Synthesis of a Cycloallin Derivative from β‐Cyclodextrin: Heptakis(2,3‐dideoxy‐2,3‐epithio)‐β‐cycloallin

Abstract

Macrocyclic molecules that comprise several subunits in a circular array exhibit novel functions that are otherwise not observed in the individual units. Many host molecules that consist of several identical functional subunits, such as cyclodextrins, cyclophanes, and their related natural and artificial macrocycles, have been prepared by enzymatic or synthetic methods and have developed the concept of artificial molecular recognition and catalysis.[1] Cyclodextrins, in particular, have been the leading compounds from the initial stage of this research. Despite extensive studies on the functionalization of cyclodextrins for diverse purposes such as the development of artificial receptors and enzymes, their modification has been limited mostly to their primary hydroxy groups while secondary sites have received much less attention.[2] Moreover, successful studies on complete modifications at the secondary sites are rare as the modifications on 2-OH or 3-OH do not proceed selectively and are accompanied inevitably by products of either over-or undermodification. Only per(3,6-anhydro)- [3] and per(2-O-tosyl)-cyclodextrins, [4] per(2,3-anhydro)-cyclomannins 1 (see Scheme 1), [4,5] cycloaltrins, [6] per(3-amino-3-deoxy)-b-cycloaltrin, [7] and per(3-deoxy)-cyclomannins [8] are available by the selective modifications of cyclodextrins at the present time. However, to the best of our knowledge, the preparation of a cycloallin family has not been studied as yet.Here, we report the first successful one-pot preparation of a novel type of cycloallin derivative, 2, from cyclomannin derivative 1, which itself is obtained in three steps from bcyclodextrin (Scheme 1). The synthesis is as simple as heating an aqueous acidic solution of 1 at 90 8C for 30 min followed by stirring at room temperature under alkaline conditions. It is quite astonishing that these simple reaction conditions not only ensure a complete conversion of the seven epoxide

Selective modification of β-cyclodextrin: an unexpected tandem reaction enables the cross-linking of C2A and C2B via a sulfur atom

“…Table 1 for the structural data). 5 { When treated by 1 M NaOH at 70 uC, 3 underwent a very clean reaction, affording a pure product in 73% yield. { However, the structural assignment revealed that this product takes the structure of 5 rather than the expected 4!…”

Shortcut Synthesis of β-Cyclomannin from β-Cyclodextrin

“…Thus, effective and stereoselective transformations of all glucoside units to other sugar units gave non-glucose cyclooligosaccharides: per(3,6-anhydro)-CDs, per(2,3-anhydro)-cyclomannins, cycloaltrins, per(3-amino-3-deoxy)-β-cycloaltrin, and per(3-deoxy)-cyclomannins . Recently, we added per(2,3-dideoxy-2,3-epithio)-β-cycloallin and per(2,3-didehydroxy)-β-CD 2 as new members to this family …”

“…The CD-based methodology for the synthesis of 3 is depicted in Scheme . A five-step transformation of β-CD 1 afforded the olefin 2 , and the latter was treated with OsO 4 / N -methylmorphorin- N -oxide in water to give cyclomannin 3 in 64% yield . This synthetic process is dramatically short compared with the literature one .…”