Divergent pathway for the solid-phase conversion of aromatic acetylenes to carboxylic acids, α-ketocarboxylic acids, and methyl ketones
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Divergent pathway for the solid-phase conversion of aromatic acetylenes to carboxylic acids, α-ketocarboxylic acids, and methyl ketones. / Le Quement, Sebastian T.; Nielsen, Thomas E.; Meldal, Morten.
I: Journal of Combinatorial Chemistry, Bind 10, Nr. 4, 07.2008, s. 546-556.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Divergent pathway for the solid-phase conversion of aromatic acetylenes to carboxylic acids, α-ketocarboxylic acids, and methyl ketones
AU - Le Quement, Sebastian T.
AU - Nielsen, Thomas E.
AU - Meldal, Morten
PY - 2008/7
Y1 - 2008/7
N2 - An efficient divergent pathway for the selective and quantitative solid-phase conversion of aromatic acetylenes to the corresponding carboxylic acids, α-keto-carboxylic acids, and methyl ketones is presented. A range of aromatic trimethylsilyl-protected acetylene building blocks was synthesized in excellent yields using a Sonogashira cross-coupling protocol and used in solid-phase synthesis on PEGA resin. Dependent on the selection of conditions, the same solid-supported alkyne could be quantitatively converted to an aromatic carboxylic acid, an aromatic α-ketocarboxylic acid, or an aromatic methyl ketone. The conversion to carboxylic acid involved an OsO4/NaIO 4/HMTA-mediated oxidative cleavage of the silyl-deprotected alkyne to provide the aromatic carboxylate in excellent yield. The α-ketocarboxylic acids were obtained by direct treatment of the trimethylsilyl-protected alkyne with OsO4/NMO/HMTA, while the ketones were obtained by simple acid-mediated hydration of the alkyne using aqueous TFA. In general, all products were obtained in excellent purities, typically above 90%. In addition, it was shown mat the alkyne-containing building blocks could easily be incorporated into resin-bound peptides and after chemoselective conversion of the alkyne the new functional groups could be used for further derivatization into peptidomimetic compounds.
AB - An efficient divergent pathway for the selective and quantitative solid-phase conversion of aromatic acetylenes to the corresponding carboxylic acids, α-keto-carboxylic acids, and methyl ketones is presented. A range of aromatic trimethylsilyl-protected acetylene building blocks was synthesized in excellent yields using a Sonogashira cross-coupling protocol and used in solid-phase synthesis on PEGA resin. Dependent on the selection of conditions, the same solid-supported alkyne could be quantitatively converted to an aromatic carboxylic acid, an aromatic α-ketocarboxylic acid, or an aromatic methyl ketone. The conversion to carboxylic acid involved an OsO4/NaIO 4/HMTA-mediated oxidative cleavage of the silyl-deprotected alkyne to provide the aromatic carboxylate in excellent yield. The α-ketocarboxylic acids were obtained by direct treatment of the trimethylsilyl-protected alkyne with OsO4/NMO/HMTA, while the ketones were obtained by simple acid-mediated hydration of the alkyne using aqueous TFA. In general, all products were obtained in excellent purities, typically above 90%. In addition, it was shown mat the alkyne-containing building blocks could easily be incorporated into resin-bound peptides and after chemoselective conversion of the alkyne the new functional groups could be used for further derivatization into peptidomimetic compounds.
UR - http://www.scopus.com/inward/record.url?scp=49049084845&partnerID=8YFLogxK
U2 - 10.1021/cc8000037
DO - 10.1021/cc8000037
M3 - Journal article
C2 - 18588350
AN - SCOPUS:49049084845
VL - 10
SP - 546
EP - 556
JO - ACS Combinatorial Science
JF - ACS Combinatorial Science
SN - 2156-8952
IS - 4
ER -
ID: 321826933