Synthesis and biological evaluation of enantiomeric rhamnose analogues of the antitumour agent spicamycin - is the mode of action by modification of N-linked glycoproteins?

Journal article

The synthesis of both enantiomers of dodecyl rhamnospicamycin 2a and 2b, a rhamnose analogue of the naturally occurring combinatorial library spicamycin 1, are derived from L-rhamnose and methyl α-D-mannopyranoside, respectively. The L-(+)-enantiomer 2a containing an L-rhamnose fragment is shown to be highly cytotoxic towards human myeloma cells with an IC50=120 nM, whereas the D-(-)-enantiomer 2b, based on a D-mannose structure, shows no significant cytotoxicity. The analogue 16, in which the nucleotide base fragment has been replaced by a simple methoxy group, has no cytotoxicity. Initial studies towards clarifying the mechanism of anti-cancer action of spicamycin analogues are reported.

Authors: Martin, A; Butters, T; Fleet, G

• Publication status: Published
• Journal: TETRAHEDRON-ASYMMETRY
• Volume: 10
• Issue: 12
• Pages: 2343-2360
• Publication date: 1999-06-18
• DOI: 10.1016/S0957-4166(99)00240-2
• ISSN: 0957-4166
• Language: English