How does the problem-oriented innovation system (PIS) help in the management of cardiovascular diseases?

Introduction: Cardiovascular diseases are a multifaceted and complex problem in the health system that can change the priorities of the economic, social, and even political systems of countries. Therefore, as a grand challenge (GC), its management requires adopting a systematic, interdisciplinary, and innovative approach. In Iran, the most common causes of death, have changed from infectious and diarrheal diseases to cardiovascular diseases since 1960. Methods: In this study, the novel framework of the problem-oriented innovation system (PIS) has been used, and cardiovascular diseases in Iran have been selected as a case study. To this end, first, the main challenges related to cardiovascular diseases in Iran were identified in two layers of "governance-centered" (including legal and policy gaps, insufficient education, financing, lack and unbalanced distribution of medical personnel) and "society driven" (including unhealthy diet and lifestyle, uncontrolled and hard-to-regulate factors, and high costs) through a library research. Then, the functional-structural framework of the problem-oriented innovation system was used to analyze cardiovascular diseases and provide policy recommendations. Results: The findings indicate that based on the eight functions of the problem-oriented innovation system, an important part of cardiovascular diseases can be managed and controlled in three short-term, medium-term, and long-term periods. Conclusion: Increasing public awareness in the form of university courses, participation of the government with the private sector in building and equipping specialized cardiovascular centers, creating an electronic health record from birth, implementing a family health plan focusing on less developed areas, supporting agriculture and guaranteeing the purchase of agricultural products and healthy food, increasing the capacity of accepting students in medical and paramedical fields, and allocating pharmaceutical currency in the form of pharmaceutical subsidies directly to cardiovascular patients, are among the most important policy recommendations for this grand challenge.

Direct Conversion of Carboxylic Acids to Alkyl Ketones.

An efficient and mild method for acyl-Csp3 bond formation based on the direct conversion of carboxylic acids has been established. This protocol is enabled by the synergistic, Ir-photoredox/nickel catalytic cross-coupling of in situ activated carboxylic acids and alkyltrifluoroborates. This versatile method is amenable to the cross-coupling of structurally diverse carboxylic acids with various potassium alkyltrifluoroborates, affording the corresponding ketones with high yields. In this operationally simple cross-coupling protocol, aliphatic ketones are obtained in one step from bench stable, readily available carboxylic acids.

Synergistic Visible-Light Photoredox/Nickel-Catalyzed Synthesis of Aliphatic Ketones via N-C Cleavage of Imides.

An electrophilic, imide-based, visible-light-promoted photoredox/Ni-catalyzed cross-coupling reaction for the synthesis of aliphatic ketones has been developed. This protocol proceeds through N-C(O) bond activation, made possible through the lower activation energy for metal insertion into this bond due to delocalization of the lone pair of electrons on the nitrogen by electron-withdrawing groups. The operationally simple and mild cross-coupling reaction is performed at ambient temperature and exhibits tolerance for a variety of functional groups.

Synergistic Photoredox/Nickel Coupling of Acyl Chlorides with Secondary Alkyltrifluoroborates: Dialkyl Ketone Synthesis.

Visible light photoredox/nickel dual catalysis has been employed in the cross-coupling of acyl chlorides with potassium alkyltrifluoroborates. This protocol, based on single-electron-mediated alkyl transfer, circumvents the restriction of using reactive alkylmetallic nucleophiles in transition-metal-catalyzed acylation and achieves a mild and efficient method for the synthesis of unsymmetrical alkyl ketones. In this approach, a variety of acyl chlorides have been successfully coupled with structurally diverse potassium alkyltrifluoroborates, generating the corresponding ketones with good yields.

Single-Electron Transmetalation: Photoredox/Nickel Dual Catalytic Cross-Coupling of Secondary Alkyl ß-Trifluoroboratoketones and -esters with Aryl Bromides.

The first cross-coupling of secondary alkyl ß-trifluoroboratoketones and -esters has been achieved through application of photoredox/nickel dual catalysis. Although the related ß-trifluoroboratoamides have been effectively cross-coupled via Pd-catalysis, the corresponding ketones and esters had proven recalcitrant prior to this report. Reactions occur under mild conditions, and a variety of functional groups and sterically and electronically diverse reaction partners are tolerated.

Visible Light Photoredox Cross-Coupling of Acyl Chlorides with Potassium Alkoxymethyltrifluoroborates: Synthesis of α-Alkoxyketones.

A visible-light, single-electron-transfer (SET), photoredox cross-coupling for the synthesis of α-alkoxyketones has been developed. In this method, various aliphatic and aromatic acyl chlorides were successfully coupled with structurally diverse potassium alkoxymethyltrifluoroborates, producing the corresponding α-alkoxyketones with high yields. In this operationally simple and mild cross-coupling protocol, the desired ketones are obtained in one step from bench stable starting materials by a bond connection that is unique to both alkylboron chemistry and photoredox/Ni catalysis.

Toward Efficient Nucleophilic Azaborine Building Blocks for the Synthesis of B-N Naphthyl (Hetero)arylmethane Isosteres.

To develop a method for the synthesis of a class of azaborines, potassium 2-(trifluoroboratomethyl)-2,1-borazaronaphthalenes have been synthesized to serve as nucleophilic building blocks. In palladium-catalyzed cross-coupling reactions with (hetero)aryl chlorides they serve to produce a variety of pseudobenzylic (hetero)aryl substituted azaborines. Potassium 2-(trifluoroboratomethyl)-2,1-borazaronaphthalenes are crystalline solids that are more stable than 2-(chloromethyl)-2,1-borazaronaphthalenes and have a broader substrate scope in cross-coupling reactions compared to their pseudobenzylic chloride counterparts.

Accessing 2-(hetero)arylmethyl-, -allyl-, and -propargyl-2,1-borazaronaphthalenes: palladium-catalyzed cross-couplings of 2-(chloromethyl)-2,1-borazaronaphthalenes.

The synthesis of 2-(chloromethyl)-2,1-borazaronaphthalene has provided an opportunity to expand dramatically the functionalization of the azaborines. This azaborinyl building block can serve as the electrophile in palladium-catalyzed cross-coupling reactions to form sp(3)-sp and sp(3)-sp(2) bonds. The cross-coupling reactions of 2-(chloromethyl)-2,1-borazaronaphthalene with potassium (hetero)aryl- and alkenyltrifluoroborates as well as terminal alkynes provides access to a variety of novel azaborines, allowing a library of pseudobenzylic substituted azaborines to be prepared from one common starting material.

Accessing an azaborine building block: synthesis and substitution reactions of 2-chloromethyl-2,1-borazaronaphthalene.

One major synthetic route to the synthesis of benzyl amines, ethers, and esters is the nucleophilic substitution of a benzylic halide. To develop a method for the facile synthesis and functionalization of the isosteric azaborines, 2-chloromethyl-2,1-borazaronaphthalene has been synthesized in one step to afford a similar common precursor to a benzylic halide. This B-N isostere has been shown to be an effective building block by serving as an electrophile in substitution reactions with a large variety of nucleophiles.

(3-Amino-phen-yl)diphenyl-phosphine oxide-2-propanol (1/1).

The title compound, C(18)H(16)NOP·C(3)H(8)O, was synthesized by the reduction of (3-nitro-phen-yl)diphenyl-phosphine oxide in the presence of 2-propanol as recrystallization solvent. There are two molecules in the asymmetric unit. Each P atom is tetra-coordinated by three C and one O atom from two phenyl fragments, one aniline group and one double-bonded O atom in a distorted tetra-hedral geometry. C-H⋯π and N-H⋯π inter-actions are present. In the crystal structure, a wide range of non-covalent inter-actions consisting of hydrogen bonding [of the types of O-H⋯O, N-H⋯O and C-H⋯O, with D⋯A distances ranging from 2.680 (3) to 3.478 (3) Å] and π-π [centroid-centroid distance of 3.7720 (15) Å] stacking inter-actions connect the various components into a supra-molecular structure.