Zanotti G, Möhringer C, Wieland T
C.N.R. Institute of Pharmaceutical Chemistry, University La Sapienza, Rome, Italy.
Int J Pept Protein Res. 1987 Oct;30(4):450-9. doi: 10.1111/j.1399-3011.1987.tb03353.x.
Analogs of amaninamide, due to the absence of a 6-hydroxy group in the tryptophan moiety, are more easily accessible by synthesis than derivatives of alpha-amanitin. Syntheses of bicyclic octapeptide thioethers 1f-1m have been carried out starting from linear Hpi-S-trityl-octapeptides (3), cyclization by intramolecular 2'-indolylthioether formation yielding monocyclic peptides (2) and final cyclization by DCCI. One of the bicyclic thioethers was oxidized to yield the corresponding chromatographically separated (R)- and (S)-sulfoxides, respectively. The products were characterized by RF-values, u.v. and CD spectra as well as by mass (FAB) spectroscopy. The widely differing inhibitory activities on RNA polymerase II (or B) from calf thymus are listed.
由于色氨酸部分不存在6-羟基，氨甲环酸类似物比α-鹅膏蕈碱衍生物更容易通过合成获得。双环八肽硫醚1f-1m的合成是从线性Hpi-S-三苯甲基八肽（3）开始的，通过分子内2'-吲哚硫醚形成进行环化生成单环肽（2），最后通过二环己基碳二亚胺进行环化。其中一种双环硫醚被氧化，分别得到相应的经色谱分离的（R）-和（S）-亚砜。产物通过比移值、紫外光谱和圆二色光谱以及质谱（快原子轰击）进行表征。列出了它们对小牛胸腺RNA聚合酶II（或B）的广泛不同的抑制活性。
