Synthesis, Structure, and Biological Activity of Ferrocenyl Carbohydrate Conjugates

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• 作者：Cara L. Ferreira ; Charles B. Ewart ; Cheri A. Barta ; Susan Little ; Vanessa Yardley ; Candice Martins ; Elena Polishchuk ; Peter J. Smith ; John R. Moss ; Michael Merkel ; Michael J. Adam ; Chris Orvig
• 刊名：Inorganic Chemistry
• 出版年：2006
• 出版时间：October 2, 2006
• 年：2006
• 卷：45
• 期：20
• 页码：8414 - 8422
• 全文大小：237K
• 年卷期：v.45,no.20(October 2, 2006)
• ISSN：1520-510X

文摘

Seven ferrocenyl carbohydrate conjugates were synthesized. Coupling reactions of monosaccharide derivativeswith ferrocene carbonyl chloride produced {6-N-(methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy--D-glucopyranoside)}-1-ferrocene carboxamide (3), {1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1-ferrocene carboxylate (4), and {6-O-(1,2,3,4-tetra-O-acetyl--D-glucopyranose)}-1-ferrocene carboxylate (5). Similarly, 1,1'-bis(carbonyl chloride)ferrocene was coupled with the appropriate sugars to produce the disubstituted analogues bis{6-N-(methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy--D-glucopyranoside)}-1,1'-ferrocene carboxamide (8), bis{1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1,1'-ferrocene carboxylate (9), and bis{6-O-(1,2,3,4-tetra-O-acetyl--D-glucopyranose)}-1,1'-ferrocene carboxylate (10). {6-N-(Methyl-6-amino-6-deoxy--D-glucopyranoside)}-1-ferrocene carboxamide monohydrate(12) was synthesized via amide coupling of an activated ferrocenyl ester with the corresponding carbohydrate. Allcompounds were characterized by elemental analysis, ¹H NMR spectroscopy, and mass spectrometry. X-raycrystallography confirmed the solid-state structure of three ferrocenyl carbohydrate conjugates: 2-N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-D-glucopyranose)-1-ferrocene carboxamide (1), 1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D-glucopyranose)-1-ferrocene carboxylate (2), and 12. The above compounds, along with bis{2-N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-D-glucopyranose)}-1,1'-ferrocene carboxamide (6), bis{1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D-glucopyranose)}-1,1'-ferrocene carboxylate (7), and 2-N-(2-amino-2-deoxy-D-glucopyranose)-1-ferrocenecarboxamide (11) were examined for cytotoxicity in cell lines (L1210 and HTB-129) and for antimalarial activity inPlasmodium falciparum strains (D10, 3D7, and K1, a chloroquine-resistant strain). In general, the compounds werenontoxic in the human cell line tested (HTB-129), and compounds 4, 7, and 9 showed moderate antimalarialactivity in one or more of the P. falciparum strains.