- Synthesis of clionamine B, an autophagy stimulating aminosteroid isolated from the sponge Cliona celata
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Clionamine B (2), an aminosteroid isolated from the marine sponge Cliona celata, has been synthesized starting from the plant sapogenin tigogenin (5). A key step in the synsthesis is the stereoselective introduction of the C-20 α-hydroxyl substituent via oxidation of a γ-lactone enolate with molecular oxygen. Synthetic clionamine B (2) strongly stimulated autophagy in human breast cancer MCF-7 cells.
- Forestieri, Roberto,Donohue, Elizabeth,Balgi, Aruna,Roberge, Michel,Andersen, Raymond J.
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- Concise large-scale synthesis of tomatidine, a potent antibiotic natural product
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Tomatidine has recently generated a lot of interest amongst the pharmacology, medicine, and biology fields of study, especially for its newfound activity as an antibiotic agent capable of targeting multiple strains of bacteria. In the light of its low natural abundance and high cost, an efficient and scalable multi-gram synthesis of tomatidine has been developed. This synthesis uses a Suzuki–Miyaura-type coupling reaction as a key step to graft an enantiopure F-ring side chain to the steroidal scaffold of the natural product, which was accessible from low-cost and commercially available diosgenin. A Lewis acid-mediated spiroketal opening followed by an azide substitution and reduction sequence is employed to generate the spiroaminoketal motif of the natural product. Overall, this synthesis produced 5.2 g in a single pass in 15 total steps and 15.2% yield using a methodology that is atom economical, scalable, and requires no flash chromatography purifications.
- Boudreault, Pierre-Luc,Normandin, Chad
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- Sarsasapogenin-structure-modified derivatives, pharmaceutical compositions thereof and applications of the compositions
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The invention relates to sarsasapogenin-structure-modified derivatives. The derivatives are characterized in that the structure formulas of the derivatives are shown as (I) and (II); pharmaceutical compositions of the derivatives and applications thereof are also provided; and many of the newly synthesized compounds show activity superior to activity of lead compounds through activity testing aiming at AD related targets. The compositions have high practical value for treating senile dementia. Defects of sarsasapogenin-structure-modified derivatives in the prior art are made up. The derivatives and the compositions are of great significance.
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Paragraph 0094-0097
(2017/07/20)
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- Epimerization of C-22 in (25R)- and (25S)-sapogenins
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Most of the naturally occurring steroidal sapogenins (C-23 non-substituted frameworks), possess an R configuration at the spiro C-22 center. Their C-22 epimers have become important targets in biological research. This paper describes a procedure to obtain 22S-spirostans from 22R-sapogenins and pseudosapogenin skeletons, without affecting the chirality at either C-25 or C-20. An optimal way to synthesize the pair of C-22 stereoisomers of 23-acetyldiosgenin is also reported. The latter was obtained from a 22,26-epoxycholestane or from 23-acetylfurostene compounds.
- Vias-Bravo, Omar,Merino-Montiel, Penlope,Romero-Lpez, Anabel,Montiel-Smith, Sara,Meza-Reyes, Socorro,Melndez, Francisco J.,Sandoval-Ramrez, Jess
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- Epimerization of C-22 in (25R)- and (25S)-sapogenins
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Most of the naturally occurring steroidal sapogenins (C-23 non-substituted frameworks), possess an R configuration at the spiro C-22 center. Their C-22 epimers have become important targets in biological research. This paper describes a procedure to obtain 22S-spirostans from 22R-sapogenins and pseudosapogenin skeletons, without affecting the chirality at either C-25 or C-20. An optimal way to synthesize the pair of C-22 stereoisomers of 23-acetyldiosgenin is also reported. The latter was obtained from a 22,26-epoxycholestane or from 23-acetylfurostene compounds.
- Vi?as-Bravo, Omar,Merino-Montiel, Penélope,Romero-López, Anabel,Montiel-Smith, Sara,Meza-Reyes, Socorro,Meléndez, Francisco J.,Sandoval-Ramírez, Jesús
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- The crystal structure of 3-epismilagenin acetate and 23-oxo-3-epismilagenin acetate
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The crystal structure together with unambiguous assignation of 1H and 13C NMR signals of 3-epismilagenin acetate 4 and 23-oxo-3-epismilagenin acetate 5 are described. Compound 4, crystallized as orthorhombic system a = 10.535(1) A, b = 13.775 (1) A, c = 18.347 (1) A, α = β = γ = 90°; with space group P2 1 2 1 2 1 ; while compound 5 crystallized as a monoclinic system a = 10.380(1) A, b = 7.327(1) A, c = 17.881(1) A, α = γ = 90°, β = 99.56(1)°, with a space group P2 1 . The presence a carbonyl group at C(23) in compound 5 produces a significant deviation from the chair conformation observed in compound 4. The effects of the side chain modifications on the puckering parameters derived from are discussed.
- MacIas-Alonso, Mariana,Esturau-Escofet, Nuria,Flores-Alamo, Marcos,Iglesias-Arteaga, Martin A.,Moreno-Esparza, Rafael
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experimental part
p. 1476 - 1482
(2012/06/15)
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- Synthesis of 5(6)-dihydro-OSW-1 by using the intact skeleton of tigogenin
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5(6)-Dihydro-OSW-1 (1), an analogue of OSW-1 with the potent anticancer activity, was synthesized by utilizing the intact skeleton of tigogenin in 13 steps in 9.0% overall yield. This synthesis demonstrated an effective and reasonable synthetic strategy for bioactive steroids with side chains as compared with their routine synthesis.
- Chen, Li-Jun,Xu, Qi-Hai,Huang, Hao,Lin, Jing-Rong,Tian, Wei-Sheng
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p. 3475 - 3477
(2008/02/10)
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- Cyanoglycosylation accompanied by ring-opening of spirostanols
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The reaction of 3-O-acetylsarsasapogenin (7), which has no hydroxyl group susceptible to glycosylation, with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (5) in the presence of a mixed catalyst, Hg(CN)2 and HgBr2, caused by clea
- Tobari, Akihiko,Miyamae, Hiroshi,Nagasawa, Akira,Koyanagi, Junichi,Kawase, Masami,Saito, Setsuo
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p. 1745 - 1764
(2007/10/03)
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- TRANSFORMATIONS OF SOLASODINE AND DERIVATIVES OF HECOGENIN BY CUNNINGHAMELLA ELEGANS
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Incubation of (25R)-5α-spirostane-3β,12β-diol (rickogenin) with the fungus Cunninghamella elegans led to the formation of (25R)-7β,12β-dihydroxy-5α-spirostan-3-one, (25R)-5α-spirostan-3β,7β,12β-triol and (25R)-5α-spirostan-3β,7α,12α-triol.Incubation of (25R)-5α-spirostan-3,12-dione (hecogenone) with the same fungus gave rise to (25R)-5α-spirostan-3,7,12-trione.When the (22R,25R)-spirosolane, solasod-5-en-3β-ol (solasodine) was incubated with C. elegans, solasod-5-ene-3β,7β-diol, solasod-5-ene-3β,7α-diol and 3β-hydroxysolasod-5-en-7-one were produced.In contrast, incubation of solasodine with Penicillium patulum gave solasod-4-en-3-one and the 6-methylsalicylic acid salt of solasodine.
- Patel, Asmita V.,Blunden, Gerald,Crabb, Trevor A.
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p. 125 - 134
(2007/10/02)
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- SYNTHESIS OF TIGOGENYL β-O-CELLOBIOSIDE HEPTAACETATE AND GLYCOSIDE TETRAACETATE VIA SCHMIDT'S TRICHLOROACETIMIDATE METHOD; SOME NEW OBSERVATIONS.
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In studying the synthesis of tigogenyl β-O-cellobioside 1 via the trichloroacetimidate method of Schmidt, cesium carbonate was found to be an efficient reagent for the synthesis of peracetylated disaccharide α-trichloroacetimidates.Zinc bromide was superior to BF3*Et2O for coupling these disaccharide α-trichloroacetimidates with the steroid tigogenin.
- Urban, Frank J.,Moore, Bernard S.,Breitenbach, Ralph
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p. 4421 - 4424
(2007/10/02)
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- Intramolecular Hydrogen Abstraction. Hypervalent Organoiodine Compounds, Convenient Reagents for Alkoxyl Radical Generation
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The photolyses of 5α-cholestane-3β,6β-diol 3-acetate (1), 5α-cholestan-2β-ol (4), 5α-cholestan-4β-ol (8), (20R)-pregn-5-ene-3β,20-diol 3-acetate (19), (20S)-pregn-5-ene-3β,20-diol 3-acetate (21), and dihydrotigogenin 3-acetate (25) in the presence of iodine and various hypervalent organoiodine compounds lead to alkoxyl radicals which undergo intramolecular hydrogen abstraction to produce, in most cases, 1,4-iodohydrins and tetrahydrofuran derivatives.
- Armas, Pedro de,Concepcion, Jose I.,Francisco, Cosme G.,Hernandez, Rosendo,Salazar, Jose A.,Suarez, Ernesto
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p. 405 - 411
(2007/10/02)
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- INTRAMOLECULAR HYDROGEN ABSTRACTION. IODOSOBENZENE DIACETATE, AN EFFICIENT AND CONVENIENT REAGENT FOR ALKOXY RADICAL GENERATION
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Photolysis of several hydroxy compounds in presence of iodosobenzene diacetate and iodine leads to alkoxy radical derivatives which undergo intramolecular hydrogen abstraction to produce cyclic ethers in good yields.
- Concepcion, Jose I.,Francisco, Cosme G.,Hernandez, Rosendo,Salazar, Jose A.,Suarez, Ernesto
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p. 1953 - 1956
(2007/10/02)
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- SEVEN-MEMBERED CYCLIC TRANSITION STATE IN THE ALKOXY-RADICAL INDUCED INTRAMOLECULAR HYDROGEN ABSTRACTION OF 26-HYDROXY-FUROSTANS
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The photolysis of 26-hydroxy-furostan (5) and (8) in the presence of Pb(OAc)4/I2 affforded spirostan sapogenins (4) and (7) respectively in 80percent yield.This cyclization takes place by an uncommon 1,6-hydrogen shift involving a 7-membered transition state as demonstrated by using specifically deuterium labeled compounds.
- Francisco, Cosme G.,Freire, Raimundo,Hernandez, Rosendo,Medina, Maria C.
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p. 4621 - 4624
(2007/10/02)
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- 14β-Hydroxysteroids, II. - The Prins Reaction of Lumihecogenin Acetate
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Photochemical rearrangement of hecogenin acetate (1) into the unsaturated aldehyde 5 followed by a Prins reaction leads efficiently to the 14β-hydroxysteroids 7a and 10a.The configuration of 7a, 10a, and 9a at C-13 and C-14 has been determined by chemical correlation and spectroscopically (1H-NMR, 13C-NMR, CD).
- Welzel, Peter,Janssen, Bernd,Duddeck, Helmut
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p. 546 - 564
(2007/10/02)
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- Separation of hecogenin-tigogenin mixtures
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A process for separating hecogenin-tigogenin mixtures which involves acetylating the mixed genins, then solvent recrystallization separation of the mixed genin acetates, crystallizing out hecogenin acetate from a non-polar solvent, tigogenin acetate from a polar solvent. A sequential sequence is contemplated to first recover the predominant genin, then the less-predominant genin. Preferred source materials are crude 5-25% sapogenin content acid hydrolyzates of Agave leaf juice. Specifically preferred is the acid hydrolyzate from fresh Agave leaf juice obtained prior to decortication.
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