ABSTRACT
Pregnane glycoside P57, the appetite suppressant component from Hoodia, was synthesized expeditiously, featuring preparation of the aglycone Hoodigogenin A from digoxin and assembly of the deoxytrisaccharide with glycosyl o-alkynylbenzoates as donors.
Subject(s)
Apocynaceae/chemistry , Appetite Depressants/chemical synthesis , Plant Extracts/chemical synthesis , Saponins/chemical synthesis , Appetite Depressants/chemistry , Plant Extracts/chemistry , Saponins/chemistryABSTRACT
Digitoxin, a clinically important cardiac trisaccharide, was assembled efficiently from digitoxigenin and 3,4-di-O-tert-butyldiphenylsilyl-d-digitoxosyl o-cyclopropylethynylbenzoate in 9 steps and 52% overall yield via alternate glycosylation and protecting group manipulation. The present synthesis showcases the advantage of the gold(I)-catalyzed glycosylation protocol in the synthesis of glycoconjugates containing acid-labile 2-deoxysugar linkages.
Subject(s)
Benzoates/chemistry , Digitoxin/chemical synthesis , Glycosides/chemistry , Gold/chemistry , Catalysis , Digitoxin/chemistry , Molecular ConformationABSTRACT
A synthetic method of introducing bulky aryl groups at the 2-O- and 6-O-positions on glucopyranosides was developed. A total of 37 new compounds of this class were obtained successfully. These compounds were tested on several tumor cell lines by MTT assays, and some of them exhibited encouraging inhibitory activities. The most potent compound, CAB-SHZH-27, exhibited EC(50) values of 14, 12, and 10 micromol/L on A549, MDA-MB-231 and HeLa cells, respectively. A preliminary structure-activity relationship analysis indicates that the two free hydroxyl groups on the D-glucose core are indispensable for the biological activities of this class of compounds, and the aryl group at the 6-O-position has a more obvious impact than the one at the 2-O-position. An interesting 'on-off' mechanism of this class of compounds was also observed in our MTT assays, which remains to be explored.
Subject(s)
Antineoplastic Agents/chemical synthesis , Glucosides/chemistry , Glucosides/chemical synthesis , Neoplasms/drug therapy , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Drug Screening Assays, Antitumor , Glucosides/pharmacology , Glucosides/therapeutic use , HeLa Cells , Humans , Structure-Activity RelationshipABSTRACT
The title compound, C(21)H(34)O(4), is a steriod of the pregnane family prepared by the sequential oxidation and reduction of 3ß,12ß-diacet-oxy-20-ethyl-enedioxy-pregnan-14-ene. The con-formations of the six-membered rings are close to chair forms, while the five-membered ring adopts an envelope conformation. All the rings are trans-fused and an intra-molecular O-Hâ¯O hydrogen bond occurs. In the crystal structure, inter-molecular O-Hâ¯O hydrogen bonds link the mol-ecules into a two-dimensional network.
