An efficient stereoselective synthesis of 6-alpha-aminoestradiol: preparation of estradiol fluorescent probes.
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.
Adamczyk
M
M
Division Organic Chemistry Research, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Mattingly
P G
PG
Reddy
R E
RE
D018360:Crystallography, X-Ray; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D005456:Fluorescent Dyes / Q000138:chemical synthesis*; D008956:Models, Chemical; D008958:Models, Molecular; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D005456:Fluorescent Dyes; C107425:6-aminoestradiol; D004958:Estradiol; C012396:6-ketoestradiol