Contiguous Stereogenic Quaternary Carbons: A Daunting Challenge in Natural Products Synthesis

Abstract

One element of structure that invariably increases the difficulty of a chemical synthesis is the presence in the target molecule of contiguous all-carbon quaternary stereocenters. This Perspective will examine the most useful transformations and strategies devised recently for directly assembling this structural unit.

Drug discovery from medicinal plants

“…Combining these categories, research on natural products accounts for approximately 48% of the NCEs reported from 1981-2002. Natural products provide a starting point for new synthetic compounds, with diverse structures and often with multiple stereocenters that can be challenging synthetically (Clardy and Walsh, 2004;Nicolaou and Snyder, 2004;Peterson and Overman, 2004;Koehn and Carter, 2005). Many structural features common to natural products (e.g., chiral centers, aromatic rings, complex ring systems, degree of molecule saturation, and number and ratio of heteroatoms) have been shown to be highly relevant to drug discovery efforts (Lee and Schneider, 2001;Feher and Schmidt, 2003;Clardy and Walsh, 2004;Piggott and Karuso, 2004;Koehn and Carter, 2005).…”

Asymmetric Allylation of α‐Ketoester‐Derived N‐Benzoylhydrazones Promoted by Chiral Sulfoxides/N‐Oxides Lewis Bases: Highly Enantioselective Synthesis of Quaternary α‐Substituted α‐Allyl‐α‐Amino Acids

“…On the other hand, the stereoselective formation of chiral quaternary centers remains a challenging subject in asymmetric synthesis; thus, we deemed it of interest to examine the applicability of chiral bis‐sulfoxide/ N ‐oxide ( R , R )‐ 2 in the enantioselective allylation of hydrazones derived from α‐keto esters. If successful, this protocol will create a new quaternary center in the product, which can be derivatized to biologically active α‐allyl α‐amino acids (Scheme ) …”