55289-59-3Relevant academic research and scientific papers
Steroidal spiro-γ-lactones that inhibit 17β-hydroxysteroid dehydrogenase activity in human placental microsomes
Sam,Auger,Luu-The,Poirier
, p. 4518 - 4528 (1995)
The important enzyme 17β-hydroxysteroid dehydrogenase (17β-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17β- HSD for reducing the levels of active steroids, we found that steroidal spiro-γ-lactones inhibit 17β-HSD activity. In this report, we describe the synthesis of 11 spiro-γ-lactone analogs containing a steroidal C-18 or C-19 nucleus and compare their relative inhibitory effects on 17γ-HSD activity in the human placenta microsomes that catalyze the interconversion of androgens and estrogens. To avoid the interaction of the cytosolic 17β-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 17β-HSD activity indicates that spiro-γ- lactones containing the C-18 nucleus are more potent inhibitors than C-19 nucleus analogs. The best inhibition was obtained with the phenolic spiro- γ-lactone 7 (3-hydroxy-19-nor-17α-pregna-1,3,5(10)-triene 21,17- carbolactone), which has an IC50 value of 0.27 μM, and was much lower than the competitive effect of the unlabeled substrate 4-androstenedione, which has an IC50 value of 1.40 μM. Preincubation with lactone 7 did not inactivate 17β-HSD activity. The results thus suggest that lactone 7 is a reversible inhibitor. Lactone 7 is selective for microsomal 17β-HSD activity, as no inhibition was observed for cytosolic 17β-HSD activity.
Processes for preparation of 3-keto-7alpha-alkoxycarbonyl-delta-4,5- steroids and intermediates useful therein
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Page 199, (2008/06/13)
Multiple novel reaction schemes, novel process steps and novel intermediates are provided for the synthesis of epoxymexrenone and other compounds of Formula I wherein:-A-A- represents the group -CHR4-CHR5- or -CR4=CR5- R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano, varyloxy;R1 represents an alpha-oriented lower alkoxycarbonyl or hydroxyalkyl radical;-B-B- represents the group -CHR6-CHR7- or an alpha- or beta- oriented group: where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy; andR8 and R9 are independently selected from the group consisting of hydrogen, hydroxy, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy, or R8 and R9 together comprise a carbocyclic or heterocyclic ring structure, or R8 or R9 together with R6 or R7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring.
Intramolecular condensation of steroidal 17α-formyl-17β-acetates: Synthesis of 14-hydroxymethyl-3-oxo-19-nor-17α-pregn-4-ene-21,17-carbolactone
Bull,Steer
, p. 6907 - 6910 (2007/10/02)
Intramolecular condensation of steroidal 17β-acetoxy-17α-carbaldehydes offers a synthetic route to 19-nor-17,17-spirolactones
A Direct Synthesis of γ-, δ-, and ε-Lactones Utilizing SmI2-induced Barbier-type Reaction in the Presence of Hexamethylphosphoric Triamide (HMPA)
Otsubo, Kenji,Kawamura, Kisa,Inanaga, Junji,Yamaguchi, Masaru
, p. 1487 - 1490 (2007/10/02)
By using an efficient reduction system of SmI2-THF-HMPA, the coupling reaction of β-, γ-, or δ-bromoesters with carbonyl compounds was completed within a minute at room temperature affording γ-, δ-, or ε-lactones, respectively, in good yields.Cp2ZrCl2 was also found to be effective for the coupling with ketones.
SmI2-INDUCED REDUCTIVE CROSS-COUPLING OF CARBONYL COMPOUNDS WITH α,β-UNSATURED ESTERS
Otsubo, Kenji,Inanaga, Junji,Yamaguchi,Masaru
, p. 5763 - 5764 (2007/10/02)
Reductive cross-coupling of carbonyl compounds with α,β-unsaturated esters by SmI2 to γ-lactones was highly accelerated by the addition of hexamethylphosphoric triamide (HMPA).
Silicon in Synthesis. 10. The (Trimethylisilyl)allyl Anion: A β-Acyl Equivalent for the Conversion of Aldehydes and Ketones into γ-Lactones
Ehlinger, Ed,Magnus, Philip
, p. 5004 - 5011 (2007/10/02)
The (trimethylsilyl)allyl anion reacts with a number of ketones and aldehydes to give adducts 11-21, resulting from the γ mode of ambident reactivity.These adducts were epoxidized to provide the corresponding α,β-epoxysilanes 23-31.Treatment of the epoxysilanes with methanol in the presence of boron trifluoride etherate gave the lactol methyl ethers 32-39.Jones oxidation of the lactol methyl ethers gave γ lactones 40-45.Addition of bromine to the 4-hydroxy vinylsilane derivative 19 gave oxetane 47 which was converted into the compounds 49, 50, and 51.Application of the (trimethylsilyl)allyl anion, as its zinc counterion, to the synthesis of 17-spirosteroidal lactones is described.
SILICON IN SYNTHESIS: USE OF THE HIGHLY NUCLEOPHILIC TRIMETHYLSILYLALLYL ANION FOR THE SYNTHESIS OF STEROIDAL 17-SPIRO-γ-LACTONES
Ehlinger, Ed,Magnus, Philip
, p. 11 - 14 (2007/10/02)
Trimethylsilylallylzinc chloride 2 (M = ZnCl) reacts with 17-ketosteroids to give adducts 4 that can be converted into 17-spirolactones.
