In 1981, the macrocyclic methylene-bridged glycoluril hexamer (CB[6]) was dubbed "cucurbituril" by Mock and co-workers because of its resemblance to the most prominent member of the cucurbitaceae family of plants--the pumpkin. In the intervening years, the fundamental binding properties of CB[6]-high affinity, highly selective, and constrictive binding interactions--have been delineated by the pioneering work of the research groups of Mock, Kim, and Buschmann, and has led to their applications in waste-water remediation, as artificial enzymes, and as molecular switches. More recently, the cucurbit[n]uril family has grown to include homologues (CB[5]-CB[10]), derivatives, congeners, and analogues whose sizes span and exceed the range available with the alpha-, beta-, and gamma-cyclodextrins. Their shapes, solubility, and chemical functionality may now be tailored by synthetic chemistry to play a central role in molecular recognition, self-assembly, and nanotechnology. This Review focuses on the synthesis, recognition properties, and applications of these unique macrocycles.

Im Jahre 1981 tauften Mock und Mitarbeiter das makrocyclische methylenverbrückte Glycoluril‐Hexamer (CB[6]) auf den Namen “Cucurbituril” – da ihre Form einem Kürbis ähnelt, dem bekanntesten Mitglied der Cucurbitaceae‐Familie in der Pflanzenwelt. In den folgenden Jahren wurden die grundlegenden Bindungseigenschaften von CB[6] – die hohe Affinität und Selektivität sowie der Einschluss von Gästen – in bahnbrechenden Arbeiten der Gruppen von Mock, Kim und Buschmann aufgezeigt; es folgten Anwendungen in der Wasseraufarbeitung, künstlichen Enzymen und molekularen Schaltern. Erst vor kurzem wuchs die Cucurbit[n]uril‐Familie um Homologe (CB[5]–CB[10]), Derivate, Verwandte und Analoga, sodass sie nun die Molekülgrößen von α‐, β‐ und γ‐Cyclodextrinen umfasst und übersteigt. Auch die Formen, Löslichkeiten und chemischen Funktionalitäten können inzwischen durch spezielle Synthesen den Erfordernissen angepasst werden. Durch diese Eigenschaften sind die Cucurbiturile prädestiniert für eine zentrale Rolle in molekularer Erkennung, Selbstorganisation und Nanotechnologie. Dieser Aufsatz stellt Synthesen, Erkennungseigenschaften und Anwendungen dieser einzigartigen Makrocyclen vor.

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Molecular recognition and self-assembly in aqueous solution have experienced rapid growth in recent years. The use of -, -, and -cyclodextrins, calixarenes, and cyclophanes have served as the platforms for molecular recognition in aqueous solution. Recently, the investigation of an alternative platform based on cucurbituril has become the focus of several research groups. The rigid structure and capability of forming complexes with molecules and ions through hydrophobic, iondipole and hydrogen-bonding interactions make cucurbituril an attractive candidate as a synthetic receptor as well as a building block for the construction of supramolecular architectures.However, before cucurbituril can be used to supplant the more common platforms as the molecule of choice for molecular recognition and self-assembly in aqueous solution, several advances must be made: 1) cucurbiturils must become available in a variety of sizes, 2) their solubility must be improved, and 3) synthetic procedures must be advanced to include the ability to selectively generate specific cucurbituril homologues, derivatives, and analogues. To help rationalize the high yields obtained in these macrocyclization reactions, we performed mechanistic studies of model methylene bridged glycoluril dimers.The molecular recognition properties of a water soluble cucurbit[6]uril analogue in aqueous buffer toward a variety of guests including alkanediamines, aromatics, amino acids, and nucleobases were studied by fluorescence spectroscopy.For the alkanediamines studied, as the length of the alkane is increased between the amines, the association constants also increase. The CB [6] analogue is capable of forming strong complexes with guests containing aromatic rings with association constants (K a ) ranging from 10 2 to 10 6 M -1 due to the favorable -interactions that occur between the host and the aromatic portion of the guest while encapsulated in its hydrophobic cavity. CUCURBIT[N]URIL ANALOGUES

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.