- Iridium-catalysed highly selective reduction-elimination of steroidal 4-en-3-ones to 3,5-dienes in water
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Steroidal 3,5-diene is an important structural motif in steroid drugs. In this report, an iridium-catalyzed reduction-elimination of readily available steroidal 4-en-3-ones is realized to prepare steroidal 3,5-dienes. At a low catalyst loading (S/C = 200), heating 4-en-3-ones in a water-mixed organic solvent with formic acid without inert atmosphere protection afforded the desired 3,5-dienes in moderate to excellent yields. In a gram-scale preparation, recrystallization is used instead of column chromatography to purify products. Excellent functionality tolerance and regioselectivity are featured. Structural moieties such as alkanols (primary, secondary and tertiary), esters (except for formate), tolylates, and ketones (endocyclic or exocyclic) are not affected. Surprisingly, the reduction-elimination only takes place at A-ring 4-en-3-ones. In addition, bicyclic 4-en-3-ones are also viable substrates. Synthetic applications of steroidal 3,5-dienes are demonstrated. Our method can also lead to steroidal 3,5-dienes-3-d (>99% d-incorporation) when DCO2D and D2O are used together.
- Li, Jide,Tang, Weiping,Ren, Demin,Xu, Jiaxi,Yang, Zhanhui
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p. 2088 - 2094
(2019/04/29)
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- Diosgenone synthesis, anti-malarial activity and QSAR of analogues of this natural product
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Solanum nudum Dunal steroids have been reported as being antimalarial compounds; however, their concentration in plants is low, meaning that the species could be threatened by over-harvesting for this purpose. Swern oxidation was used for hemisynthesis of diosgenone (one of the most active steroidal sapogenin diosgenin compounds). Eighteen structural analogues were prepared; three of them were found to be more active than diosgenone (IC50 27.9 μM vs. 10.1 μM, 2.9 μM and 11.3 μM). The presence of a 4-en-3-one grouping in the A-ring of the compounds seems to be indispensable for antiplasmodial activity; progesterone (having the same functional group in the steroid A-ring) has also displayed antiplasmodial activity. Quantitative correlations between molecular structure and bioactivity were thus explored in diosgenone and several derivatives using well-established 3D-QSAR techniques. The models showed that combining electrostatic (70%) and steric (30%) fields can explain most variance regarding compound activity. Malarial parasitemia in mice became reduced by oral administration of two diosgenone derivatives.
- Pabon, Adriana,Escobar, Gustavo,Vargas, Esteban,Cruz, Victor,Notario, Rafael,Blair, Silvia,Echeverri, Fernando
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p. 3356 - 3378
(2013/05/22)
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- Afromontoside. A New Cytotoxic Principle from Dracaena afromontana
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A new cytotoxic principle, steroidal saponin afromontoside (1), has been isolated from a methanolic extract of the twigs of Dracaena afromontana.It was shown to be (25R)-furost-5-ene-3β,22α,26-triol 26-O-α-L-rhamnopyranoside 3-O-(4)>-β-D-glucopyranoside) by spectral and chemical methods.The aglycone of afromotoside, diosgenin, as well as dihydrodiosgenin and severall structurally related compounds have been shown to be cytotoxic to cultured KB cells.
- Reddy, K. Sambi,Shekhani, Mohammed S.,Berry, David E.,Lynn, David G.,Hecht, Sidney M.
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p. 987 - 992
(2007/10/02)
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- REGIOSELECTIVE CLEAVAGE OF THE "E" RING IN DIOSGENIN
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Diosgenin, under a variety of acidic conditions, has been found to undergo an anomalous regioselective cleavage of the "E" ring affording a 16-keto derivative.
- Singh, Anil K.,Dhar, Durga N.
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p. 981 - 982
(2007/10/02)
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