Transformation of D-(-)-ribose into a natural product-like scaffold via a Lewis acid catalyzed intramolecular hetero-Diels-Alder reaction.

Starting from D-(-)-ribose, a tricyclic natural product-like scaffold suitable for combinatorial derivatization was synthesized via an intramolecular hetero-Diels-Alder reaction. Lithium perchlorate was found to enhance the reaction rate and, at the same time, had a pronounced influence on the chemoselectivity of the reaction. The stereochemical course of the reaction, however, was not influenced by the Lewis acid.

Natural product-like libraries based on non-aromatic, polycyclic motifs.

Diversity-oriented synthesis is an intriguing approach for creating structurally diverse compounds that cover the pharmaceutically relevant chemical space in an optimal way. On the other hand, an over-proportionally large number of drugs or lead structures originate from compounds isolated from natural sources. Thus, not surprisingly, an increasing number of combinatorial libraries are based on motifs resembling natural products.

Elaboration of D-(-)-ribose into a tricyclic, natural product-like scaffold.

The construction of natural product-like, tricyclic compounds is reported. Starting from a D-(-)-ribose-derived dihydrofurane, the tricyclic scaffold is prepared via an intramolecular hetero-Diels-Alder reaction. The reaction proceeds with very high diastereoselectivity through an endo transition state, as established on the basis of X-ray structural analysis of the products.