Cyclopentitol as a scaffold for a natural product-like compound library for drug discovery

Jalindar D Padwal; Dmitri V Filippov; Bharat D Narhe; Sjoerd Aertssen; Remmelt Jan Beuving; Jorg C J Benningshof; Gijsbert A van der Marel; Herman S Overkleeft; Mario van der Stelt

doi:10.1016/j.bmc.2015.01.040

Cyclopentitol as a scaffold for a natural product-like compound library for drug discovery

Bioorg Med Chem. 2015 Jun 1;23(11):2650-5. doi: 10.1016/j.bmc.2015.01.040. Epub 2015 Jan 31.

Authors

Jalindar D Padwal¹, Dmitri V Filippov¹, Bharat D Narhe¹, Sjoerd Aertssen², Remmelt Jan Beuving², Jorg C J Benningshof², Gijsbert A van der Marel¹, Herman S Overkleeft¹, Mario van der Stelt³

Affiliations

¹ Leiden Institute of Chemistry, Gorlaeus Laboratories, PO Box 9502, Universiteit Leiden, 2300 RA Leiden, The Netherlands.
² Mercachem, Kerkenbos 1013, 6546 BB Nijmegen, The Netherlands.
³ Leiden Institute of Chemistry, Gorlaeus Laboratories, PO Box 9502, Universiteit Leiden, 2300 RA Leiden, The Netherlands. Electronic address: m.van.der.stelt@chem.leidenuniv.nl.

PMID: 25691210
DOI: 10.1016/j.bmc.2015.01.040

Abstract

A concise and efficient synthesis of cyclopentitols as a scaffold for a two-dimensional compound library for drug discovery is described. Starting from d-mannose, the key steps are Wittig olefination and ring-closing metathesis (RCM) followed by a [3,3]-sigmatropic Overmann rearrangement to form an sp(3)-rich, natural product-like scaffold from which a focused compound library with different functionalities is prepared.

Keywords: Cyclopentitols; Drug discovery; Focused library; Natural product-like compounds.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Products / chemical synthesis*
Cycloaddition Reaction*
Drug Discovery*
Mannose / chemistry*
Molecular Structure
Pentoses / chemistry*
Polycyclic Compounds / chemistry*
Small Molecule Libraries / chemical synthesis*

Substances

Biological Products
Pentoses
Polycyclic Compounds
Small Molecule Libraries
Mannose