Synthesis of macrocycles on the basis of diterpenoid isosteviol and trehalose

Last Step towards Macrocyclic Glycoterpenoids Having Isosteviol and Glucosamine Moieties

“…As the aglycon of target diglycosides as well as the diterpenoid component of future macrocyclic glycoterpenoids, diterpenoid diols 9, 10 and diterpenoid diacids 12, 13 were used. They were synthesized in 4 th and 5 th steps, respectively, by analogy with [7] (Scheme 2). At the first step, isosteviol 5 was converted to dihydroisosteviol 6 by treatment with sodium tetrahydridoborate, and two molecules of this isosteviol derivative were bonded by the reaction with suberoyl or sebacoyl chlorides afforded diterpenoid diacids 7 and 8 (Scheme 2).…”

“…One can see that the interaction of deprotected amino groups of glucosamine residues of diglycosides 14, 15, 18, 19 with bielectrophilic reagents will lead to their macrocyclization, and macrocyclic glycoterpenoids analogous to already known macrocycles [4][5][6][7] will be obtained. These reactions are currently being studied and will be reported soon.…”

“…Isosteviol 5, diterpenoid diols 10, 11, diterpenoid diacids 12, 13 were prepared according to the literature. [7,19] 3,4,6-Tri-О-acetyl-2-deoxy-2-[(2,2,2-trichloroethoxy)carbonylamino]-a-D-glucopyranosyl bromide 4 was prepared according to the literature. [20] The physicochemical properties of these compounds agreed with those published.…”

“…Recently the first syntheses of open chain and macrocyclic glycoterpenoids having one or several diterpenoid moieties bonded with various carbohydrate residues, namely D-glucopyranose [1,2] , glucuronic acid [3][4][5] or trehalose [6,7] have been reported. In continuation of these investigations 2-deoxy-2-amino-D-glucopyranose (glucosamine) was chosen as the next carbohydrate block for macrocyclic glycoterpenoids.…”

The First Macrocyclic Glycoterpenoid Having Glucosamine and Isosteviol Moieties

“…[1][2][3][4] It was found that these macrocycles inhibited the in vitro growth of H37Rv strain of M. Tuberculosis at the minimal inhibition concentration (MIC) value of 12.5 mg/mL that is comparable to the activity of antitubercular drug pyrazinamide. [3,4] Herein, the synthesis of the first macrocyclic glycoterpenoid having isosteviol and glucosamine residues is reported. We followed the previously proposed approach [1] according to which the terminal reactive groups of binuclear isosteviol derivative are functionalized with carbohydrate residues, and these ones then are coupled by any linker.…”