Efficient synthesis of protected cyclopropyl beta-aspartylphosphates.
The in situ reaction of protected dehydroamino acids with derivatives of vinyldiazomethane leads to good to excellent yields of vinyl cyclopropanes via 3 + 2 dipolar cycloaddition followed by N(2) extrusion. Chromatographic separation of the cyclopropane diastereomeric products, followed by characterisation by (1)H NMR and X-ray crystallography allowed the cis and trans diastereomers to be easily identified. Oxidative cleavage of the vinyl moiety then led directly to protected cyclopropane aspartic acid derivatives in three steps from commercially available materials. These compounds were converted to protected methylenephosphonate, difluoromethylenephosphonate and phosphoramidate analogues of [small beta]-aspartyl phosphate.
Adams
Luke A
LA
School of Chemistry, University of Bristol, Cantock's Close, Bristol, UK.
Charmant
Jonathan P H
JP
Cox
Russell J
RJ
Walter
Magnus
M
Whittingham
William G
WG
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D002384:Catalysis; D003521:Cyclopropanes / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure
D003521:Cyclopropanes; C032197:beta-aspartyl phosphate; D001224:Aspartic Acid; C030797:cyclopropane