Synthesis of Nitrogen‐ and Oxygen‐Containing Macrocycles—Derivatives of Lithocholic Acid

Abstract

Palladium-catalyzed amination of 3,24-bis(3-bromophenoxy)cholane (4) with various polyamines and polyoxadiamines 5 taken in 1:1 ratio was used for the synthesis of the macrocycles 6, which contain steroidal and polyamine moieties and were obtained in 38-65 % yields. The same reaction with excess polyamine (2.2-3 equiv) provided bis(polyamino) derivatives of 3,24-diphenoxycholane 7 in excellent yields, whereas the diarylation of polyamines with two equivalents of 3,24-bis(3-bromophenoxy)cholane afforded their bis(steroidal) derivatives 8. Compounds 7 and 8 were employed in the syntheses of cyclodimers 9, which possess two steroidal and two polyamine fragments; the efficiency of two methods was compared.

Palladium-catalyzed amination in the synthesis of polyazamacrocycles

“…ular sensors for chiral organic molecules. Initial 3,24-bis(haloaryloxy)cholanes were synthesized in high yield from cholane-3,24-diol by the Mitsunobu reaction, and the aromatic fragments therein were derived from 1,3-disubstituted benzene [118,119], 2,6-disubstituted pyridine [120,121], and 2,8-disubstituted quinoline [122]. The results of palladiumcatalyzed amination strongly depended on the nature of the aromatic fragment.…”

Biomaterials made of bile acids

“…Cyclocholates and cholaphanes are two major kinds of such cyclic molecules (Figure 12) [13] . Cyclocholates are macrocyclic polyesters with two to six bile acid units formed by head-to-tail cyclization [78] , and cholaphanes are macrocycles consist of two to four bile acid units joined together by different spacer groups [79][80][81] . Cholaphanes attract more attention because their properties can be tuned by the spacer groups.…”

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

“…[7–8 25–27]. Later, two modern synthetic approaches based on metal-catalyzed reactions were applied for the modification of bile acids – cross-coupling [28–29] (Scheme 1) and Cu(I)-catalyzed cycloaddition of azides to alkynes (Fig. 1) [11,16,30–32].…”

“…Though this method is often preferable for the macrocyclization in comparison to classical nucleophilic substitution [28,31], it is limited to bile acid derivatives bearing groups with C(sp 2 )–Hal bonds. In addition, the use of bile acid moieties saturated with hydroxy groups was inconvenient for the syntheses of bis(polyoxamino) derivatives by Pd-catalyzed amination [34–35].…”