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. 2013 Jul 8;15(7):344-9.
doi: 10.1021/co4000387. Epub 2013 Jun 26.

Construction of a spirooxindole amide library through nitrile hydrozirconation-acylation-cyclization cascade

Matthew G LaPorte  1 , Sammi Tsegay, Ki Bum Hong, Chunliang Lu, Cheng Fang, Lirong Wang, Xiang-Qun Xie, Paul E Floreancig
Affiliations

Construction of a spirooxindole amide library through nitrile hydrozirconation-acylation-cyclization cascade

Matthew G LaPorte et al. ACS Comb Sci. .

Abstract

A library of spirooxindoles containing varied elements of structural and stereochemical diversity has been constructed via a three step, one pot nitrile hydrozirconation-acylation-cyclization reaction sequence from common acyclic indole intermediates. The resulting library was evaluated for novelty through comparison with MLSMR and Maybridge compound collections.

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Figures

Figure 1
Figure 1
Oxindole marketed drugs and spirooxindole natural products.
Figure 2
Figure 2
Representative spirooxindole libraries.
Figure 3
Figure 3
X-ray structure of 15{5}.
Figure 4
Figure 4
MW and cLogP distribution of spirooxindole library.
Figure 5
Figure 5
Tanimoto coefficient (Tc) comparisons of spirooxindoles vs MLSMR collection.
Figure 6
Figure 6
3D Chemistry space matrix analyses of spirooxindoles vs Maybridge HitFinder™ library.
Figure 6
Figure 6
3D Chemistry space matrix analyses of spirooxindoles vs Maybridge HitFinder™ library.
Scheme 1
Scheme 1
Preparation of indoles 3{1-2}.
Scheme 2
Scheme 2
Nitrile hydrozirconation-acylation-cyclization cascade.
Scheme 3
Scheme 3
Preparation of an ester containing library. a Isolated yields; b Purities determined by LCMS/ELS; c Calculated properties from Schrödinger Maestro 8.5.207-QikProp, 2.1.
Scheme 4
Scheme 4
Preparation of syn-amido ester analogs. a Isolated yields; b Purities determined by LCMS/ELS; c Calculated properties from Schrödinger Maestro 8.5.207-QikProp, 2.1.
Scheme 5
Scheme 5
Preparation of additional spirooxindole library. a Isolated yields; b Purities determined by LCMS/ELS; c Calculated properties from Schrödinger Maestro 8.5.207-QikProp, 2.1.
Scheme 6
Scheme 6
Spirooxindole derivatizations. a Isolated yields; b Purities determined by LCMS/ELS; c Calculated properties from Schrödinger Maestro 8.5.207-QikProp, 2.1.
Scheme 7
Scheme 7
Unsubstituted spirooxindoles. a Isolated yields; b Purities determined by LCMS/ELS; c Calculated properties from Schrödinger Maestro 8.5.207-QikProp, 2.1.
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