Monoazide cyclodextrins

Cyclodextrins monoazide 14a-b can also be synthesized by direct substitution reaction, using triphenylphosphine, carbon tetrabromide, and Hthium azide in DMF, but the yields are modest [24]. 

Monoazide a- and p-cyclodextrins 77a-b were easily obtained from the corresponding monohydroxy cyclodextrins 63a-b. When submitted to DIBAL-H, the azide is reduced first. Aluminum derivatives complexed on the formed amide create steric hindrance, which directs the following de-O-benzylation toward the farthest position [74] (Scheme 9.36) as in the case of monohydroxy cyclodextrin 63a (Scheme 9.30 and Scheme 9.31). For a-cyclodextrin, the farthest position is 6D, which leads to the 6A-amino,6D-hydroxyl regioisomer 78a in 74% yield. For P-cyclodextrin, a molecular model study revealed that the farthest position is 6E, leading to the formation of the 6A-amino,6E-hydroxyl regioisomer 78b in 89% yield. It has to be noted that this pattern of differentiation is the same as for 6A-hydroxyl,6D-azido cyclodextrins 43a-b (Scheme 9.18). 

The same procedure can be used with a- or P-cyclodextrin monoazide 77a-b for the tandem reaction reduction of the azide and selective debenzylation on the opposite position [74],... 

Considerable progress has been made with the study of substituted derivatives. The L-histidyl-L-histidyl derivative (32), which is a potential enzyme mimic with two recognition sites, has been made from a 6-deoxy-6-iodo-/3-cyclodextrin. A somewhat related pair of substances, 6-N-(N -formyl- )- and L-phenylalanyl)-6-amino-6-deoxy-(3-cyclodextrin, were made from the 6-amino compound and their inclusion behaviour was studied. In similar work the 6-monoazide was partially methylated and reduced, and the amino product was coupled with both enantiomers of N-protected phenylalanine. Other workers have reported the fully O-methylated 6-azido-6-deoxy p-compound. ... 

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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