• Home
  • Search Results
  • A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products.

A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products.

Nature chemistry (2013-02-21)
Robert W Huigens, Karen C Morrison, Robert W Hicklin, Timothy A Flood, Michelle F Richter, Paul J Hergenrother
ABSTRACT

High-throughput screening is the dominant method used to identify lead compounds in drug discovery. As such, the makeup of screening libraries largely dictates the biological targets that can be modulated and the therapeutics that can be developed. Unfortunately, most compound-screening collections consist principally of planar molecules with little structural or stereochemical complexity, compounds that do not offer the arrangement of chemical functionality necessary for the modulation of many drug targets. Here we describe a novel, general and facile strategy for the creation of diverse compounds with high structural and stereochemical complexity using readily available natural products as synthetic starting points. We show through the evaluation of chemical properties (which include fraction of sp(3) carbons, ClogP and the number of stereogenic centres) that these compounds are significantly more complex and diverse than those in standard screening collections, and we give guidelines for the application of this strategy to any suitable natural product.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Gibberellic acid, BioReagent, suitable for plant cell culture, ≥90% gibberellin A3 basis (of total gibberellins.)
Sigma-Aldrich
Gibberellic acid, 90% gibberellin A3 basis (HPLC)
Sigma-Aldrich
Quinine, suitable for fluorescence, anhydrous, ≥98.0% (dried material, NT)
Sigma-Aldrich
Quinine, 90%
Supelco
Gibberellic acid, PESTANAL®, analytical standard
Supelco
Quinine, certified reference material, TraceCERT®
Sigma-Aldrich
Gibberellic acid potassium salt, suitable for plant cell culture, BioReagent, ~95%, ≥50% total GA3 basis
Sigma-Aldrich
Adrenosterone, 98%