Tosyl-cyclodextrin synthesis

The synthesis of the bis-P-cyclodextrin 35 is outlined in Fig. 14. Interestingly, however, the X-ray structure of 36, the de-tosylated 35, revealed that P-carotene would not be incorporated into both CD units due to the unfavorable orientation of the diamide linker which blocks the entrance to the second P-CD. In agreement with this result are experiments with the target Ru complex 37 which displayed central cleavage on P-carotene 1 5delding retinal 2 as the major product (Fig. 15) (19). 

Since tosyl group and bromide have the same efficiency as leaving groups, the synthesis in good yield of heptakis-6-thioglycosyl- cyclodextrin (17 e, 17f) from the heptakis(6-bromo-6-deoxy)- cyclodextrin (15c) needs, as expected, the sodium salts of 1-thiogalactose (16c, 16d) and high temperature (Scheme 6) [27]. 

The synthesis given here is based on Bittman s route to monotosylated /3-cyclodextrin (20) [8] which in turn provides a basis for many monosubstituted cyclodextrin derivatives. Formation of the product is easy to determine because, despite the complex 1H NMR spectrum that results, the signals due to the tosylate group are very distinct. Another useful derivative, though not included here, is the aldehyde which can be prepared directly from /3-cyclodextrin or its monotosylated derivative [9,10], as illustrated in Figure 2.18. 

We devised a method to perform the selective tosylation of the C-2 hydroxyl group in )3-cyclodextrin, and used it to attach the pyridoxamine to this secondary side of the cyclodextrin. Again we saw some preference for transamination of the aromatic ketoac-ids, but by less than we had observed with the pyridoxamine attached to C-6. The tryptophan synthesis was only 25 times as fast as that for alanine, while the phenylalanine formation was 18 times as fast as alanine in competitive reactions. Modest enantioselec-tivities were observed as well with this C-2 linked pyridoxamine, and they differed in detail from those produced with the C-6 isomer that we had reported earlier. 

Recently, the synthesis of the heptasilylated p-cyclodextrin 4 has been reported [4]. This compound, which is soluble in organic solvents, can be monotosylated at the secondary side in 30 % yield by reaction with one equivalent of NaH in tetrahydrofuran and treatment with p-tosyl chloride (Scheme 1). Subsequent epoxidation and ringopening with UN3 afforded in good yield the monoazide 5, which, after reduction, can be used in coupling reactions with other building blocks [5]. 

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