Chiral macrocyclic polyethers

With Secondaiy and Tertiary Amine Functions in Chiral Macrocyclic Polyether Rings. 264... 

With Fused Pyridino Rings in Chiral Macrocyclic Polyethers. 270... 

The chiral dimethyl derivatives RR)-M and (SS)-84 of tetraethylene glycol have been employed (126) in the preparation of chiral macrocyclic polyether diesters such as (JU )-85 and (SS)S6. The reactions of the chiral diols with the appropriate diacid chlorides generally proceed (Scheme S) in good yield in warm benzene under high dilution conditions. 

Nitrogen atoms have been incorporated into chiral macrocyclic polyethers in a variety of different ways. One of the most straightforward approaches is the... 

The pyridine subcycle unit has been introduced into a wide range of 18-crown-6 derivatives. For example, reaction of 2,6-pyridinedicarbonyl chloride with the dimethyl substituted tetraethylene glycol (SS)-84, derived from (S)-lactic acid, afforded (126) the chiral macrocyclic polyether diester (5S)-184. A similar preparative approach (127) gave (SS)-185, where the source of the chirality is (5)-mandelic acid. 

Fig. 66. a, Structure of a chiral macrocyclic polyether b, cross section of a, viewed along axis of naphthalene-naphthalene bond from under side... 

The previous section demonstrated that chiral macrocyclic polyether hosts discriminate in complexation reactions in chloroform solution between enantiomers of amino ester salt guests. With these results can we go one step further and mimic a catalytic site We will now describe the design of a host that upon complexation with a-amino ester salts produces a transition state intermediate corresponding to a transacylation (thiolysis) reaction between the chiral host catalytic group (thiol) and the enantiomeric guest salts (143). However, it should immediately be realized that these model systems mimic only the acylation step encountered in serine protease catalysis. So far no acceleration in rate has been observed for the deacylation step. 

The chiral macrocyclic polyether (U)-d-(521) and its (5)-D-diastereoisomer have been derived from D-mannitol and (R)- or (S )-binaphthol, respectively. Significant changes were observed in the n.m.r. spectra of (/ )-d-(521) and its diastereoisomer in the presence of primary alkylammonium salts [e.g. (+)-(2 )-, (-)-(5 )- and ( )-(i 5 )-a-phenylethylammonium hexafluorophos-phate], indicating that both diastereoisomers act as hosts to suitable guest molecules. The chiral hosts dd-(523) and dd-(524) have been obtained from l,2 5,6-di-0-isopropylidene-D-mannitol by the routes outlined in Scheme 100. The temperature dependence of the H n.m.r. spectrum of the 1 1 complex of dd-(524) and benzylammonium thiocyanate in [ Ha]dichloromethane was interpreted... 

Crown-ethers are macrocyclic polyethers capable of forming host-guest complexes, especially with inorganic and organic cations. Modification of the crown-ether by the introduction of four carboxylic groups makes it possible to use this class of compounds as chiral selectors in CE. ... 

A number of chiral crown compounds containing more than one macrocyclic polyether ring have been described in the literature. They have been derived... 

Chirality derived from the readily accessible a-amino acids has been incorporated into the side chains of aza and diaza macrocyclic polyethers. A number of procedures suitable for peptide synthesis have proved (178) to be unsuitable for acylating the relatively unreactive secondary amine groups of aza crown ethers. Eventually, it was discovered that mixed anhydrides of diphenylphos-phinic acid and alkoxycarbonyl-L-alanine derivatives do yield amides, which can be reduced to the corresponding amines, e.g., l-172. By contrast, the corresponding bisamides of diaza-15-crown-S derivatives could not be reduced and so an alternative approach, involving the use of chiral A-chloroacetamido alcohols derived from a-amino acids, has been employed (178) in the synthesis of chiral receptors, such as ll-173 to ll-175, based on this constitution. 

The reaction sequence outlined in Scheme 12 illustrates how macrocyclic polyether-thiono diesters such as RR)-lfi6 can be prepared (184) from 0,0-dimethyl 2,6-pyridinedicaibothiolate and (RR)-S4, Potassium thiocyanate forms a 1 1 crystalline complex with (RR)-1S6 and presumably the potassium ion serves as a template for the (1 -I-1) cyclization. Raney nickel desulfurization of (/ R)-186 yields the chiral pyridino-18-crown-6 derivative RR)-191. 

Finally, the chiral macrocyclic peracetylated polyhydroxy polyethers (+)-201 and (+)-202 have been prepared (194) recently by treatment of a- and 0-cyclodextrins, respectively, with diethylborane and 9-borabicyclo[3.3.1]nonan-9-yl methanesulfonate as catalyst. 

Also, the structure of 63 is better described as zwitterionic with a C-N bond length of only 1.651 A <2001J(P2)133> in the case of methoxy instead of NMe2, the MeO- C=S separation is longer (2.550 A) and the two substituents behave as normal /rm-substituents. Furthermore, the 2,6,9-trioxo-bicyclo[3,3,l]nona-3,7-diene moiety 64 has been structurally characterized as part of Pd(ii) complexes <2003JOM(676)93> and as a novel chiral spacer unit in macrocyclic polyethers <2002SMC383, 2004T2857>. 

A great variety of macrocyclic polyethers have been shown to bind R-NH3+ molecules with structural and chiral selectivity [2.100-2.103, 2.107]. Extensive... 

Crown ethers are syntheHc macrocyclic polyethers that can form selective complexes with various cations. Anl8-crown-6 ether is illustrated in Fig. 8, where 18 indicates the total number of atoms in the polyether ring and 6 the number of oxygen atoms. Chiral crown ethers have been synthesized by... 

The ability of crown polyethers to form complexes with ammonium and alkylammonium salts") gave rise to the development of Cram s concept of host-guest chemistry57). Asymmetric macrocyclic polyethers (host molecules) were designed and synthesized that distinguish between the enantiomers of chiral amine salts (guest molecules). For example, the (R,Reform of polyether (Fig. 66) which was obtained in pure state, forms complexes of different... 

Aromatic templates, in conjunction with coordinative bonds, have been employed by Sanders et al. [42] to self-assemble a [2]catenane incorporating a chiral metallomacro-cycle. The 1,5-dioxynaphthalene-based macrocyclic polyether 60 threads onto the r-elec-tron-deficient compound 61 in MeCN. Thus, when both compounds and Zn(OS02CF3)2 are mixed in this solvent, threading of 60 onto 61 is followed by the [2 + 2] assembly of a helical metallomacrocycle as a result of the tetrahedral coordination of two Zn centers by the bipyridine ligands appended to the r-electron-deficient recognition sites. The resulting [2]catenane 62 was characterized by a combination of H-NMR spectroscopy and electrospray mass spectrometry. 

An established area of application of macrocyclic polyethers is the stereoselective complexation of chiral guest primary alkylammonium salts by optically active host macrocycles. Full details of the resolution, optical stability, and inclusion into chiral hosts of the binaphthol (84), and also of the chiral recognition properties of crowns [e.g. (85)] based on simple carbohydrate precursors, have been reported this year. An extension of the latter work" utilizes derivatives of the more complex carbohydrates D-glucose and D-galactose. The macrobicyclic polyethers (86) derived from D-glycerol or pentaerythritol have been suggested as potential chiral (at the bridgeheads) cryptands. 

Crown ethers are synthetic macrocyclic polyethers that can form selective complexes with various cations. Chiral crown ethers such as (diphenyl-substituted l,l -binaphthyl) crown ether or (-Fill 8-crown-6)-2,3,11,12-tetracarboxylic acid, which are bound to silica gels or coated on reversed-phase materials, were utilized for the enantioseparation of underivatized primary amino acids and their esters. On the other hand, the enantiomers of underivatized and derivatized amino acids enter into... 

Baba N, Oda J, Inouye Y (1982) Abhangigkeit der Enantioselektivitat von der relativen Konzentration des Substrats bei einer NADH--Modellreaktion. Angew Chem 94 465-466 Baba N, Oda J, Inouye Y (1983) Addition effect of some macrocyclic polyethers on the asymmetric reduction with chiral NADH model compounds. Bull Inst Chem Res Kyoto Univ 61 113-116 Baba N, Amano M, Oda J, Inouye Y (1984) Asymmetric reduction with chiral NADH model compounds A dynamic aspect of product stereochemistry. J Am Chem Soc 106 1481-1486 Bally C, Leuthardt F (1970) Die Stereospezifitat der Alkoholdehydro-... 

Cram and co-workers have continued their elegant work on host-guest com-plexation and particularly on chiral recognition in solution. The syntheses of a large number of stereoisomeric macrocyclic polyethers that contain chiral units have been described. The general shape is as shown, (10), giving a chiral cavity. They have been used for optical resolution of racemic alkyl ammonium salts and the catalytic reduction of enantiomers. ... 

Chiral crown ethers are synthetic macrocyclic polyethers and were first introduced as CSPs for LC by Cram and co-workers in the late 1970s. In their pioneer works, bis-(l,r-binaphthyl)-22-crown-6 was immobilized on silica gel [126] or polystyrene [127] to resolve a-amino acids and their derivatives. Since then, different chiral crown ether CSPs have been developed and successfully applied in the HPLC separation of enantiomers containing primary amine and secondary amine groups [20, 128-139]. Both dynamically coated [128, 129] and covalently bonded [130-132] chiral crown ether CSPs are commercially available. 

One of the most recently reported CCC chiral separations where chiral recognition occurs in the aqueous phase involves the separation of gemifloxacin enantiomers using (-(-)-(18-crown-6)-tetracarboxylic acid (I8C6H4) as CS [37]. This CS has been previously used in CE to resolve the enantiomers of chiral primary amines. The macrocyclic polyether ring in ISCeHq structure forms stable inclusion complexes with protonated primary amines. This interaction is the basis of the chiral recognition mechanism. 

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