Using Quinolin-4-Ones as Convenient Common Precursors for a Metal-Free Total Synthesis of Both Dubamine and Graveoline Alkaloids and Diverse Structural Analogues.

The Rutaceae family is one of the most studied plant families due to the large number of alkaloids isolated from them with outstanding biological properties, among them the quinoline-based alkaloids Graveoline 1 and Dubamine 2. The most common methods for the synthesis of alkaloids 1 and 2 and their derivatives involves cycloaddition reactions or metal-catalyzed coupling processes but with some limitations in scope and functionalization of the quinoline moiety. As a continuation of our current studies on the synthesis and chemical transformation of 2-aminochalcones, we are reporting here an efficient metal-free approach for the total synthesis of alkaloids 1 and 2 along with their analogues with structural diversity, through a two-step sequence involving intramolecular cyclization, oxidation/aromatization, N-methylation and oxidative C-C bond processes, starting from dihydroquinolin-4-ones as common precursors for the construction of the structures of both classes of alkaloids.

Frommelt Attitude Toward Care of the Dying Scale Form B: Validation for Spanish health professionals.

OBJECTIVE: The aim of this study is to culturally adapt and validate the Frommelt Attitude Toward Care of the Dying Scale Form B (FATCOD-B) in Spanish health professionals. METHOD: A cultural adaptation and scale validation was carried out to evaluate the validity of appearance, content and construct, reliability and feasibility. The psychometric validation of the FATCOD-B was carried out on a sample of 2,446 Spanish physicians, nurses, psychologists, and social workers and students of these disciplines, between January 2017 and December 2018. This sample was selected by intentional sampling. Descriptive statistics were used to characterize the sample. An exploratory multi-group factor analysis was performed, internal consistency was evaluated by calculating Cronbach's α and stability by test-retest. RESULTS: A total of 2,446 people participated in the study, 1,134 students and 1,312 professionals. The exploratory multi-group factor analysis revealed a two-dimensional factor structure, with a total of 17 items retained in the model from the 30 of the original scale. The results showed that this version has adequate reliability (α = 0.79) and for each subscale, and stability (ICC = 0.843, p < 0.001). SIGNIFICANCE OF RESULTS: FATCOD has been used with physicians and nurses from different countries. However, no reports have been found in the literature of its use with psychologists and social workers. It is important to have an instrument that allows us to know the attitudes of these professionals since they are all directly involved in the care of patients at the end of their lives and their families. The Spanish version of FATCOD-B has proven to be a reliable and valid instrument for its use in Spanish health professionals while allowing comparisons between disciplines.

A Schmidt rearrangement-mediated synthesis of novel tetrahydro-benzo[1,4]diazepin-5-ones as potential anticancer and antiprotozoal agents.

Novel tetrahydro-5H-benzo[e][1,4]diazepin-5-ones, several of them, containing the quinoline pharmacophore, were synthesized via a Schmidt rearrangement from their corresponding 1,2,3,4-tetrahydro-4-quinolones mediated by the NaN3/H2SO4 reaction conditions. Twelve of the obtained compounds were in vitro screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where compound 24a presented a remarkable activity against 58 of the 60 cancer cell lines, with the most important GI50 values ranging from 0.047 to 8.16 µM and LC50 values ranging from 9.4 to > 100 µM. Additionally, some of them were evaluated as antimalarial, antitrypanosomal and antileishmanial agents. The best antimalarial response was observed for compound 22g with an EC50 = 13.61 µg/mL for Plasmodium falciparum, while compound 24d exhibited high activity against Trypanosoma cruzi. and Leishmania (V) panamensis with EC50 = 2.78 µg/mL and 3.35 µg/mL respectively.

Theoretical investigation of the selectivity in intramolecular cyclizations of some 2'-aminochalcones to dihydroquinolin-8-ones and indolin-3-ones.

The selectivity of the intramolecular cyclizations of a series of 2'-aminochalcones was investigated with an approach that combines spin-polarized conceptual density functional theory and energy calculations. To that aim, condensed-to-atoms electrophilic Fukui functions, f NN (+) (r), were utilized as descriptors of the proclivity for nucleophilic attack of the NH2 group on the unsaturated α and ß carbons. The results of our model are in excellent agreement with the experimental available evidence permitting us in all cases to predict when the cyclization processes led to the formation of 5-exo and 6-endo products.

1-(6-Amino-1,3-benzodioxol-5-yl)-3-(2-oxo-1,2-dihydroquinolin-3-yl)prop-2-enone: a sheet built by pi-stacking of hydrogen-bonded chains of rings.

The bond distances in the molecule of the title compound, C(19)H(14)N(2)O(4), provide evidence for electronic polarization in the aminoarylpropenone fragment and for bond fixation in the quinolinone unit. Molecules are linked by N-H...O and C-H...O hydrogen bonds into chains in which centrosymmetric rings of R(2)(2)(8) and R(2)(2)(18) types alternate, and these chains are linked into sheets by a single aromatic pi-pi stacking interaction.

Conformational and configurational disorder in 6-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5H-1,3-dioxolo[4,5-g]quinolin-8(5H)-one and 6-(1,3-benzodioxol-5-yl)-6,7-dihydro-5H-1,3-dioxolo[4,5-g]quinolin-8-one: a hydrogen-bonded chain of rings and pi-stacked hydrogen-bonded chains.

In 6-(3,4,5-trimethoxyphenyl)-6,7-dihydro-5H-1,3-dioxolo[4,5-g]quinolin-8(5H)-one, C(19)H(19)NO(6), (I), the six-membered heterocyclic ring adopts a conformation intermediate between envelope and half-chair forms; it is disordered over two enantiomeric configurations, with occupancies of 0.879 (3) and 0.121 (3), leading to positional disorder of the 3,4,5-trimethoxyphenyl unit. In 6-(1,3-benzodioxol-5-yl)-6,7-dihydro-5H-1,3-dioxolo[4,5-g]quinolin-8-one, C(17)H(13)NO(5), (II), the molecules are similarly disordered, with occupancies of 0.866 (4) and 0.134 (4). The molecules in (I) are linked by one three-centre N-H...(O)(2) hydrogen bond and one two-centre C-H...O hydrogen bond to form a complex chain of rings whose formation is reinforced by two independent aromatic pi-pi stacking interactions. In (II), a single N-H...O hydrogen bond links the molecules into a simple chain, and pairs of chains are linked by a single aromatic pi-pi stacking interaction.

6-(4-Bromophenyl)-6,7-dihydro-1,3-dioxolo[4,5-g]quinolin-8(5H)-one: bilayers built from N-H...O, C-H...O and C-H...pi(arene) hydrogen bonds.

Molecules of the title compound, C(16)H(12)BrNO(3), exhibit a polarized molecular-electronic structure. A combination of one N-H...O hydrogen bond and one C-H...O hydrogen bond links the molecules into sheets, and pairs of sheets are linked into bilayers by a single C-H...pi(arene) hydrogen bond.