Adamczyk M, Mattingly P G, Reddy R E
Division Organic Chemistry Research, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Steroids. 1997 Jun;62(6):462-7. doi: 10.1016/s0039-128x(97)00015-9.
6-Oxoestradiol (2) was protected as its bis[(2-trimethylsilylethoxy)methyl] ether (4) and converted to the corresponding oxime (4). The oxime (4) on reduction with zinc in ethanol afforded the bis-SEM ether of 6-alpha-aminoestradiol (5) in 96% epimeric excess. Subsequently, 5 was hydrolyzed with HF to 6-alpha-aminoestradiol (6) in good yield. The absolute stereochemistry of the amino group in 6 was established by NMR and confirmed by X-ray crystallography on the corresponding 4-bromobenzamide derivative (9). Treatment of amine (6) with 6-(t-butoxycarbonylamino)hexanoic acid succinimidyl ester (10) followed by hydrolysis produced the amine (12) with a C-6 linker. The fluorescent probes (7 and 13) were prepared from 6 and 12 respectively, in 54-60% yield and > 99% purity.
6-氧代雌二醇（2）被保护为其二[(2-三甲基硅基乙氧基)甲基]醚（4），并转化为相应的肟（4）。肟（4）在乙醇中用锌还原，以96%的差向异构体过量得到6-α-氨基雌二醇（5）的双-SEM醚。随后，5用HF水解，以良好的产率得到6-α-氨基雌二醇（6）。6中氨基的绝对立体化学通过NMR确定，并通过相应的4-溴苯甲酰胺衍生物（9）的X射线晶体学得到证实。用6-(叔丁氧羰基氨基)己酸琥珀酰亚胺酯（10）处理胺（6），然后水解，得到带有C-6连接基的胺（12）。荧光探针（7和13）分别由6和12制备，产率为54-60%，纯度>99%。
