Biomedical subjects
Publications and source records attributed to Anxin Wu.
Two novel diastereoselective three-component reactions of alkenes or 3,4-dihydro-(2H)-pyran with urea/thiourea-aldehyde mixtures are described. [reaction: see text]
[reaction: see text] A novel and efficient carbon-carbon double-bond formation reaction via coupling of aryl or heteroaryl methyl ketones has been developed. A dimethyl sulfoxide-iodine-CuO system was proven to be efficient for this reaction and afforded the expected products in good yields. A new synthetic strategy, a self-sorting tandem reaction, was involved in this type of reaction and was presented for the first time.
A novel three-component, one-pot condensation yielding 2-amino-4H-1,3-oxazines or 2-amino-4H-1,3-thiazines from alkynes, urea or thiourea, and aldehydes is described. [reaction: see text]
Self-sorting-the ability to efficiently distinguish between self and nonself-is common in nature but is still relatively rare in synthetic supramolecular systems. We report a 12-component mixture comprising 1-11 and KCl that undergoes thermodynamically controlled self-sorting in aqueous solution based on metal-ligand, ion-dipole, electrostatic, charge-transfer interactions, as well as the hydrophobic effect. We refer to this molecular ensemble-characterized by high-fidelity host-guest interactions between components-as a social self-sorting system to distinguish it from narcissistic self-sorting systems based on self-association processes. The influence of several key variables-temperature, pH, concentration, and host/guest stoichiometry-was explored by a combination of simulation and experiment. Variable temperature NMR experiments, for example, revealed a kinetically controlled irreversible process upon cycling from 298 to 338 K, which is an emergent property of this molecular ensemble. Variable pH and concentration experiments, in contrast, did not reveal any emergent properties of the molecular ensemble. Simulations of a four-component mixture establish that by proper control of the relative magnitude of the various equilibrium constants, it is possible to prepare socially self-sorted mixtures that are responsive (irresponsive) to host/guest stoichiometry over narrow (broad) ranges. The 12-component mixture is relatively irresponsive to host/guest stoichiometry. Such social self-sorting systems, like their natural counterparts, have potential applications as chemical sensors, as artificial regulatory elements, and in the preparation of biomimetic systems.
We report the synthesis and characterization of eight C-shaped methylene-bridged glycoluril dimers (1-8) bearing hydrogen-bonding amide groups on their aromatic rings. Compounds 1-6 undergo tight dimerization in CDCl3 solution (Ks > 9 x 10(5) M(-1)); binary mixtures of 1-7 form mixtures of homodimers and heterodimers in moderately selective dimerization processes (0.23 < or = Keq < or = 768; 0.253 < or = chiAB < 0.933). The high affinity formation of 1.1-6.6 is due to the commensurate nature of the geometrical constraints imposed by the pi-pi interactions and only two hydrogen bonds. The differential response of the strengths of the pi-pi interactions and H-bonds of 2.2 to changes in solvent polarity--from C6D6 to D2O--results in the formation of a solvent-independent isostructural aggregate that exhibits high affinity dimerization across the full range of solvents.
In this paper, we pose the question of whether self-sorting in designed systems is exceptional behavior or whether it is likely to become a more general phenomenon governing molecular recognition and self-assembly. To address this question we prepared a mixture comprising two of Davis' self-assembled ionophores, Rebek's tennis ball and calixarene tetraurea capsule, Meijer's ureidopyrimidinone, Reinhoudt's calixarene bis(rosette), and two molecular clips in CDCl(3) solution and observed the behavior of this ensemble by (1)H NMR. As hypothesized, high-fidelity self-sorting behavior was observed. The influence of several key variables-temperature, concentration, equilibrium constants, and the presence of competitors-on the fidelity of self-sorting is described. These results show that self-sorting is neither the exception nor the rule. They suggest, however, that the subset of known molecular aggregates that exceed the criteria required for thermodynamic self-sorting is larger than previously appreciated and potentially quite broad.
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Methylene-bridged glycoluril dimers are the fundamental building blocks of cucurbituril (CB[6]), its homologues (CB[n]), and its derivatives. This paper describes three complementary methods for the synthesis of C- and S-shaped methylene-bridged glycoluril dimers (29-34 and 37-44). For this purpose, we prepared glycoluril derivatives (1a-d) bearing diverse functionalities on their convex face. These glycoluril derivatives were alkylated under basic conditions (DMSO, t-BuOK) with 1,2-bis(halomethyl)aromatics 6-15 to yield 4a-d and 16-24, which contain a single aromatic o-xylylene ring and potentially nucleophilic ureidyl NH groups. Glycoluril derivatives bearing potentially electrophilic cyclic ether groups (5a-f) and 25-28 were prepared by various methods including condensation reactions in refluxing TFA containing paraformaldehyde. The condensation reactions of 4a-d and 16-24 with paraformaldehyde under anhydrous acidic conditions (PTSA, ClCH(2)CH(2)Cl, reflux) give, in most cases, the C-shaped and S-shaped methylene-bridged glycoluril in good to excellent yields. In many cases, the C-shaped compound is formed preferentially with high diastereoselectivity. Cyclic ethers 5a,d-f and 25-26 undergo highly diastereoselective dimerization reactions to yield methylene-bridged glycoluril dimers with the formal extrusion of formaldehyde. Last, it is possible to perform selective heterodimerization reactions using both cyclic ethers and glycoluril derivatives bearing ureidyl NH groups. These reactions deliver the desired C- and S-shaped heterodimers with low to moderate diastereoselectivities. This heterodimerization route is the method of choice in cases where the homodimerization reactions fail. The formation of side products (+/-)-35b and (+/-)-35d helps clarify the electronic requirements for a successful CB[n] synthesis. The X-ray structures of 30C, 38C, and 38S allow for a discussion of the structural features of this class of compounds.
The first total syntheses of the racemates of naturally occurring macrophyllin-type bicyclo[3.2.1]octanoid neolignans, kadsurenin C 3 and kadsurenin L 4, were accomplished starting from vanillin and resorcinol. The acid-catalyzed rearrangement of hydrobenzofuranoid neolignans into bicyclo[3.2.1]octanoid neolignans was used as the key step.
Cucurbit[6]uril (CB[6]) is a macrocyclic compound, prepared in one pot from glycoluril and formaldehyde, whose molecular recognition properties have made it the object of intense study. Studies of the mechanism of CB[n] formation, which might provide insights that allow the tailor-made synthesis of CB[n] homologues and derivatives, have been hampered by the complex structure of CB[n]. By reducing the complexity of the reaction to the formation of S-shaped (12S-18S) and C-shaped (12C-18C) methylene bridged glycoluril dimers, we have been able to probe the fundamental steps of the mechanism of CB[n] synthesis to a level that has not been possible previously. For example, we present strong evidence that the mechanism of CB[n] synthesis proceeds via the intermediacy of both S-shaped and C-shaped dimers. The first experimental determination of the relative free energies of the S-shaped and C-shaped dimers indicates a thermodynamic preference (1.55-3.25 kcal mol(-)(1)) for the C-shaped diastereomer. This thermodynamic preference is not because of self-association, solvation, or template effects. Furthermore, labeling experiments have allowed us to elucidate the mechanism of this acid-catalyzed equilibrium between the S-shaped and C-shaped diastereomers. The equilibration is an intramolecular process that proceeds with high diastereoselectivity and retention of configuration. On the basis of the broad implications of these results for CB[n] synthesis, we suggest new synthetic strategies that may allow for the improved preparation of CB[n] (n > 8) and CB[n] derivatives from functionalized glycolurils.
We have discovered a novel class of (E)-3-acyloxy-4-(arylmethylidene)cyclodeca-1,5-diynes which exhibit promising enediyne-like DNA cleavage and cytotoxic activities. LC-MS analysis of the incubation mixture (pH 8.5, 37 degrees C) confirmed formation of 10-membered ring enediyne presumably via an allylic cation and suggested that the 1,4-benzenoid diradical might be one of the active species for DNA damage and cytotoxicity.