M. Adamczyk et al., AN EFFICIENT STEREOSELECTIVE SYNTHESIS OF 6-ALPHA-AMINOESTRADIOL - PREPARATION OF ESTRADIOL FLUORESCENT-PROBES, Steroids, 62(6), 1997, pp. 462-467
6-Oxoestradiol (2) was protected as its bis[(2-trimethylsilylethoxy)me
thyl] ether (4) and converted to the corresponding oxime (4). The oxim
e (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 a
bsolute stereochemistry of the amino group in 6 was established by NMR
and confirmed by X-ray crystallography on the corresponding 4-bromobe
nzamide derivative (9). Treatment of amine (6) with 6(t-butoxycarbonyl
amino)hexanoic acid succinimidyl ester (10) followed by hydrolysis pro
duced 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. (C) 1997 Elsevier Science Inc.