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An effective solid-phase preparation of the pharmaceutically interesting 4 H -2-(3-hydroxy-4-methoxyphenyl)-naphtho[1,2- b ]pyran-1-one system from an anchored bisarylacetylene is described.

[reaction: see text] Syntheses of 2-substituted furo[3,2-b]pyridines and furo[3,2-h]quinolines have been achieved for the first time in the solid-phase mode. The central enabling steps involved concomitant deprotection/cyclization promoted by the mild base K(2)CO(3). Reactions were monitored "in situ" in real time by a variety of spectroscopic techniques, which allowed full and accurate control of progress in these syntheses.

The efficacy, limitations and scope of different spectroscopic techniques to monitor solid-phase syntheses are discussed. The total solid-phase synthesis of a natural product derivative, 3,17-di-O-acetyllamellarin U, has been monitored by gel-phase NMR and HR-MAS NMR as appropriate. FT-IR and colorimetric tests also proved to be valuable tools for monitoring the progress of reactions. While the data obtained by FT-IR provided valuable information on some functional groups, the NMR data provided more specific structural information that allowed the progress of reactions to be monitored. After several reaction steps the "aging" of the resin only allowed the product covalently anchored to the resin to be investigated using an HR-MAS probe, a situation that severely limited the depth of analysis available.

[reaction: see text] A total solid-phase synthesis of lamellarins U and L has been achieved. The conversion of an aldehyde group into a formate by a Baeyer-Villiger reaction and a intramolecular [3 + 2] cycloaddition of a 3,4-dihydroisoquinolinium salt over a triple bond comprise the key steps of the process. Each transformation has been controlled with the proper spectroscopic and analytical methods.

The synthetic routes used for the preparation of marine alkaloids variolin B and lamellarins are described.

A convenient and easy method based on 1H NMR spectroscopy with both external and internal standards is described for the quantification of members of libraries.

Solid-phase chemistry, first introduced for peptide synthesis in the 1960's, has become an integral part of organic synthetic methodology. Presented herein is an overview of recent examples of the use of solid-phase in the preparation of non-peptidic natural products and related compounds, encompassing on-resin total syntheses as well as the use of polymer-supported reagents in solution.