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.
A cavitand functionalized with a Kemp’s triacid derivative was used to catalyze the epoxide ring-opening cyclizations of 1,5-epoxyalcohols. A deep, cylindrical cavity containing electron-rich ...aromatic walls and an inwardly directed carboxylic acid displayed the necessary characteristics to bind different 1,5-epoxyalcohols and initiate their cyclization reactions. The reactions inside this synthetic receptor occurred in a catalytic and regioselective manner. These results highlight that the arrangement of functionality and unique solvation provided by the structured interiors of natural enzymes can be incorporated into synthetic systems having useful physical and chemical properties.
The cyclization reaction of an epoxyalcohol is catalyzed by a synthetic cavitand receptor with an inwardly directed carboxylic acid function. The receptor features a hydrophobic pocket in which the ...substrate is bound and positioned to react in a regioselective manner. The nature of this substrate−catalyst complex and its dynamic properties were investigated by NMR methods and with the aid of a model compound lacking the epoxide function. The kinetic parameters of the cyclization reaction were also studied. A catalytic cycle is proposed and diverse inhibition mechanisms are identified that parallel those encounterd in enzymology.
Natural inspiration: Based on the biosynthesis of squalene‐derived polyethers, a total synthesis of teurilene is described. The carbocation formation in the Nicholas reaction serves to control the ...initiation of a polyepoxide ring‐opening cascade. The three furan rings present in teurilene were obtained in excellent yield in one step. Boc=tert‐butoxycarbonyl, TMS=trimethylsilyl.
Using a 2 + 2 + 2 cycloaddition/Mitsunobu reaction sequence, a convenient synthesis to access new benzocyclotrimer analogues has been developed. The new receptors have the geometry and functionality ...capable of recognizing the tetramethylammonium ion in the gas phase and in solution.
A new series of hybrid dipeptide‐like organocatalysts based on pyranoid ϵ‐ or ζ‐amino acids and proline have been prepared for the asymmetric Michael addition of aldehydes to β‐nitrostyrenes. The ...reaction proceeds under mild conditions to afford a wide range of γ‐nitroaldehydes with up to 98% yield and up to 96% ee. These dipeptides are bifunctional organocatalysts, with a proline at the N‐terminus and a carboxylic acid at the C‐terminus. The tetrahydropyran unit embedded in the ϵ‐ or ζ‐amino acid induces a well‐defined conformation that is responsible for the catalysis. These dipeptides represent a new type of organocatalyst with a large number of possibilities to modulate their reactivity and selectivity.
An expedient methodology to synthesize macrocyclic compounds in one step based on the Nicholas reaction is disclosed. The key step features two intermolecular reactions followed by an intramolecular ...reaction from the starting dicobalt hexacarbonyl-propargylic complex. The macrocycles obtained were modified through 2 + 2 + 2 cycloaddition, generating two new C3-symmetric hexasubstituted benzene structures suitable for molecular recognition purposes.
A simple and convenient one-pot protocol for the chemoselective C2-homologation of carbohydrate-derived glycols is described. The method comprises the chemoselective oxidation of the glycol to the ...corresponding hydroxyaldehyde and the subsequent Wittig alkenylation. In addition, the method does not need selective protective group manipulation, and it is safe, economical, fast (5 to 6 h), and bench-friendly. Its general utility is discussed.
The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to (+)-muconin, an ...acetogenin with remarkable cytotoxicity. A novel approach that enables the stereoselective synthesis of such a natural compound or its enantiomer from a common precursor is described. An additional advantage of the method is complete stereochemical control and the decrease in the number of chemical steps required, thus providing an enhancement of the overall yield. Antiproliferative studies against the human solid tumor cell lines showed that the aliphatic chain-THF/THP fragment of (+)-muconin has modest cytotoxic activity. The strategy opens the way to preparing novel bioactive acetogenin analogues by shorter synthetic routes.
Based on tetrapeptide AVPI we were able to design and synthesize a new simplified scaffold to inhibit the BIR3 domain of the XIAP protein at low micromolar range.
Based on tetrapeptide AVPI, we were ...able to design and synthesize a new simplified scaffold to inhibit the BIR3 domain of the XIAP protein at low micromolar range. The uncomplicated synthesis and the binding activity of the molecule disclosed here represent an attractive alternative to develop new compounds targeting the protein–protein interaction of XIAP/caspase9.
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