Carrillo-Marquez Tomas, Caggiano Lorenzo, Jackson Richard F W, Grabowska Urszula, Rae Alastair, Tozer Matthew J
Department of Chemistry, Dainton Building, University of Sheffield, Brook Hill, Sheffield, UKS3 7HF.
Org Biomol Chem. 2005 Nov 21;3(22):4117-23. doi: 10.1039/b512784j. Epub 2005 Oct 3.
Two distinct routes to beta-cycloalkylalanine derivatives have been developed. The first route employs the reaction of the iodoalanine-derived zinc-copper reagent 2 with cycloalk-1-en-3-yl phosphates, and the second uses the palladium-catalysed coupling of the iodoalanine-derived zinc reagent 1 with cycloalkenyl triflates; in each case, catalytic hydrogenation of the unsaturated product leads to the protected beta-cycloalkylalanine. The latter route allows access to a range of cycloalkyl derivatives, with ring sizes of 5-8. beta-(1-Methyl-1-cyclohexyl)alanine may be prepared using reaction of the zinc-copper reagent 2 with 3-methyl-2-cyclohexenyl chloride, followed by hydrogenation. The corresponding cyclopentyl derivative may be prepared by reaction of the same zinc-copper reagent 2 with diethyl geranylphosphate, followed by ring-closing metathesis and hydrogenation.
已开发出两种合成β-环烷基丙氨酸衍生物的不同路线。第一条路线采用碘代丙氨酸衍生的锌铜试剂2与环烷-1-烯-3-基磷酸酯反应，第二条路线则是碘代丙氨酸衍生的锌试剂1与环烯基三氟甲磺酸酯的钯催化偶联反应；在每种情况下，不饱和产物的催化氢化反应都会生成受保护的β-环烷基丙氨酸。后一条路线能够合成一系列环大小为5至8的环烷基衍生物。β-(1-甲基-1-环己基)丙氨酸可通过锌铜试剂2与3-甲基-2-环己烯基氯反应，随后进行氢化反应来制备。相应的环戊基衍生物可通过相同的锌铜试剂2与香叶基磷酸二乙酯反应，随后进行闭环复分解反应和氢化反应来制备。
