Sariaslani F S, Eckenrode F M, Beale J M, Rosazza J P
J Med Chem. 1984 Jun;27(6):749-54. doi: 10.1021/jm00372a008.
16-O- Acetylvindoline (1a) was oxidatively transformed into an iminium derivative (2a) by copper oxidases (laccase and human ceruloplasmin), an unknown enzyme system(s) of Streptomyces griseus, and the chemical oxidizing agent 2,3-dichloro-5,6- dicyano -1,4-benzoquinone ( DDQ ). The iminium derivative (2a) was isolated from enzymatic and chemical oxidation mixtures and was identified by spectral and chemical techniques. Reduction of the iminium compound with sodium borodeuteride provided monodeuterated 16-O- acetylvindoline (1b) as the sole product. Mass spectral analysis indicated that the deuterium atom was introduced into position C-3 of the piperidine portion of the alkaloid structure. The location and stereochemistry of the deuterium atom were confirmed by high-field 1H and 2H NMR analyses of the deuterated product to be in the 2H alpha orientation. Hydrolysis of the 16-O-acetyl functional group from the iminium derivative (2a) resulted in the production of a previously identified dimer (5), which forms by intramolecular etherification through the reactive enamine (3). The iminium derivative (2a) reacts with cyanide to provide complex mixtures of products, one of which was identified by mass spectrometry as a cyanide addition product. The results confirm the existence of a reactive iminium intermediate formed by all of the biochemical and chemical systems examined.
16 - O - 乙酰文朵灵（1a）通过铜氧化酶（漆酶和人血浆铜蓝蛋白）、灰色链霉菌的一种未知酶系统以及化学氧化剂2,3 - 二氯 - 5,6 - 二氰基 - 1,4 - 苯醌（DDQ）被氧化转化为亚胺鎓衍生物（2a）。亚胺鎓衍生物（2a）从酶促氧化和化学氧化混合物中分离出来，并通过光谱和化学技术进行鉴定。用硼氘化钠还原亚胺鎓化合物得到单氘代的16 - O - 乙酰文朵灵（1b）作为唯一产物。质谱分析表明，氘原子被引入到生物碱结构哌啶部分的C - 3位。通过对氘代产物的高场1H和2H NMR分析证实了氘原子的位置和立体化学为2Hα取向。从亚胺鎓衍生物（2a）上水解16 - O - 乙酰官能团导致产生一种先前鉴定的二聚体（5），其通过反应性烯胺（3）进行分子内醚化形成。亚胺鎓衍生物（2a）与氰化物反应生成复杂的产物混合物，其中之一通过质谱鉴定为氰化物加成产物。结果证实了在所研究的所有生化和化学系统中形成的反应性亚胺鎓中间体的存在。
