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Published November 12, 2015 in Henry Rzepa's Blog

Derek Lowe has a recent post entitled " Another Funny-Looking Structure Comes Through ". He cites a recent medchem article[cite]10.1021/acsmedchemlett.5b00398[/cite] in which the following acetal sub-structure appears in a promising drug candidate (blue component below). His point is that orally taken drugs have to survive acid (green below) encountered in the stomach, and acetals are famously sensitive to hydrolysis (red below). But if

References

Organic ChemistryDrug DiscoveryBiochemistry

Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK_a Polar Moiety

https://doi.org/10.1021/acsmedchemlett.5b00398

Published November 3, 2015 in ACS Medicinal Chemistry Letters

Authors Chudi O. Ndubaku, James J. Crawford, Joy Drobnick, Ignacio Aliagas, David Campbell, Ping Dong, Laura M. Dornan, Sergio Duron, Jennifer Epler, Lewis Gazzard, Christopher E. Heise, Klaus P. Hoeflich, Diana Jakubiak, Hank La, Wendy Lee, Baiwei Lin, Joseph P. Lyssikatos, Jasna Maksimoska, Ronen Marmorstein, Lesley J. Murray, Thomas O’Brien, Angela Oh, Sreemathy Ramaswamy, Weiru Wang, Xianrui Zhao, Yu Zhong, Elizabeth Blackwood, Joachim Rudolph

Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives

https://doi.org/10.1039/p29890001265

Published January 1, 1989 in J. Chem. Soc., Perkin Trans. 2

Authors Patrick Camilleri, David Munro, Karen Weaver, David J. Williams, Henry S. Rzepa, Alexandra M. Z. Slawin

Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives

https://doi.org/10.1039/p29890001929

Published January 1, 1989 in J. Chem. Soc., Perkin Trans. 2

Authors Patrick Camilleri, David Munro, Karen Weaver, David J. Williams, Henry S. Rzepa, Alexandra M. Z. Slawin

Condensed Matter PhysicsGeneral Materials ScienceGeneral Chemistry

N,N,N′,N′-Tetramethylstreptamine 2,4,6-orthoformate hydrochloride

https://doi.org/10.1107/s1600536803006287

Published March 31, 2003 in Acta Crystallographica Section E Structure Reports Online

Authors Claus Beckmann, Peter G. Jones, Anthony J. Kirby

InChI=1S/C4H11NO2.C2H3O2.Cl.H2O/c1-7-3-4(5)2-6;1-2(3)4;;/h4,6H,1-3H2,5H3;1H3;;1H2/t4-;;;/m0.../s1PEWGYHILMGIKGN-WJXVXWFNSA-N

C 6 H 16 Cl 1 N 1 O 5

https://doi.org/10.14469/ch/191590

Published November 12, 2015

Authors Henry S Rzepa, Imperial College London, Imperial College London, Henry S Rzepa

# freq wb97xd/6-311g(d,p) scrf=(cpcm,solvent=water) geom=connectivity

Crystal StructureExperimental 3D CoordinatesCrystal SystemSpace GroupCell Parameters

CCDC 209989: Experimental Crystal Structure Determination

https://doi.org/10.5517/cc71hvl

Published January 1, 2003

Authors C. Beckmann, P.G. Jones, A.J. Kirby

Related Article: C.Beckmann, P.G.Jones, A.J.Kirby|2003|Acta Crystallogr.,Sect.E:Struct.Rep.Online|59|o566|doi:10.1107/S1600536803006287

How to stop (some) acetals hydrolysing.

References

Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pKa Polar Moiety

Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives

Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives

N,N,N′,N′-Tetramethylstreptamine 2,4,6-orthoformate hydrochloride

C 6 H 16 Cl 1 N 1 O 5

CCDC 209989: Experimental Crystal Structure Determination

Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK_a Polar Moiety