N-butyl, N-methyl, 11-[3′,17′ β-(dihydroxy)-1′,3′,5′(10′)- estratrien-16′ α-yl]-9(R/S)-bromo undecanamide: synthesis and 17β-HSD inhibiting, estrogenic and antiestrogenic activities

Pelletier, Joëlle D.; Labrie, Fernand; Poirier, Donald

doi:10.1016/0039-128x(94)90072-8

Cited by 32 publications

(14 citation statements)

References 25 publications

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“…tert-Butyldimethylsilyl)-estrone (21) 7. TBS-Cl (251 mg, 1.664 mmol) was added to a stirring solution of estrone (54) (300 mg, 1.110 mmol) and DMAP (10 mg, 0.08185 mmol) in pyridine (6 ml).The mixture was stirred until complete by TLC at which time the pyridine was removed rotary evaporation.…”

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confidence: 99%

Cerium(III) Chloride-Mediated Reactions of Sulfonamide Dianions

Johnson

Widlanski

2003

J. Org. Chem.

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Presented here is the first report on the ability of cerium(III) chloride to mediate high-yielding and, oftentimes, highly diastereoselective additions of N-benzyl-alpha, N-dilithio methanesulfonamide to aldehydes and ketones of biological importance. Smooth addition was effected to base-sensitive substrates such as Fmoc-protected alaninal, citral, 5-cholesten-3-one, uridine 5'-aldehyde, 3'-ketouridine, and 3'-ketothymidine. The reaction was chemoselective for aldehydes in the presence of nitriles. Acetoxy groups are labile and thus not suitable protecting groups for alcohols under these conditions. N-Benzyl-alpha, N-dilithio methanesulfonamide was found to be of sufficient basicity to cause enolate formation with sensitive substrates, such as 1-phenylacetone. However, the addition of cerium(III) chloride mediated the basicity of the dianion and suppressed enolate formation in these cases. Further, cerium(III) has general utility for the addition of various N-aliphatic/aromatic methanesulfonamide dianions to 3'-ketouridine.

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confidence: 99%

Cerium(III) Chloride-Mediated Reactions of Sulfonamide Dianions

Johnson

Widlanski

2003

J. Org. Chem.

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“…When less sterically hindered diborane (BH 3 ) (Hosoda et al, 1975;Pelletier, 1994;Sam et al, 1994) followed by alkaline hydrogen peroxide were employed as oxidative-hydroboration agents, the main reaction product was the 15,21-dihydroxylated derivative of 8. However, by changing the hydroborating agent to the more sterically bulky 9-BBN, highly regioselective hydroxylation at the C-21 position in 8 was attained without simultaneous formation of either 15-hydroxylated or 15,21-dihydroxylated analogs of 8.…”

Section: Resultsmentioning

confidence: 99%

Chemical synthesis of the 17-propanamide derivatives of stereoisomeric Δ14-17α- and 17β-estradiols: potential 17β-hydroxysteroid dehydrogenase inhibitors

Iida

Ogawa

Tamegai

et al. 2011

Chemistry and Physics of Lipids

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“…3-Oxo-17a-pregn-4-ene 21,17-Carbolactone (20). To a solution of 350 mg (0.84 mmol) of 24 in 37 mL of acetonitrile were added 9 mL of water, 240 mg (1.8 mmol) of iV-chlorosuccinimide, and 321 mg (1.9 mmol) of silver nitrate, and the 33.81 (C-2), 35.39 (C-8), 35.63 (C-l), 35.81 3-Oxo-17a-pregna-l,4-diene 21,17-Carbolactone (25). To a solution of lactone 20 (150 mg, 0.44 mmol) in 7 mL of dry toluene was added 170 mg (0.73 mmol) of 2,3-dichloro-5,6dicyano-1,4-benzoquinone (DDQ), and the reaction mixture was heated at 100 °C for 5 h under argon atmosphere.…”

Section: Biological Results and Discussionmentioning

confidence: 99%

Steroidal Spiro-.gamma.-lactones That Inhibit 17.beta.-Hydroxysteroid Dehydrogenase Activity in Human Placental Microsomes

Sam¹,

Auger²,

Luu‐The³

et al. 1995

J. Med. Chem.

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The important enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17 beta-HSD for reducing the levels of active steroids, we found that steroidal spiro-gamma-lactones inhibit 17 beta-HSD activity. In this report, we describe the synthesis of 11 spiro-gamma-lactone analogs containing a steroidal C-18 or C-19 nucleus and compare their relative inhibitory effects on 17 beta-HSD activity in the human placenta microsomes that catalyze the interconversion of androgens and estrogens. To void the interaction of the cytosolic 17 beta-HSD activity that is specific for the interconversion of estrone and estradiol, we used 4-androstenedione as substrate. Analysis of the inhibitory effect exerted by these analogs on microsomal 17 beta-HSD activity indicates that spiro-gamma-lactones containing the C-18 nucleus are more potent inhibitors than C-19 nucleus analogs. The best inhibition was obtained with the phenolic spiro-gamma-lactone 7 (3-hydroxy-19-nor-17 alpha-pregna-1,3,5(10)-triene 21,17-carbolactone), which has an IC50 value of 0.27 microM, and was much lower than the competitive effect of the unlabeled substrate 4-androstenedione, which has an IC50 value of 1.40 microM. Preincubation with lactone 7 did not inactivate 17 beta-HSD activity. The results thus suggest that lactone 7 is a reversible in inhibitor. Lactone 7 is selective for microsomal 17 beta-HSD activity, as no inhibition was observed for cytosolic 17 beta-HSD activity.

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N-butyl, N-methyl, 11-[3′,17′ β-(dihydroxy)-1′,3′,5′(10′)- estratrien-16′ α-yl]-9(R/S)-bromo undecanamide: synthesis and 17β-HSD inhibiting, estrogenic and antiestrogenic activities

Cited by 32 publications

References 25 publications

Cerium(III) Chloride-Mediated Reactions of Sulfonamide Dianions

Cerium(III) Chloride-Mediated Reactions of Sulfonamide Dianions

Chemical synthesis of the 17-propanamide derivatives of stereoisomeric Δ14-17α- and 17β-estradiols: potential 17β-hydroxysteroid dehydrogenase inhibitors

Steroidal Spiro-.gamma.-lactones That Inhibit 17.beta.-Hydroxysteroid Dehydrogenase Activity in Human Placental Microsomes

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