Synthesis of a Family of Spirocyclic Scaffolds; Building Blocks for the Exploration of Chemical Space
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Issue Date
2013-07-05Author
Kumar, Sarvesh
Thornton, Paul
Painter, Thomas O.
Jain, Prashi
Downard, Jared
Douglas, Justin T.
Santini, Conrad
Publisher
American Chemical Society
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Organic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jo400738b.
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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: Through stepwise changes in the size of the nitrogen bearing ring.
Through the oxidation state of the carbon centered point of diversification.
Through the relative stereochemical orientation of the two diversification sites in those members that are stereogenic.
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 sp3 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.
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Citation
Kumar, S., Thornton, P., Painter, T. O., Jain, P., Downard, J., Douglas, J. T., & Santini, C. (2013). Synthesis of a Family of Spirocyclic Scaffolds; Building Blocks for the Exploration of Chemical Space. The Journal of Organic Chemistry, 78(13), 6529–6539. http://doi.org/10.1021/jo400738b
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