title: Synthesis of a family of spirocyclic scaffolds: building blocks for the exploration of chemical space.
abstract: This report describes the preparation of a series of 17 novel racemic spirocyclic scaffolds that are intended for the creation of compound libraries by parallel synthesis for biological screening. Each scaffold features two points of orthogonal diversification. The scaffolds are related to each other in four ways: (1) through stepwise changes in the size of the nitrogen-bearing ring; (2) through the oxidation state of the carbon-centered point of diversification; (3) through the relative stereochemical orientation of the two diversification sites in those members that are stereogenic; and (4) through the provision of both saturated and unsaturated versions of the furan ring in the scaffold series derived from 3-piperidone. The scaffolds provide incremental changes in the relative orientation of the diversity components that would be introduced onto them. The scaffolds feature high sp(3) carbon content which is essential for the three-dimensional exploration of chemical space. This characteristic is particularly evident in those members of this family that bear two stereocenters, i.e., the two series derived from 3-piperidone and 3-pyrrolidinone. In the series derived from 3-piperidone we were able to "split the difference" between the two diastereomers by preparation of their corresponding unsaturated version.
authors.affiliation: Center for Chemical Methodologies and Library Development, The University of Kansas, 2034 Becker Drive, Lawrence, Kansas 66047, USA.
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thornton
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Painter
authors.forename: Prashi
authors.initials: P
authors.lastname: Jain
authors.forename: Jared
authors.initials: J
authors.lastname: Downard
authors.forename: Justin T
authors.initials: JT
authors.lastname: Douglas
authors.forename: Conrad
authors.initials: C
authors.lastname: Santini
mesh_terms: D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D006571:Heterocyclic Compounds; D013141:Spiro Compounds