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Synfacts 2013; 9(1): 0014
DOI: 10.1055/s-0032-1317718
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Akt Inhibitor GDC-0068

Contributor(s):
Philip Kocienski
Blake JF * et al. Array Biopharma Inc., Boulder and Genentech Inc., South San Francisco, USA
Discovery and Preclinical Pharmacology of a Selective ATP-Competitive Akt Inhibitor (GDC-0068) for the Treatment of Human Tumors.

J. Med. Chem. 2012;
55: 8110-8127
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Further Information

Publication History

Publication Date:
17 December 2012 (online)

 
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Key words

GDC-0068 - serine/threonine kinase - Akt inhibitor - Favorskii ring contraction - Noyori asymmetric transfer hydrogenation - pyrimidine N-oxide rearrangement

Significance

Akt is a kinase that controls cellular processes by phosphorylating substrates involved in apoptosis, transcription, cell cycle progression and translation. GDC-0068 is an Akt inhibitor that is in clinical trials for the treatment of cancer.


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Comment

Key steps in the synthesis depicted are (1) the use of a Favorskii ring contraction in the conversion of (R)-pulegone (A) to the ester B and (2) the Noyori asymmetric transfer hydrogenation of ketone J.


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