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Author Notes:
Correspondence: R.F. Schinazi; Email: rschina@emory.edu
Disclosures: Dr. R.F. Schinazi is the Founder of RFS Pharma, LLC, a major shareholder of RFS Pharma, LIC and an inventor of DAPD/APD and may receive royalties from the future sales of these drugs; Emory received no funding from RFS Pharma, LLC to perform this work and vice versa.
Subjects:
Research Funding:
Supported in part by NIH CFAR grant 2P30-AI-050409 and by the Department of Veterans Affairs.
Keywords:
- Amdoxovir
- DAPD
- Diaminopurine
- Dioxolane
- Nucleoside
- Glycosylation
Scaleable processes for the synthesis of (-)-β-D-2,6-diaminopurine dioxolane (Amdoxovir, DAPD) and (-)-β-D-2-aminopurine dioxolane (APD)
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Abstract:
An efficient and scalable synthesis of (−)-DAPD and (−)-APD has been developed. We discovered that t-butyl cyanoacetate can be used as a new additive for the sugar nucleoside base coupling step en route to DAPD with improved β-selectivity and an isolated yield four fold greater than the original process scale method. Using this new process, (−)-DAPD has been prepared on greater than 20 g scale. In the synthesis of (−)-APD, a key enzyme-catalyzed hydrolysis reaction afforded the water-soluble deprotected α-anomer while leaving the β-anomer completely untouched.
Copyright information:
© 2011 Elsevier Ltd. All rights reserved
This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).
