Asunto(s)
Aminas/química , Yodo/química , Lactonas/química , Urea/química , Catálisis , Estructura Molecular , EstereoisomerismoRESUMEN
A second bite of the apple: A new and highly efficient synthesis of the propargylic mesylate fragment of azadirachtin has been accomplished (see scheme; Bn = benzyl, Ms = methanesulfonyl, PMB = para-methoxybenzyl, TBDPS = tert-butyldiphenylsilyl). An enantioselective catalytic hetero Diels-Alder reaction sets up the stereocenter at C15, which then controls the installation of the remaining functionality in a total of only 17 steps.
Asunto(s)
Limoninas/síntesis química , Catálisis , Lactonas/química , Limoninas/química , Mesilatos/síntesis química , Mesilatos/química , EstereoisomerismoRESUMEN
Azadirachtin has been the subject of intensive research within the scientific community ever since its isolation from the neem tree in 1968. There are now over 1000 publications relating to this natural product which cover all aspects of structural, biological and synthetic studies. Herein, we describe the worldwide synthesis efforts towards this fascinating molecule.
Asunto(s)
Limoninas/síntesis química , Azadirachta/química , Limoninas/química , Limoninas/aislamiento & purificaciónRESUMEN
We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.
Asunto(s)
Insecticidas/síntesis química , Limoninas/síntesis química , Insecticidas/química , Limoninas/química , Conformación Molecular , EstereoisomerismoRESUMEN
The use of magnesium nitride (Mg 3N 2) as a convenient source of ammonia has been explored for the direct transformation of esters to primary amides. Methyl, ethyl, isopropyl, and tert-butyl esters are converted to the corresponding carboxamides in good yields (75-99%).
Asunto(s)
Amidas/síntesis química , Amoníaco/química , Amoníaco/síntesis química , Compuestos de Magnesio/química , Amidas/química , Ésteres/química , Estructura Molecular , EstereoisomerismoRESUMEN
Magnesium nitride (Mg 3N 2) has been investigated for the preparation of dihydropyridines. This is a commercially available, bench-stable solid that generates ammonia upon treatment with protic solvents. The main features of the process are the facile reaction setup and good yields obtained in the majority of cases.
Asunto(s)
Amoníaco/química , Amoníaco/síntesis química , Dihidropiridinas/síntesis química , Compuestos de Magnesio/química , Aldehídos/química , Dihidropiridinas/química , Ésteres/química , Estructura Molecular , EstereoisomerismoRESUMEN
The synthesis of five natural products (3, 6, 7, 10, and 14), isolated from the Indian neem tree Azadirachta indica, is reported from a common intermediate (2). The judicious choice of transacetalization conditions allows efficient access to both the azadirachtinin (9 and 10) and the azadirachtin (3, 6, 7, and 14) skeletons.
Asunto(s)
Azadirachta/química , Productos Biológicos/síntesis química , Limoninas/síntesis química , Productos Biológicos/química , India , Limoninas/química , Estructura MolecularRESUMEN
The synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. These compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an NFkappaB glucocorticoid receptor (GR) agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). Quinolones, indoles, and C- and N-linked quinolines are some of the heterocycles that provide efficacy selectivity. For example, the isoquinoline 49D1E2 has NFkappaB agonism with pIC50 of 8.66 (89%) and reduced efficacy in MMTV agonism (6%), and the quinoline 55D1E1 has NFkappaB agonism with pIC50 of 9.30 (101%) and reduced efficacy in MMTV agonism with pEC50 of 8.02 (47%). A description of how a compound from each class is modeled in the active site of the receptor is given.
Asunto(s)
Antiinflamatorios no Esteroideos/síntesis química , Receptores de Glucocorticoides/agonistas , Tetrahidronaftalenos/síntesis química , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Sitios de Unión , Línea Celular , Agonismo Parcial de Drogas , Humanos , Virus del Tumor Mamario del Ratón/genética , Modelos Moleculares , Imitación Molecular , FN-kappa B/genética , Receptores de Glucocorticoides/antagonistas & inhibidores , Estereoisomerismo , Relación Estructura-Actividad , Tetrahidronaftalenos/química , Tetrahidronaftalenos/farmacología , Transcripción Genética/efectos de los fármacos , Activación Transcripcional/efectos de los fármacosRESUMEN
The syntheses of three decalin-based tert-thiols displaying varying degrees of solubility in aqueous milieu are described. The S-nitroso derivatives of these compounds have also been prepared and the structures of two of these determined by single crystal X-ray diffraction. These compounds have been designed for studying the interaction of nitric oxide (NO) with thiols under physiological conditions.