Rew Yosup, Goodman Murray
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093-0343, USA.
J Org Chem. 2002 Dec 13;67(25):8820-6. doi: 10.1021/jo020447l.
An efficient solid-phase synthetic route is described for the preparation of 13-membered amine-bridged cyclic enkephalin analogues (ABEs) 1a and 1c-1j (Figure 1) resulting from a sulfonamide-containing peptide whose backbone is bound to a resin. The Fukuyama-Mitsunobu reaction of the 2-nitrobenzenesulfonyl-protected amine bound to the solid support with protected aminoethanol in the presence of triphenylphosphine and diisopropyl azodicarboxylate (DIAD) is utilized to prepare a resin-bound sulfonamide-protected secondary amine. After peptide cyclization, this protected amine functionality becomes the "amine bridge" of the target molecule. In addition, the reagent DIAD was found to be a superior reagent compared to diethyl azodicarboxylate (DEAD) in the solid-phase Fukuyama-Mitsunobu reaction.
描述了一种高效的固相合成路线，用于制备13元胺桥连环脑啡肽类似物（ABEs）1a和1c - 1j（图1），其由含磺酰胺的肽制备，该肽的主链与树脂相连。在三苯基膦和偶氮二羧酸二异丙酯（DIAD）存在下，将与固相载体相连的2-硝基苯磺酰基保护的胺与保护的氨基乙醇进行福山-光延反应，以制备与树脂相连的磺酰胺保护的仲胺。肽环化后，这种受保护的胺官能团成为目标分子的“胺桥”。此外，发现在固相福山-光延反应中，试剂DIAD比偶氮二羧酸二乙酯（DEAD）更优越。
