Synthesis and antiproliferative activity of 3α-hydroxyl-3β-methoxymethyl-5α-pregnan-20-one with a C-21 hydrophilic substituent

Abstract

A series of 3α-hydroxyl-3β-methoxymethyl-5α-pregnan-20-ones 7-15 possessing C-21 hydrophilic substituents were synthesized from the corresponding C21-bromo steroid 6 in 24%-89% yields. The hydrophilic groups include amino group from Delépine reaction, hydroxyl group from the hydrolysis by cesium formate in anhydrous MeOH, and amino acids, hydrazinecarboxamide, piperazine, and imidazolyl from nucleophilic substitution. Acylation and O-glycosylation of the resulting C-21 hydroxylsteroid also afforded the corresponding acylated and glycosylated products in excellent yield (77%-89%). Among the compounds, aminosteroid 7 and piperazinyl steroid 14 were most potent against the proliferation of human prostate cancer PC-3 cells with IC 50 values of 42 and 82 μmol L −1 , respectively.

Dual-Stimuli-Responsive Probes for Detection of Ovarian Cancer Cells and Quantification of Both pH and Enzyme Activity

“…13 C NMR (100 MHz, CDCl3, 25 °C): δ = 22.8, 23.7, 55.2, 71.8, 113.6, 123.3, 124.6, 125.5, 126.1, 128.7, 128.9, 137.2, 146.6, 147.0, 147.4, 151.6, 153.7, 159.2. HRMS (ESI) calcd for C20H21N2O3 ([M+H] + ): 337.1552, found: 337.1555.gal-BP-PMB: Under nitrogen atmosphere, a solution of BP-PMB (0.3 g, 0.89 mmol), 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide48 (0.4 g, 1.8 mmol), and Ag2O (0.7 g, 1.9 mmol) in MeCN (20 mL) was stirred at 60 °C for 12 h. The reaction mixture was cool down to room temperture and filtered through a Celite pad. The filtrate was concentrated under vacuum to remove MeCN.…”

Photoaffinity labeling identifies an intersubunit steroid-binding site in heteromeric GABA type A (GABAA) receptors

“…Derk Hogenkamp and Kelvin Gee for the gifts of UCI-50027 (41) and CCD-3693 (40) and Drs. Shuo en Tsai and Fung Fuh Wong for the resynthesis and gift of 3b-CH 3 OCH 2 -THDOC (42).…”