. According to the simulation results, after excitation to S1 both Internal Conversion (IC) to S0 and InterSystem Crossing (ISC) to T1 or T2 take place at comparable rates; T2 plays an important role and the simultaneous treatment of the spin-orbit and dynamic couplings is shown to be mandatory to describe the photodynamics. We propose a mechanism that explains the observed fast and slow decay rates of the S1 state of acetone.


Assuntos
Acetona/química , Luz , Modelos Químicos , Fotólise , Teoria Quântica , Propriedades de Superfície , Termodinâmica
12.
Chirality ; 23(9): 820-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22135811

RESUMO

A convenient method for the stereoselective synthesis of diasteroisomeric vinyl epoxides (-)-2α and (-)-2ß, the carba analogs of D-galactal and D-allal-derived vinyl epoxides 1α and 1ß, has been elaborated starting from tri-O-acetyl-D-glucal. The key step of this synthesis is an application of the known Claisen thermal rearrangement of a glucal derivative, the vinyl allyl ether (+)-3b, which allows to switch the glycal structure into the corresponding carba analog scaffold. Epoxides (-)-2α and (-)-2ß derive from the same synthetic intermediate, the trans diol (+)-5.


Assuntos
Carbaçúcares/química , Carbaçúcares/síntese química , Compostos de Epóxi/química , Compostos de Epóxi/síntese química , Galactose/análogos & derivados , Galactose/síntese química , Galactose/química , Conformação Molecular , Estrutura Molecular , Estereoisomerismo
13.
J Comput Chem ; 31(14): 2612-9, 2010 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-20740561

RESUMO

Azidolysis of epoxides followed by reduction of the intermediate azido alcohols constitutes a valuable synthetic tool for the construction of beta-amino alcohols, an important chemical functionality occurring in many biologically active compounds of natural origin. However, depending on conditions under which the azidolysis is carried out, two regioisomeric products can be formed, as a consequence of the nucleophilic attack on both the oxirane carbon atoms. In this work, predictive models for quantitative structure-reactivity relationships were developed by means of multiple linear regression, k-nearest neighbor, locally weighted regression, and Gaussian Process regression algorithms. The specific nature of the problem at hand required the creation of appropriate new descriptors, able to properly reflect the most relevant features of molecular moieties directly involved in the opening process. The models so obtained are able to predict the regioselectivity of the azidolysis of epoxides promoted by sodium azide, in the presence of lithium perchlorate, on the basis of steric hindrance, and charge distribution of the substituents directly attached to the oxirane ring.


Assuntos
Amino Álcoois/síntese química , Simulação por Computador , Compostos de Epóxi/química , Azida Sódica/química , Algoritmos , Amino Álcoois/química , Catálise , Compostos de Lítio/química , Percloratos/química , Relação Quantitativa Estrutura-Atividade , Estereoisomerismo
14.
Org Lett ; 11(12): 2675-8, 2009 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-19456164

RESUMO

The glycosylation of alcohols by the new diastereoisomeric d,l-6-deoxy-N-Cbz-imino glycal-derived allyl N-nosyl aziridines 5 and 6 affords, after deprotection of the 4-(N-nosylamino) group, the corresponding 2,3-unsaturated-N-Cbz-imino-O-glycosides bearing a free amino group on C(4) through a completely 1,4-regio- and substrate-dependent stereoselective glycosylation process.


Assuntos
Aminoglicosídeos/síntese química , Aziridinas/química , Glicosídeos/síntese química , Imino Açúcares/química , Álcoois/química , Aminoglicosídeos/química , Glicosídeos/química , Glicosilação , Estrutura Molecular , Estereoisomerismo
15.
Org Lett ; 9(22): 4479-82, 2007 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-17900130

RESUMO

Diastereoisomeric D,L-N-Cbz-imino glycal-derived allyl epoxides 5 and 6 have been synthesized, and their addition reactions with alcohols examined. The reactions lead to the corresponding 2,3-unsaturated-aza-O-glycosides through a new, completely regioselective 1,4-addition process which proceeds with complete substrate-dependent stereoselectivity.

16.
J Org Chem ; 71(4): 1696-9, 2006 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-16468826

RESUMO

The reaction of the new D-galactal-derived allylic aziridine 1beta with O-nucleophiles (alcohols and monosaccharides) affords, in a high to complete beta-stereoselectivity, the corresponding 2,3-unsaturated-beta-O-glycosides bearing a beta-N-functionality at C4.


Assuntos
Aziridinas/química , Galactose/química , Glicosídeos/síntese química , Álcoois/química , Monossacarídeos/química , Estereoisomerismo
17.
J Org Chem ; 69(1): 150-7, 2004 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-14703391

RESUMO

The addition reaction of monomeric lithium enolate (Z)-1, derived from propiophenone, to propene oxide 2, was examined to clarify the exact geometry of the transition state (TS) involved in this type of reaction. The eight possible TSs and the corresponding pathways, four leading to syn gamma-hydroxy ketone (gamma-HK) 3 and four leading to anti gamma-HK 4, were compared, using the B3LYP/6-31+G(d)//B3LYP/6-31+G(d) theory level in vacuo and in the presence of the reaction solvent (toluene/hexane). In every case, the favored pathway involves a TS where the enolate C=C and the epoxide C-C are in a gauche relationship and where the Li(+) is stabilized by some C-C and C-H sigma bonds of epoxide 2.

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