Details

Autor(en) / Beteiligte

• Fandrick, Keith R
• Mulder, Jason A
• Patel, Nitinchandra D
• Gao, Joe
• Konrad, Michael
• Archer, Elizabeth
• Buono, Frederic G
• Duran, Adil
• Schmid, Rolf
• Daeubler, Juergen
• Desrosiers, Jean-Nicolas
• Zeng, Xingzhong
• Rodriguez, Sonia
• Ma, Shengli
• Qu, Bo
• Li, Zhibin
• Fandrick, Daniel R
• Grinberg, Nelu
• Lee, Heewon
• Bosanac, Todd
• Takahashi, Hidenori
• Chen, Zhidong
• Bartolozzi, Alessandra
• Nemoto, Peter
• Busacca, Carl A
• Song, Jinhua J
• Yee, Nathan K
• Mahaney, Paige E
• Senanayake, Chris H

Titel

Development of an Asymmetric Synthesis of a Chiral Quaternary FLAP Inhibitor

Ist Teil von

• Journal of organic chemistry, 2015-02, Vol.80 (3), p.1651-1660

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• A practical sequence involving a noncryogenic stereospecific boronate rearrangement followed by a robust formylation with an in situ generated DCM anion has been developed for the asymmetric construction of an all-carbon quaternary stereogenic center of a FLAP inhibitor. The key boronate rearrangement was rendered noncryogenic and robust by using LDA as the base and instituting an in situ trapping of the unstable lithiated benzylic carbamate with the boronic ester. A similar strategy was implemented for the DCM formylation reaction. It was found that the 1,2-boronate rearrangement for the formylation reaction could be temperature-controlled, thus preventing overaddition of the DCM anion and rendering the process reproducible. The robust stereospecific boronate rearrangement and formylation were utilized for the practical asymmetric synthesis of a chiral quaternary FLAP inhibitor.