For molecular architectures based on dynamic covalent chemistry (DCvC), strict preorganization is a paradigmatic concept and the generally accepted strategy for their rational design. This results in ...the creation of highly rigid building blocks which are expected to fulfill the ideal geometry of the assembly, coming at a price that small geometric mismatches result in unpredicted and/or unproductive reaction outcomes. In this study, we show that feet of a tripodal platform have a great influence on the assembly of tetrahedral organic cages based on boronate ester formation. The aryl benzyl ether-functionalized building blocks perform significantly better than their alkyl-functionalized equivalents. Experimentally and using density functional theory geometry optimization of the cage structures, we prove that unexpectedly, this is not due to solubility but because of the enhanced capability of the aryl benzyl ether-functionalized building blocks to fit the ideal geometry of the assembly. This introduces the concept of building block adaptability to overcome geometrical mismatches in DCvC systems.
Ascorbic acid (vitamin C) has been used as a radical initiator in a metal‐free direct CH arylation of (hetero)arenes. Starting from an aniline, the corresponding arenediazonium ion is generated in ...situ and immediately reduced by vitamin C to an aryl radical that undergoes a homolytic aromatic substitution with a (hetero)arene. Notably, neither heating nor irradiation is required. This procedure is mild, operationally simple, and constitutes a greener approach to arylation.
Vitamin C oupling: A catalytic amount of ascorbic acid acted as a radical initiator in a metal‐free direct CH arylation of arenes and heteroarenes with anilines (see scheme; Boc=tert‐butoxycarbonyl). The reaction requires no heating or irradiation, is operationally simple, and constitutes a greener approach to arylation.
Directional bonding strategies guide the design of complex molecular architectures, yet challenges arise due to emergent behavior. Rigid structures face geometric constraints and sensitivity to ...mismatches, hindering the efficient assembly of molecular organic cages (MOCs). Harnessing intramolecular non‐covalent interactions offers a promising solution, broadening geometrical possibilities and enhancing adaptability to boost assembly yields. However, identifying these interactions remains challenging, with their full potential sometimes latent until final assembly. This study explores these challenges by synthesizing boronic acid tripods with varied oxygen positions at the tripodal feet and investigating their role in assembling tetrahedral boronate MOCs. Our results reveal substantial differences in the assembly efficiency among tripods. While the building blocks with oxygen in the benzylic position relative to the central aromatic ring form the MOCs in high yields, those with the oxygen atom directly bound to the central aromatic ring, only yield traces. Through X‐ray crystallography and DFT analyses, we elucidate how intramolecular interactions profoundly influence the geometry of the building blocks and cages in a relay‐like fashion, highlighting the importance of considering intramolecular interactions in the rational design of (supra)molecular architectures.
Latent intramolecular non‐covalent interactions (NCIs) within the building blocks play a crucial role in the assembly of molecular organic cages (MOCs) via Dynamic Covalent Chemistry (DCC). These intramolecular interactions emerge from induced conformational restrictions during cage assembly, ultimately dictating the reaction outcome in a relay‐like fashion.
Abstract
This account describes our studies on the synthesis of natural products that contain cyclic ethers in their structures. An overview of the main methodologies is presented and several total ...syntheses developed by the group are described. We also discuss new applications based on the use of Prins and Nicolas reactions as key steps in the preparation of oxygenated heterocyclic compounds.
1 Introduction
1.1 Natural Sources and Biogenesis
2 Carbon–Oxygen Bond-Formation Approach
2.1 Intramolecular Opening of Epoxy Alcohols and Related Bromo Cyclizations
2.2 Intramolecular Hetero-Michael Reaction of Alkoxy γ-Benzoyloxy α,β-Unsaturated Esters
2.3 Intramolecular Nicholas Reaction
3 Ring-Closing Metathesis of Unsaturated Linear Ethers
4 Prins Cyclization Promoted by Iron(III) salts
4.1 General Strategy
4.2 Cyclization Using Alkynols and the Formation of Vinyl Halides
4.3 The Use of Trimethylsilyl and Electron-Withdrawing Substituents in the Synthesis of 2,6-Disubstituted Tetrahydropyrans
4.4 Catalytic Prins Cyclization
4.5 Synthesis of Oxepanes
5 Summary
A new approach to lauroxanes by a powerful and highly convergent methodology based on iterative use of Co2(CO)6-acetylenic complexes is described. The strategy employs an intermolecular Nicholas ...reaction to form unsaturated branched linear ethers, a ring closing metathesis to obtain the cobalt complex cyclic ethers, and an isomerization promoted by montmorillonite K-10. A short synthesis of cyclic ethers of seven-, eight-, and nine-membered rings is described. Additionally, the methodology is exemplified by the formal synthesis of (+)-laurencin, a red algae metabolite.
The discovery of molecular organic cages (MOCs) is inhibited by the limited organic-chemical space of the building blocks designed to fulfill strict geometric requirements for efficient assembly. ...Using intramolecular attractive or repulsive non-covalent interactions to control the conformation of flexible systems can effectively augment the variety of building blocks, ultimately facilitating the exploration of new MOCs. In this study, we introduce a set of boronic acid tripods that were designed using rational design principles. Conformational control was induced by extending the tripod's arms by a 2,3-dimethylbenzene unit, leading to the efficient formation of a tetrapodal nanometer-sized boroxine cage. The new building block's versatility was demonstrated by performing cage metamorphosis upon adding an aromatic tetraol. This led to a quantitative boroxine-to-boronate transformation and a topological shift from tetrahedral to trigonal bipyramidal.
The conformational control of boronic acid building blocks allows efficient self-assembly into a tetrahedral boroxine cage. The nano-sized cage displays molecular metamorphosis, converting from a boroxine tetrapod to a boronate bipyramid.
We report a new and efficient synthetic strategy that allows access to flexible and functionalized benzocyclotrimers under mild conditions and in few steps. The Negishi cross-coupling reaction was ...used for the C-C bond formation, whereas intramolecular O-alkylations provided the oxepane rings.
•ONS contributes to increase energy, protein and nutrients in cancer patients.•Enhanced ONS increases the intake in cancer patients in worse clinical conditions.•Enhanced ONS for cancer had a high ...adherence, good tolerance, and acceptance.
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The aim of this study was to evaluate the impact of an enhanced ONS (enriched in EPA, DHA, leucine, and beta-glucans) on the dietary intake of cancer patients.
A randomized, double-blind, parallel, controlled, and multicenter clinical trial was conducted in patients with cancer and malnutrition. The trial compared prescribed dietary advice and two packs per day, for 8 weeks, of a hypercaloric (400 kcal/pack) and hyperproteic ONS (20 g/pack) with fiber and specific ingredients (leucine, EPA and DHA, and beta-glucans) (enhanced-ONS) versus an isocaloric and isoproteic formula (standard-ONS) without specific ingredients. Food intake was assessed with a 3-day dietary survey, and adherence to the supplement with a patient self-completed diary.
Thirty-seven patients completed the intervention period. The combined intervention of dietary advice and ONS managed to increase the energy intake of the overall cohort by 792.55 (378.57) kcal/day, protein by 40.72 (19.56) g/day. Increases in energy and nutrient intakes were observed in both groups, both in dietary intake and associated exclusively with the supplement. The group that received the enhanced-ONS ingested a greater volume of product when there was a greater severity of malnutrition; a tumor location in the head, neck, upper digestive area, liver, or pancreas; more advanced stages of the tumor; or the receipt of more than one antineoplastic treatment.
The use of an enhanced-ONS helps meet the nutritional requirements of cancer patients, especially those who have a more compromised clinical condition, with high adherence, good tolerance, and acceptance.
Cyclic products can be obtained through the intramolecular version of the Nicholas reaction, which requires having the nucleophile connected to the alkyne unit. Here, we report the synthesis of ...1-oxa-3-cyclooctynes starting from commercially available (1
,3
)-camphoric acid. The strategy is based on the initial preparation of propargylic alcohols, complexation of the triple bond with Co
(CO)
, and treatment with BF
·Et
O to induce an intramolecular Nicholas reaction with the free hydroxyl group as nucleophile. Finally, oxidative deprotection of the alkyne afforded the cyclooctynes in good yields. Notably, large-sized R substituents at the chiral center connected to the O atom were oriented in such a way that steric interactions were minimized in the cyclization, allowing the formation of cyclooctynes exclusively with
configuration, in good agreement with theoretical predictions. Moreover, preliminary studies demonstrated that these cyclooctynes were reactive in the presence of azides yielding substituted triazoles.
Honey samples (n = 126) from Castilla-La Mancha (Central Spain) were characterized based on their physicochemical properties and a melissopalynological analysis. The latter showed that Echium pollen ...type was the dominant palynomorph in most samples, representing at least 30% of the pollen in each sample. As anticipated, a relationship was observed between the proportion of this pollen and the properties of the honey. One goal of this study was to set a threshold that defines the percentage of pollen necessary for Viper's bugloss honey to be considered monofloral or multifloral. This is a mandatory requirement in light of the publication of the European Directive 2014/63/EU establishing the regulations governing the labelling and control of honey to eradicate fraud (BOE n° 147, June 2015). By analyzing how the proportions of Echium pollen type affected the physicochemical and sensory parameters of the honey, the honeys analyzed could be segregated into multifloral and monofloral honeys. The data indicates that the proportion of pollen necessary to discriminate monofloral Viper's bugloss honey lies at 70%.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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