Solid-Support Synthesis of Natural Product-like Compounds Derived from d-(-)-Ribose

Abstract

The synthesis of natural product-like compounds on ­solid support is described. Starting from a readily accessible d-(-)-ribose derivative, a tricyclic scaffold is prepared in five steps. After coupling onto solid supports bearing different substituents (PAL resins), the scaffold can be further derivatised at two diversity points. Representative derivatives obtained by this diversity-oriented procedure are described.

Key words

solid-phase synthesis - hetero Diels-Alder reactions - medicinal chemistry - combinatorial - furans

References

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8

Other conditions and different coupling reagents were tried but did not result in an improvement of the yields.

9

In a preliminary experiment, the yield could be improved using different conditions. Thus, the use of lithium perchlorate (1.5 M) in MeCN as a catalyst allowed cyclisation of 5a at a temperature of 50 °C in 50 h. Compound 6a was isolated in a 55% yield. Further experiments in this direction are ongoing.

11

HCTU: N-[(1H-6-chlorobenzotriazol-1-yl)(dimethyl-amino)methylene]-N-methylmethanaminium hexafluoro-phosphate N-oxide.