RESUMO
As shown by X-ray crystallography, crystals of 3ß-acetoxy-16,17-seco-17,20-dioxopregn-5-ene-16-nitrile are dimorphic. The regioselectivity of the Norrish-Yang type II photocyclization under visible light of this steroidal 1,2-diketone, which bears primary, secondary, and tertiary nonequivalent abstractable γ-hydrogens, dramatically increases in the crystalline state of both polymorphs. X-ray crystallography and molecular mechanics calculations reveal crystal structure-solid state photochemistry relationships.
Assuntos
Cetonas , Luz , Ciclização , Fotoquímica , Cetonas/química , Cristalografia por Raios XRESUMO
The 1,5-HAT-1,2-(ester)alkyl radical migration (Surzur-Tanner rearrangement) radical/polar sequence triggered by alkoxyl radicals has been studied on a series of C-glycosyl substrates with 3-C-(α,ß-d,l-glycopyranosyl)1-propanol and C-(α-d,l-glycopyranosyl)methanol structures prepared from chiral pool d- and l-sugar. The use of acetoxy and diphenoxyphosphatoxy as leaving groups provides an efficient construction of 10-deoxy-1,6-dioxaspiro[4.5]decane and 4-deoxy-6,8-dioxabicyclo[3.2.1]octane frameworks. The alkoxyl radicals were generated by the reaction of the corresponding N-alkoxyphthalimides with group 14 hydrides [n-Bu3SnH(D) and (TMS)3SiH], and in comparative terms, the reaction was also initiated by visible light photocatalysis using the Hantzsch ester/fac-Ir(ppy)3 procedure. Special attention was devoted to the influence of the relative stereochemistry of the centers involved in the radical sequence on the reaction outcome. The addition of BF3â¢Et2O as a catalyst to the radical sequence resulted in a significant increase in the yields of the desired bicyclic ketals.
Assuntos
Hidrogênio , Octanos , Alcanos , CarboidratosRESUMO
The anomeric alkoxyl radical ß-fragmentation (ARF) of carbohydrates possessing an electron-withdrawing group (EWG) at C2, promoted by PhI(OAc)2/I2, gives rise to an acyclic iodide through which a pentavalent atom of phosphorus can be introduced via the Arbuzov reaction. After selective hydrolysis and subsequent cyclization, the phosphonate or phosphinate intermediates can be converted into 2-deoxy-1-phosphahexopyranose and 2-deoxy-1-phosphapentopyranose sugars. The ARF of carbohydrates with an electron-donor group (EDG) at C2 proceeds by a radical-polar crossover mechanism, and the cyclization occurs by nucleophilic attack of a conveniently positioned phosphonate or phosphinate group to the transient oxocarbenium ion. This alternative methodology leads to 5-phosphasugars with a 4-deoxy-5-phosphapentopyranose framework. The structure and conformation of the 2-oxo-1,2-oxaphosphinane and 2-oxo-1,2-oxaphospholane ring systems in different carbohydrate models have been studied by NMR and X-ray crystallography.
RESUMO
A simple and efficient radical C-H functionalization to access modified cyclodextrins (CDs) has been developed. The well-defined conformation of glycosidic and aglyconic bonds in α-, ß-, and γ-CDs favors the intramolecular 1,8-hydrogen atom transfer (HAT) promoted by the 6I-O-yl radical, which abstracts regioselectively the hydrogen at C5II of the contiguous pyranose. The C5II-radical evolves by a polar crossover mechanism to a stable 1,3,5-trioxocane ring between two adjacent glucoses or alternatively triggers the inversion of one α-d-glucose into a 5-C-acetoxy-ß-l-idose unit possessing a 1C4 conformation. The 6I,IV- and 6I,III-diols of α- and ß-CDs behave similarly to the monoalcohols, forming mostly compounds originating from two 1,8-HAT consecutive processes. In the case of 6I,II-diols the proximity of the two 6-O-yl radicals in adjacent sugar units allows the formation of unique lactone rings within the CD framework via a 1,8-HAT-ß-scission tandem mechanism. X-ray diffraction carried out on the crystalline 1,4-bis(trioxocane)-α-CD derivative shows a severe distortion toward a narrower elliptical shape for the primary face.
RESUMO
A simple method to modify the primary face of cyclodextrins (CDs) is described. The 6(I)-O-yl radical of α-, ß-, and γ-CDs regioselectively abstracts the H5(II), located in the adjacent D-glucose unit, by an intramolecular 1,8-hydrogen-atom-transfer reaction through a geometrically restricted nine-membered transition state to give a stable 1,3,5-trioxocane ring. The reaction has been extended to the 1,4-diols of α- and ß-CD to give the corresponding bis(trioxocane)s. The C2-symmetric bis(trioxocane) corresponding to the α-CD is a stable crystalline solid whose structure was confirmed by X-ray diffraction analysis. The calculated geometric parameters confirm that the primary face is severely distorted toward a narrower elliptical shape for this rim.
Assuntos
Ciclodextrinas/química , Cristalografia por Raios X , Glucose/química , Hidrogênio/química , Conformação Molecular , EstereoisomerismoRESUMO
A series of four α-diketones placed as 1α-pyruvoyl tethers on D-glucopyranose and D-glucopyranosiduronic acid skeletons was prepared in order to determine the influence of captodative and stereoelectronic effects on the regioselectivity of the hydrogen atom transfer (HAT) in Norrish typeâ II photochemical processes. We observed that the 1,5-HAT regioselectivity can be switched between the two potentially abstractable syn-1,3-diaxial hydrogens at H6 and H8. Highly unusual photoproducts from Norrish typeâ II photoelimination and Norrish-Yang photocyclization initiated by the excited internal carbonyl group were obtained, in some cases in excellent synthetic yield. The 1,5-HAT transition state in the Norrish typeâ II photoelimination was investigated by photochemical experiments in the crystalline state.
Assuntos
Carboidratos/química , Cetonas/química , Piruvatos/química , Ciclização , Estrutura Molecular , Processos Fotoquímicos , FotoquímicaRESUMO
The excitation of the innermost carbonyl of nono-2,3-diulose derivatives by irradiation with visible-light initiates a sequential Norrish typeâ II photoelimination and aldol cyclization process that finally gives polyfunctionalized cyclopentitols. The rearrangement has been confirmed by the isolation of stable acyclic photoenol intermediates that can be independently cyclized by a thermal 5-(enolexo)-exo-trig uncatalyzed aldol reaction with high diastereoselectivity. In this last step, the large deuterium kinetic isotope effect found for the 1,5-hydrogen atom transfer seems to indicate that the aldol reaction runs through a concerted pericyclic mechanism. Owing to the ready availability of pyranose sugars of various configurations, this protocol has been used to study the influence of pyranose ring-substituents on the diastereoselectivity of the aldol cyclization reaction. In contrast with other pyranose ring contraction methodologies no transition-metal reagents are needed and the sequential rearrangement occurs simply by using visible light and moderate heating (0 to 60 °C).
Assuntos
Carboidratos/síntese química , Aldeídos/química , Carboidratos/química , Ciclização , Cetonas/síntese química , Estrutura Molecular , Processos FotoquímicosRESUMO
A previously developed 1,8-hydrogen atom transfer (HAT) reaction promoted by 6-O-yl alkoxyl radicals between the two pyranose units in Hexp-(1â4)-Hexp disaccharides has been extended to other systems containing at least a furanose ring in their structures. In Penf-(1â3)-Penf (A) and Hexp-(1â3)-Penf (B) disaccharides, the 1,8-HAT reaction and concomitant cyclization to a 1,3,5-trioxocane ring are in competition with radical ß-scission of the C4-C5 bond and formation of dehomologated products. The influence of the stereoelectronic ß-oxygen effect on the ß-scission and consequently on the 1,8-HAT reaction has been studied using the four possible isomeric d-furanoses. d-xylo- and d-lyxo-derivatives afforded preferentially 1,8-HAT products, whereas d-arabino- and d-ribo-derivatives gave exclusively direct ß-scission of the alkoxyl radical. When the 6-O-yl radical is on a pyranose ring, as occurs in Penf-(1â4)-Hexp (C), it has been shown to provide the cyclized products exclusively.
Assuntos
Dissacarídeos/síntese química , Furanos/química , Hidrogênio/química , Ciclização , Dissacarídeos/química , Estrutura Molecular , EstereoisomerismoRESUMO
Extraintestinal features may be observed in patients with ulcerative colitis (UC). We describe a 69-year-old woman who was initially diagnosed as having polymyalgia rheumatica (PMR). Prednisone was progressively tapered to complete discontinuation a year and a half after PMR diagnosis. However, at that time, she started to complain of asthenia, abdominal cramping and pain on the left side, weight loss and bloody diarrhoea. A colonoscopy confirmed a diagnosis of left-sided UC. She experienced several flares of the disease that required admission and treatment with high-dose corticosteroids and azathioprine. Colectomy was performed as the disease became refractory to these therapies. Four months after surgery, when the patient was not receiving any corticosteroid therapy, she started to feel dull and achy pain in the thighs along with claudication of the lower limbs. An 18F-fluorodeoxyglucosepositron emission tomography with CT (FDG PET/CT) disclosed an inflammatory process with mild-moderate diffuse increased metabolism in the thoracic aorta and markedly increased FDG uptake in the in the femoral and posterior tibial arteries on both sides. Treatment with the anti-TNF-alpha monoclonal antibody-adalimumab (40 mg every 2 weeks subcutaneously) along with prednisone (initial dose 15 mg/day) yielded rapid improvement of symptoms. Also, a new FDG PET/CT performed 4 months later disclosed marked decrease of FDG uptake in the involved arteries.This report emphasises the importance of suspecting the presence of large- and medium-vessel vasculitis in a patient with UC presenting with musculoskeletal features. It also highlights the beneficial effect of TNF-antagonists in vasculitis associated to UC.
Assuntos
Colite Ulcerativa/complicações , Extremidade Inferior/irrigação sanguínea , Polimialgia Reumática/etiologia , Vasculite Sistêmica/etiologia , Idoso , Biópsia , Colectomia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Colonoscopia , Meios de Contraste , Quimioterapia Combinada , Feminino , Fluordesoxiglucose F18 , Humanos , Imunossupressores/uso terapêutico , Imagem Multimodal , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Vasculite Sistêmica/diagnóstico , Vasculite Sistêmica/tratamento farmacológico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Imagem Corporal TotalRESUMO
The stereochemical and conformational factors controlling the intramolecular hydrogen-atom transfer (HAT) reaction between the two pyranose units in a (1-->4)-O-disaccharide when promoted by a primary 6-O-yl radical are studied. Models with alpha-D-Glcp-(1-->4)-beta-D-Glcp, alpha-L-Rhamp-(1-->4)-alpha-D-Galp or alpha-D-Manp-(1-->4)-beta-L-Gulp skeletons led exclusively to the abstraction of the hydrogen from H--C-5' and the formation, through a nine-membered transition state, of a 1,3,5-trioxocane ring system in a stable boat-chair conformation. Notwithstanding, derivatives of alpha-L-Rhamp-(1-->4)-alpha-D-Glcp or alpha-D-Manp-(1-->4)-alpha-D-Galp exclusively abstract the hydrogen from H--C-1' through a seven-membered transition state and, therefore, lead to an interglycosidic spiro ortho ester.
Assuntos
Dissacarídeos/química , Hidrogênio/química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Estrutura Molecular , EstereoisomerismoRESUMO
The stereoselective reduction of hexopyranos-5'-yl radicals in alpha-D-Hex p-(1-->4)-D-Hex p disaccharide models is described. These radicals are generated from a 6-O-yl radical located in the other monosaccharic unit through a 1,8-hydrogen atom transfer. The reaction, which is strongly influenced by steric and stereoelectronic effects, permits in some cases the transformation of alpha-D-Hex p-(1-->4)-D-Hex p into beta-L-Hex p-(1-->4)-D-Hex p disaccharides in a single step with high diastereoselectivity.
Assuntos
Dissacarídeos/química , Radicais Livres/química , Hexoses/química , Hidrogênio/química , EstereoisomerismoRESUMO
The generation and fate of 2I-VII,3I-VII,6II-VII-icosa- O-methyl-ß-cyclomaltoheptaos-6I- O-yl radical under reductive conditions is described. Two radical cascade reactions are involved: the main one is triggered by a 1,8-HAT of the hydrogen at 5VIIC. The radical can reach the anomeric hydrogen at 1VC three sugar units ahead using a six-step sequence. The different hydrogen donor ability of the group 14 hydrides permits one to selectively stop the cascade at 5VIIC, 2VIC, and 4VIC to obtain ß-CD with a ß-l-Ido p unit, acyclic hepta-, and hexa-saccharide structures, respectively.
RESUMO
[reaction: see text] The stereochemical and conformational factors controlling the intramolecular hydrogen atom transfer (HAT) reaction between the two pyranose units in a (1-->4)-disaccharide when promoted by a primary 6-O-yl radical are studied. Models with alpha-d-Glcp-(1-->4)-beta-d-Glcp or alpha-l-Rhamp-(1-->4)-alpha-d-Galp skeletons lead exclusively to the abstraction of H-C-5' and the formation, through a nine-membered transition state, of a 1,3,5-trioxocane ring system in a stable boat-chair conformation. Notwithstanding, derivatives of alpha-l-Rhamp-(1-->4)-alpha-d-Glcp abstract exclusively H-C-1' through a seven-membered transition state and therefore lead to an interglycosidic spiro ortho ester.
Assuntos
Álcoois/química , Dissacarídeos/química , Hidrogênio/química , Modelos Biológicos , Radicais Livres/química , Maltose/química , Conformação Molecular , EstereoisomerismoRESUMO
A tandem 1,5-hydrogen atom transfer/radical oxidation/nucleophilic cyclization mechanism is proposed for the intramolecular hydrogen abstraction reaction promoted for primary carboxamidyl radicals. The electron-withdrawing capacity of the C-5 substituent can switch the reaction to give exclusively bicyclic spirolactams (6-oxa-1-azaspiro[4.5]decan-2-one) when R(1) = H or spirolactones (1,6-dioxaspiro[4.5]decan-2-one) when R(1) = OAc. With a substituent of medium polarity (R(1) = OMe), a mixture of lactones and lactams is formed.
RESUMO
Aziridine N-carbonyl radicals, generated by irradiating the corresponding S-oxalyl xanthates, undergo ring opening to give 2-isocyanato radicals, which can be trapped by an external olefin.
RESUMO
A simple transformation of the eight-carbon side chain of a natural spirostan sapogenin into the cephalostatin north 1 spiroketal moiety is described. This methodology, based on an intramolecular hydrogen abstraction reaction promoted by alkoxy radicals, permits the synthesis of C-22 and C-25 stereoisomers of the dioxaspiro[4.4]nonane cephalostatin ring system. The acid-catalyzed isomerization of the spirocenter in the different isomers is studied. [reaction: see text]
Assuntos
Fenazinas/síntese química , Plantas/química , Sapogeninas/química , Compostos de Espiro/síntese química , Esteroides , Cristalografia por Raios X , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
[reaction: see text] The alkoxy radical generated by reaction of 3,7-anhydro-2-deoxyoctitols with (diacetoxyiodo)benzene (DIB) and iodine abstracts regioselectively either the proton at C7 or that at C4 depending on the electronegativity of the substituent at C4. The correct election of this substituent can switch the reaction to give 2,9-dioxabicyclo[3.3.1]nonane or hexahydro-2H-furo[3,2-b]pyran ring systems.
Assuntos
Carboidratos/química , Radicais Livres/química , Hidrogênio/química , Indicadores e Reagentes , Modelos MolecularesAssuntos
Adenoma/cirurgia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/etiologia , Vasoespasmo Intracraniano/etiologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Osso Esfenoide/cirurgia , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/terapiaRESUMO
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