Synthesis of spirohydantoins and spiro-2,5-diketopiperazines via resin-bound cyclic alpha,alpha-disubstituted alpha-amino esters
| Autor: | Chris G. Kruse, Bart J. van Steen, Leo A. J. M. Sliedregt, Arnold van Loevezijn, Leon W. A. van Berkom, Floris P. J. T. Rutjes, Hans W. Scheeren, Mohamed Kalmoua, George J. T. Kuster |
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| Rok vydání: | 2005 |
| Předmět: |
Magnetic Resonance Spectroscopy
Stereochemistry Imine Synthetic Organic Chemistry Mass Spectrometry Piperazines chemistry.chemical_compound Combinatorial Chemistry Techniques Spiro Compounds Amino Acids chemistry.chemical_classification Amino esters Molecular Structure Alkene Hydantoins Esters General Chemistry Isocyanate Cycloaddition PyBOP Resins Synthetic chemistry Cyclization Nitro Knoevenagel condensation Chromatography Liquid |
| Zdroj: | Journal of Combinatorial Chemistry, 8, 85-94 Journal of Combinatorial Chemistry, 8, 1, pp. 85-94 |
| ISSN: | 1520-4766 |
| Popis: | A seven-step solid-phase synthesis of spirohydantoins and an eight-step solid-phase synthesis of spiro-2,5-diketopiperazines is reported. Key intermediate in the synthesis of both compound libraries is the resin-bound cyclic alpha,alpha-disubstituted alpha-amino ester, which can be obtained after selective homogeneous reduction of the aliphatic nitro ester using tin(II) chloride dihydrate. Nitro ester, in turn, is synthesized by a high-pressure-assisted [4 + 2] cycloaddition of resin-bound nitro alkene and butadiene, whereas nitro alkene is obtained by a Knoevenagel condensation of resin-bound nitro acetate with an imine. Novel spirohydantoins are obtained by isocyanate coupling with the resin-bound amino ester 5, followed by cyclization cleavage using a base. Novel spiro-2,5-diketopiperazines are obtained by PyBOP coupling of a Fmoc-protected amino acid with resin-bound amino ester, followed by Fmoc deprotection and an acid-assisted cyclization cleavage. After preparation of seven different resin-bound alpha,alpha-disubstituted alpha-amino esters, a 7 x 8 compound library of spirohydantoins was synthesized using eight different isocyanates, and a 7 x 8 compound library of spiro-2,5-diketopiperazines was synthesized using eight different Fmoc amino acids. |
| Databáze: | OpenAIRE |
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