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 language | English (US) |
|---|---|
| Pages (from-to) | 6595-6609 |
| Number of pages | 15 |
| Journal | Tetrahedron |
| Volume | 53 |
| Issue number | 19 |
| DOIs | |
| State | Published - May 12 1997 |
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ASJC Scopus subject areas
- Biochemistry
- Organic Chemistry
- Drug Discovery
Cite this
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 journal › Article
}
TY - JOUR
T1 - The solid-phase combinatorial synthesis of β-thioketones
AU - Chen, Chixu
AU - Ahlberg Randall, Lisa A.
AU - Miller, R. Bryan
AU - Jones, A. Daniel
AU - Kurth, Mark J.
PY - 1997/5/12
Y1 - 1997/5/12
N2 - 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.
AB - 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.
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U2 - 10.1016/S0040-4020(97)00219-6
DO - 10.1016/S0040-4020(97)00219-6
M3 - Article
AN - SCOPUS:0030896376
VL - 53
SP - 6595
EP - 6609
JO - Tetrahedron
JF - Tetrahedron
SN - 0040-4020
IS - 19
ER -