Methods are described for the chemo-and regioselective monofunctionalization of the secondary hydroxyl face of cyclodextrins. Monofunctionalization takes place either by nucleophilic epoxide opening of mono(2A,3A-anhydro)heptakis(6-0-teri-butyldimethylsilyl)-(2AS)-/?-cyclodextrin by ethylenediamine, lithium azide, or ammonia or by direct monoalkylation of one of the C(2)-hydroxyl groups of heptakis(6-0-tert-butyldimethylsilyl)cyclodextrins with primary alkyl bromides, with cyano-, ethynyl-, or ester-containing functional groups. The latter route enables the synthesis of mono(2A-0-(a-(4-(aminomethyl)tolyl))hexakis(2B,2c,2D,2E,2F,2G-0-methyl)heptakis(6-0-ter^butyldimeth-ylsilyl)-/3-cyclodextrin and its 2-aminomethyl isomer. These are lipophilic precursors for cyclodextrin derivatives having one reactive functional group and an enlarged molecular cavity formed by partial methylation of the secondary hydroxyl face. The direct monoalkylation route of the secondary face leaves the structure of the cavity intact, while this is distorted in the route using nucleophilic epoxide opening. Two amino-functionalized cyclodextrins were used for coupling reactions with a monofunctionalized calix [4]arene. In this way water-soluble cyclodextrin derivatives could be obtained of which the secondary faces were flexibly capped with a calix[4]arene moiety.

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P-Cyclodextrins appended with a calixL4larene moiety at the secondary face are very efficient host molecules for the fluorescent dyes I-anilino-8-naphthalenesulfonate and 2-p-toluidino-6-naphthalenesulfonate with unprecedented high complexation constants.Cyclodextrins are a unique group of naturally occurring cyclic D-glucose oligomers, capable of the complexation of hydrophobic guest molecules in aqueous solvents by predominantly hydrophobic interactions.' During complexation, the area of the hydrophobic surface, i.e. the interior of the cyclodextrin cavity and the hydrophobic part of the guest molecule, exposed to water is decreased. Binding constants of up to 10000 dm3mol-l are known, but stronger binding of guests is restricted because of the open ends of the molecular cylinder. The first cyclodextrin derivatives with an enhanced hydrophobic cavity were developed by the groups of Breslowz and TabushiI.3 by functionalization of the primary hydroxy face. Introduction of a (flexible) 2-naphthalenesulfonyl cap at the primary face, combined with modification of the secondary face with a 4-toluenesulfonyl group was achieved by Ueno et aZ.4 These cyclodextrin-based receptors show significantly increased binding affinities for several specific guest molecules because of additional shielding of the hydrophobic guest from the aqueous environment. Recently, D' Alessandro et aZ.5 reported a cyclodextrin derivative with two different binding sites by linking the primary side of P-cyclodextrin (cycloheptaamylose) to one of the carboxyl groups of tetrakis(hydr0xycar-bony1methoxy)calixarene via an ethylene diamine spacer. However, no binding properties of this compound were given.In this paper we report the strongly enhanced binding properties of cyclodextrins modified with a calix [4]arene moiety at the secondary face. In these host molecules the upper rim of calixC41arene6 is facing via a xylyl spacer group to the wider opening of the cyclodextrin cavity. This arrangement can provide additional hydrophobic interaction and solvent shielding of a guest molecule accommodated in the cyclodextrin cavity. Binding interactions of the C-H hydrogens of organic guests with the n-arene system of calixarenes have been reported.7 The host molecules 1 and 2 were prepared by reaction of the secondary hydroxy face of heptakis(6-0-tert-butyldimethylsilyl) f3-cyclodextrin with a-bromotolunitrile, methylation of the remaining C(2)-hydroxys, conversion of the cyan0 group to the aminomethyl group, and reductive coupling with formylcalix[4]arene followed by desilylation.8The complexation behaviour of these water-soluble cyclodextrin-calixE41arene host molecules was studied with the fluorescent guests I -anilino-8-naphthalenesulfonate (ANS) and 2-p-toluidino-6-naphthalenesulfonate (TNS).l79 The fluorescence emission maximum of ANS in pH 7.0 buffered aqueous solution &,,,a, = 528 nm) shows a distinct blue shift and an increase in fluorescence intensity upon addition of fi-cyclodextrin to the solution (h,,,,,, = 508 nm). Both effects are indicat...

Abstract. 3-Aryl-3-azido-2-hydroxypropanoic esters, prepared from the corresponding 3-aryloxirane-2-carboxylic esters by ring opening with sodium azide, were reduced with tin( 11) chloride dihydrate in methanol to give 3-amino-3-aryl-2-hydroxypropanoic esters in good yields. Under these conditions, halogen substituents in the aromatic rings were not affected. The nitro group, however, was partially reduced to the amino group. Treatment of aliphatic oxirane-2-carboxylic esters with acetonitrile in the presence of boron trifluoride etherate led to regiospecific formation of 2,4-dialkyl-2-oxazoline-5-carboxylic esters, resulting from reaction of the nitrile at C3. Acidic hydrolysis of these oxazoline-5-carboxylic esters gave the corresponding 3-(acylamino)-2-hydroxy carboxylic esters. With these two complementary methods, both aryl-and alkyl-substituted 0-amino r-hydroxy acid derivatives are accessible.I n recent publications', we have reported the synthesis of aziridine-2-carboxylic esters from the corresponding oxirane-2-carboxylic esters (Scheme I). The first step in this synthesis involves ring opening of the epoxide function inScheme I substrate 1 with azide ion. The azido alcohols obtained in this manner are subsequently treated with triphenylphosphine to accomplish ring closure to the aziridines 4. The regiochemistry of the ring-opening reaction is strongly dependent on the nature of the R substituent. For the synthesis of the aziridines 4, this does not cause a problem, because both regioisomers 2 and 3 are converted into the same product. These aziridine-2-carboxylic esters can be used as starting materials for the preparation of a variety of P-substituted a-amino acid derivatives*.In those cases where the azide reaction with epoxy esters 1 proceeds regiospecifically, the azido alcohols can serve as potential starting materials for the corresponding amino alcohols. As demonstrated previously', aryl-substituted oxiranecarboxylic esters 1 exclusively yield azido hydroxy esters of type 2. It is, therefore, of interest to investigate the preparation of 0-amino 2-hydroxy carboxylic esters from azido alcohols 2 where R is an aromatic substituent'. For this purpose, a series of 3-aryl-3-azido-2-hydroxypropanoic esters 2 was prepared from the corresponding oxiranecarboxylic esters 1 in the manner described earlier'. For the conversion of an azide function into an amino group, several methods have been reported', e.g., reduction with hydrides, with phosphines, with sulfur derivatives and with low-valence metal ions, as well as catalytic hydrogenolysis. Most of these methods have serious drawbacks in the present case of the reduction of 2 (R = Ar), because of the presence of the hydroxyl and ester functions. Lithium aluminum hydride' will reduce the ester function, whereas sodium borohydride'",' is too weak a reducting agent for an azide. When the latter reduction is carried out under conditions of phase-transfer catalysis, conversion to amine can be achieved; however, the methyl ester function will then also be affe...