Synthesis of 6 beta-aminoestradiol and its biotin, acridinium, and fluorescein conjugates.
Amination of 3,17 beta-Bis[(2-trimethylsilylethoxy) methoxy]-1,3,5(10)-estratriene-6-one (2) using NaCNBH4 and NH4OAc afforded 3,17-bis(SEM)-6-aminoestradiol (3) as a mixture of alpha and beta-isomers in 60:40 ratio. Hydrolysis of the mixture of 3 using HF and separation by preparative high-performance liquid chromatography afforded pure 6 beta-aminoestradiol (4) in good yield. The relative stereochemistry of the amino group in 4 was established by NMR. The biotinylated estradiol probe (7), chemiluminescent probe (9), and fluorescent probe (11), were prepared from 6 beta-aminoestradiol (4) and the corresponding biotin, 10-(3-sulfopropyl)-N-tosyl-N-(3-carboxypropyl)acridinium-9-carboxamide, and 5-carboxyfluorescein N-succinimidyl esters in 43-63% yields and > 99% purity.
Adamczyk
M
M
Division Organic Chemistry Research, Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.
Mattingly
P G
PG
Reddy
R E
RE
D000166:Acridines / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D019793:Fluorescein / Q000737:chemistry*; D005456:Fluorescent Dyes; D009682:Magnetic Resonance Spectroscopy
D000166:Acridines; D005456:Fluorescent Dyes; C107425:6-aminoestradiol; D004958:Estradiol; D001710:Biotin; D019793:Fluorescein