The solid-phase combinatorial synthesis of β-thioketones

Chixu Chen, Lisa A. Ahlberg Randall, R. Bryan Miller, A. Daniel Jones, Mark J. Kurth

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A solid-phase split-mix organic synthesis method was developed which, by two synthetic steps, converts polymer-bound aldehyde I into resins III. Step one consists of dividing I into three equal portions in separate flasks, condensing each with a different ylide, and subsequently recombining to give II. This mixture of beads was again equally divided into three flasks, and each flask treated with a thiolate Michael donor. Prior to recombining the contents of each flask (i.e., sub-library), samples of each resin were removed and incubated with a THF/HCO2H mixture to liberate the small molecule products. GC-MS established that each sub-library (A, B, and C) contained the three anticipated formate esters. In addition, GC analysis illustrates that, while there were no purification steps involved in this solid-phase analogous organic synthesis save bead washings between steps, the desired products are obtained in excellent purity. Single bead (200-400 mesh) selection from library D (combined sub-libraries A-C), solvolysis, and GC-MS analysis shows that compound identities can be established on a per bead basis.

Original languageEnglish (US)
Pages (from-to)6595-6609
Number of pages15
JournalTetrahedron
Volume53
Issue number19
DOIs
StatePublished - May 12 1997

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Solid-Phase Synthesis Techniques
Libraries
Synthetic Chemistry Techniques
Formic Acid Esters
Resins
Aldehydes
Washing
Purification
Polymers
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Chen, C., Ahlberg Randall, L. A., Miller, R. B., Jones, A. D., & Kurth, M. J. (1997). The solid-phase combinatorial synthesis of β-thioketones. Tetrahedron, 53(19), 6595-6609. https://doi.org/10.1016/S0040-4020(97)00219-6

The solid-phase combinatorial synthesis of β-thioketones. / Chen, Chixu; Ahlberg Randall, Lisa A.; Miller, R. Bryan; Jones, A. Daniel; Kurth, Mark J.

In: Tetrahedron, Vol. 53, No. 19, 12.05.1997, p. 6595-6609.

Research output: Contribution to journalArticle

Chen, C, Ahlberg Randall, LA, Miller, RB, Jones, AD & Kurth, MJ 1997, 'The solid-phase combinatorial synthesis of β-thioketones', Tetrahedron, vol. 53, no. 19, pp. 6595-6609. https://doi.org/10.1016/S0040-4020(97)00219-6
Chen C, Ahlberg Randall LA, Miller RB, Jones AD, Kurth MJ. The solid-phase combinatorial synthesis of β-thioketones. Tetrahedron. 1997 May 12;53(19):6595-6609. https://doi.org/10.1016/S0040-4020(97)00219-6
Chen, Chixu ; Ahlberg Randall, Lisa A. ; Miller, R. Bryan ; Jones, A. Daniel ; Kurth, Mark J. / The solid-phase combinatorial synthesis of β-thioketones. In: Tetrahedron. 1997 ; Vol. 53, No. 19. pp. 6595-6609.
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