title: Construction of a 3D-shaped, natural product like fragment library by fragmentation and diversification of natural products.
abstract: A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD).
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Basel, Switzerland.
authors.forename: Horst
authors.initials: H
authors.lastname: Prescher
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Basel, Switzerland.
authors.forename: Guido
authors.initials: G
authors.lastname: Koch
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Basel, Switzerland.
authors.forename: Tim
authors.initials: T
authors.lastname: Schuhmann
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Ertl
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Basel, Switzerland.
authors.forename: Alex
authors.initials: A
authors.lastname: Bussenault
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Cambridge, MA, USA.
authors.forename: Meir
authors.initials: M
authors.lastname: Glick
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Basel, Switzerland.
authors.forename: Ina
authors.initials: I
authors.lastname: Dix
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Basel, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Petersen
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Basel, Switzerland. Electronic address: dimitrios.lizos@novartis.com.
authors.forename: Dimitrios E
authors.initials: DE
authors.lastname: Lizos
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003572:Cytochalasins / Q000138:chemical synthesis / Q000737:chemistry*; D055808:Drug Discovery; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D001688:Biological Products; D003572:Cytochalasins; D007783:Lactones; D054852:Small Molecule Libraries; D013141:Spiro Compounds; C000621556:massarigenin C; C007215:cytochalasin E
keywords: Fragment based drug discovery; Fragment library; Natural product likeness; Natural products; Rearrangement