Diversity-oriented synthesis

Diversity-oriented synthesis aims to produce chemical libraries that are representative of a large portion of chemical space by applying a variety of reaction conditions to starting materials with multiple different functional groups. Multiple rounds of such reactions result in rapid access to structurally diverse products suitable for screening.

Latest Research and Reviews

  • Research | | open

    Diversity-oriented synthesis is a valuable strategy to construct complex molecules of medicinal interest. Here, the authors show a folding cascade strategy to convert linear substrates into polycyclic compounds with multiple stereocentres by combining the reductive chemistry of SmI2 with 1,5-hydrogen atom transfer.

    • Mateusz P. Plesniak
    • , Monserrat H. Garduño-Castro
    • , Philipp Lenz
    • , Xavier Just-Baringo
    •  & David J. Procter
  • Research | | open

    Non-covalent glycosyl donor activation often requires high organocatalyst loadings. Here, the authors demonstrate that strain-release glycosylations can take place at very low thiourea catalyst loadings. In addition, the authors developed a one-pot multicatalytic strategy that can diversify glycosides rapidly.

    • Chunfa Xu
    •  & Charles C. J. Loh
  • Research | | open

    Development of comprehensive structure–activity relationships for coronatine has been a major goal in the agrochemical industry. Here, the authors report the gram-scale production and structure–activity relationship of parent coronafacic acid and ultimately rationalise the biological activity of analogues of this phytotoxin.

    • Mairi M. Littleson
    • , Christopher M. Baker
    • , Anne J. Dalençon
    • , Elizabeth C. Frye
    • , Craig Jamieson
    • , Alan R. Kennedy
    • , Kenneth B. Ling
    • , Matthew M. McLachlan
    • , Mark G. Montgomery
    • , Claire J. Russell
    •  & Allan J. B. Watson
  • Research | | open

    Late-stage diversification of natural products is an important starting point for drug discovery. Here, the authors use chiral reagents to perform the regiocontrolled ring expansion of steroid precursors and achieve more than 100 isomerically pure analogs with spatial and functional diversity.

    • Manwika Charaschanya
    •  & Jeffrey Aubé
  • Research |

    The biomimetic syntheses of bipleiophylline, one of the most complex monoterpene indole alkaloids, and voacalgine A, its biosynthetic precursor, have been achieved from pleiocarpamine starting material. The development of a divergent oxidative coupling for the formation of the benzofuro[2,3-b]indolenine and isochromano[3,4-b]indolenine moieties was key to this accomplishment.

    • David Lachkar
    • , Natacha Denizot
    • , Guillaume Bernadat
    • , Kadiria Ahamada
    • , Mehdi A. Beniddir
    • , Vincent Dumontet
    • , Jean-François Gallard
    • , Régis Guillot
    • , Karine Leblanc
    • , Elvis Otogo N'nang
    • , Victor Turpin
    • , Cyrille Kouklovsky
    • , Erwan Poupon
    • , Laurent Evanno
    •  & Guillaume Vincent
    Nature Chemistry 9, 793-798

News and Comment

  • News and Views |

    Natural products often serve as sources of new drugs, either directly or after synthetic modification, but site-selective functionalization of complex small molecules is challenging. Now, a method has been developed that enables selective modification of a wide range of natural products by engaging a benzyne intermediate in a variety of reaction modes.

    • Sarah Z. Tasker
    •  & Paul J. Hergenrother
    Nature Chemistry 9, 504-506
  • Comments and Opinion |

    Adam Nelson and Stuart Warriner, from the University of Leeds, talk with Nature Chemistry about their work to develop viable synthetic strategies for preparing new chemical structures in parallel with the identification of desirable biological activity.

    Nature Chemistry 6, 845-846
  • News and Views |

    Two approaches have emerged for creating libraries of compounds for use in biological screening assays for drug discovery — fragment-based ligand design and diversity-oriented synthesis. Advocates of each approach discuss their favoured strategy.

    • Philip J. Hajduk
    • , Warren R. J. D. Galloway
    •  & David R. Spring
    Nature 470, 42-43