470-03-1Relevant articles and documents
Concise large-scale synthesis of tomatidine, a potent antibiotic natural product
Boudreault, Pierre-Luc,Normandin, Chad
, (2021/10/12)
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.
Steroidal constituents isolated from the seeds of Withania somnifera
Iguchi, Tomoki,Kuroda, Minpei,Ishihara, Mai,Sakagami, Hiroshi,Mimaki, Yoshihiro
supporting information, p. 2205 - 2210 (2019/11/03)
A new withanolide glycoside (1), two new ergostanol glycosides (2 and 3), and a new furostanol glycoside (4), along with nine known steroidal derivatives (5–12) were isolated from the seeds of Withania somnifera. The structures of the new compounds were determined using spectroscopic analysis and hydrolysis. The cytotoxic activities of the isolated compounds were evaluated against Ca9-22 human gingival carcinoma cells, HSC-2 human mouth carcinoma cells, and HL-60 human promyelocytic leukemia cells. Only 12 exhibited cytotoxic activity against these cell lines with IC50 values of 0.38, 0.54, and 1.5 μM, respectively.
Gram-Scale Synthesis of Tomatidine, a Steroid Alkaloid with Antibiotic Properties Against Persistent Forms of Staphylococcus aureus
Normandin, Chad,Malouin, Fran?ois,Marsault, Eric
, p. 2693 - 2698 (2020/05/04)
We herein describe the first diastereoselective synthesis of the Solanum alkaloid tomatidine 1. The synthesis has been accomplished in 11 steps and 24.9 % overall yield (longest linear sequence). This methodology, which involves a convergent synthon insertion followed by a sequence of ring opening/nitrogen substitution/ring closing, allowed the generation of 1 on > 2 g scale. The synthetic challenge with the diastereoselective generation of the unusual spiroaminoketal moiety was solved through a combined azide reduction/addition sequence. The first diastereoselective synthesis of the phytosteroid yamogenin is also reported. Tomatidine has shown promising antibiotic properties against persistent forms of Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA). In particular, it possesses the unique ability to kill persistent forms of S. aureus and MRSA while simultaneously potentiating the antibiotic efficacy of aminoglycoside antibiotics against wild type strains of the bacteria.
Diosgenin derivatives, and pharmaceutical compositions thereof and application thereof
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Paragraph 0108-0110; 0113, (2019/01/24)
The invention relates to diosgenin derivatives. The structural formula of the diosgenin derivatives is as shown in a general formula (1) which is described in the specification. The invention also provides pharmaceutical compositions of the diosgenin derivatives and application thereof. According to the invention, systematic structural modification directed at double bonds at position 3 and position 5/6 of a lead compound is performed for the first time so as to synthesize a series of novel compounds; and the results of activity tests of the novel compounds at related targets show that most ofthe novel compounds have better activity than the activity of the lead compound and are very valuable for the treatment of neurodegenerative diseases. Thus, the diosgenin derivatives overcome defectsof conventional diosgenin derivatives and have important significance.
TIMOSAPONIN COMPOUNDS
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Paragraph 00250, (2013/10/22)
Provided herein are timosaponin compounds of Frmula I, II, IIΙ, I', II' and IIΙ', pharmaceutical compositions comprising the coumpounds, and processes of preparation thereof. Also provided are uses of said timosaponin compounds for preparing medicament for the treatment of diseases associated with beta-amyloid in hosts or subjects in need thereof.
Medicinal foodstuffs. IV. Fenugreek seed. (1): Structures of trigoneosides Ia, Ib, IIa, IIb, IIIa, and IIIb, new furostanol saponins from the seeds of indian Trigonella foenum-graecum L.
Yoshikawa, Masayuki,Murakami, Toshiyuki,Komatsu, Hajime,Murakami, Nobutoshi,Yamahara, Johji,Matsuda, Hisashi
, p. 81 - 87 (2007/10/03)
Six new furostanol saponins called trigoneosides Ia, Ib, IIa, IIb, IIIa, and IIIb were isolated from a medicinal foodstuff, fenugreek seed, the seed of Trigonella foenum-graecum L. (Leguminosae) originating from India, together with two known saponins, glycoside D and trigofoenoside A. The structures of trigoneosides Ia, Ib, IIa, IIb, IIIa, and IIIb were determined on the basis of chemical and physicochemical evidence as 26-O-β-D- glucopyranosyl-(25S)5α-furostane-2α,3β,22ξ,26-tetraol 3-O-[β-D- xylopyranosyl(1→6)]-β-D-glucopyranoside, 26-O-β-D-glucopyranosyl-(25R)- 5α-furostane-2α-3β,22ξ,26-tetraol 3-O-[β-D-xylopyranosyl (1→6)]-β-D- glucopyranoside, 26-O-β-D-glucopyranosyl-(25S)-5β-furostane-3β,22ξ,26- triol 3-O-[β-D-xylopyranosyl (1→6)]-β-D-glucopyranoside, 26-O-β-D- glucopyranosyl-(25R)-5β-furostane-3β,22ξ,26-triol 3-O-[β-D-xylopyranosyl (1→6)]-β-D-glucopyranoside, 26-O-β-D-glucopyranosyl-(25S)-5α-furostane- 3β,22ξ,26-triol 3-O-[α-L-rhamnopyranosyl(1→2)]-β-D-glucopyranoside, and 26-O-β-D-glucopyranosyl-(25R)-5α-furostane-3β,22ξ,26-triol 3-O-[α-L- rhamnopyranosyl (1→2)]-β-D-glucopyranoside, respectively.
Formation of ketones from alkyl nitrites in the solid state
Kinbara, Kazushi,Takezaki, Hiroshi,Kai, Akiyoshi,Saigo, Kazuhiko
, p. 217 - 218 (2007/10/03)
Alkyl nitrites selectively afforded the corresponding ketones upon photoirradiation in the solid state. It was suggested by the X-ray crystallographic analysis that the cavity in crystal and the initial conformation of the nitroso group had an influence on the yield of the ketones.
Steroidal saponins from Smilax officinalis
Bernardo, Robson Roney,Ventura Pinto, Antonio,Paz Parente, Jose
, p. 465 - 469 (2007/10/03)
Three new steroidal saponins were isolated from the rhizomes of Smilax officinalis. The structures of these saponins were established by extensive spectral data, hydrolysis and chemical correlation as sarsasapogenin 3-O-β- D-glucopyranosyl-(1 → 4)-[α-L-arabinopyranosyl-(1 → 6)]-β-D- glucopyranoside, neotigogenin 3-O-β-D-glucopyranosyl-(1 → 4)-[α-L- arabinopyranosyl-(1 → 6)]-β-D-glucopyranoside and 25S-spirostan-6β-ol 3- O-β-D-glucopyranosyl-(1 → 4)-[α-L-arabinopyranosyl-(1 → 6)]-β-D- glucopyranoside. Acid hydrolysis of the latter compound gave a sapogenin which has a new orientation of an hydroxyl on the steroidal skeleton. A route is proposed for the biogenesis of the latter sapogenin which is an uncommon steroidal aglycone.
STEROIDAL SAPONINS FROM THE TUBERS OF DICHELOSTEMMA MULTIFLORUM AND THEIR INHIBITORY ACTIVITY ON CYCLIC-AMP PHOSPHODIESTERASE
Inoue, Toshihiro,Mimaki, Yoshihiro,Sashida, Yutaka,Nakaido, Tamotsu,Ohmoto, Taichi
, p. 1103 - 1110 (2007/10/02)
Phytochemical examination of the tubers of Dichelostemma multiflorum led to the isolation of three new steroidal saponins together with two known saponins.The structures of the new compounds were determined by spectral data and a new chemical transformations to the (25R)-5α-spirostane-1β,3β-diol (brisbagenin) 1-O-3)-4-O-acetyl-α-L-arabonopyranoside>, brisbagenin 1-O-2)-O-3)>-4-O-acetyl-α-L-arabinopyranoside> and (22S,25S)-5α-spirostan-3β-ol 3-O-2)-O-3)>-O-β-D-glucopyranosyl-(1->4)-β-D-galactopyranoside).The known compounds were identified as desglucolanatigonin II and gitonin, with certain amounts of the corresponding C-25S isomers.Inhibitory activity of the isolated saponins and their derivatives on cAMP phosphodiesterase was evaluated to identify new compounds with medicinal potential.
