Pathway development and pilot library realization in diversity-oriented synthesis: exploring Ferrier and Pauson-Khand reactions on a glycal template

Chem Biol. 2002 Feb;9(2):265-76. doi: 10.1016/s1074-5521(02)00099-6.

Abstract

Through a correlation of the ability of small molecules to bind biological macromolecules and their ability to modulate cellular and organismal processes, chemistry can inform biology and vice versa. Diversity-oriented organic synthesis (DOS), which aims to provide structurally complex and diverse small molecules efficiently, can play a key role in such chemical genetic studies. Here we illustrate the trial-and-error experimentation that can refine an initial pathway-planning exercise and result eventually in an effective diversity pathway. By exploring Ferrier and Pauson-Khand reactions on a glycal template, we have developed efficient and stereoselective syntheses of tricyclic compounds. In this pathway, diversity results from the substituents and their spatial relationships about the tricyclic rings. A pilot split-pool library synthesis of 2500 tricyclic compounds highlights the use of planning considerations in DOS and a "one-bead, one-stock solution" technology platform. Additionally, it illustrates a promising synthetic pathway for future chemical genetic studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbohydrates / chemical synthesis*
  • Carbohydrates / chemistry*
  • Combinatorial Chemistry Techniques / methods*
  • Heterocyclic Compounds, 3-Ring / chemical synthesis*
  • Heterocyclic Compounds, 3-Ring / chemistry*
  • Stereoisomerism
  • Templates, Genetic

Substances

  • Carbohydrates
  • Heterocyclic Compounds, 3-Ring