Organic synthesis of 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine and its effect on the induction of apoptosis in normal human lung fibroblasts.

Background /objective: The phospholipid 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine (PE) comprises two fatty acid chains: glycerol, phosphate, and ethanolamine. PE participates in critical cellular processes such as apoptosis and autophagy, which places it as a target for designing new therapeutic alternatives in diseases such as pulmonary fibrosis. Therefore, this study aimed obtain PE through a six-step organic synthesis pathway and determine its biological effect on apoptosis induction in normal human lung fibroblasts (NHLF).

(23,23 ,25)-23,26-Ep-oxy-23-ethyl-furost-20(22)-en-3β-ol.

The title compound, CHO, is a steroid synthesized through a rearrangement of a sarsasapogenin derivative in acidic medium. The newly formed ring is a tetra-hydro-2-pyran heterocycle substituted by two methyl groups placed in equatorial positions. This ring displays a chair conformation, while di-hydro-furan ring , to which it is bonded, has an envelope conformation.

Prediction on the PI3K/AKT/mTOR Pathway of the Antiproliferative Effect of in Breast Cancer Models.

The search for new cancer treatments from traditional medicine involves developing studies to understand at the molecular level different cell signaling pathways involved in cancer development. In this work, we present a model of the PI3K/Akt/mTOR pathway, which plays a key role in cell cycle regulation and is related to cell survival, proliferation, and growth in cancer, as well as resistance to antitumor therapies, so finding drugs that act on this pathway is ideal to propose a new adjuvant treatment. The aim of this work was to model, simulate and predict using the Big Data-Cellulat platform the possible targets in the PI3K/Akt/mTOR pathway on which the extract acts, as well as to indicate the concentration range to be used to find the mean lethal dose in experiments on breast cancer cells.

,'-Di-cyclo-hexyl--(phthaloylglyc-yl)urea.

The mol-ecular structure of the title compound {systematic name: 1,3-di-cyclo-hexyl-1-[2-(1,3-dioxo-2,3-di-hydro-1-isoindol-2-yl)acet-yl]urea}, CHNO, derived from ,'-di-cyclo-hexyl-urea, shows that the tertiary N atom substituted by a cyclo-hexyl and phthaloylglycyl groups adopts a perfectly planar geometry (bond-angle sum = 360.0°). In the same way as for ,'-di-cyclo-hexyl-urea, the extended structure of the title compound features N-H⋯O hydrogen bonds, which generate chains of mol-ecules running in the [001] direction.

Synthesis and biological in vitro evaluation of the effect of hydroxyimino steroidal derivatives on breast cancer cells.

Breast cancer is the most common cause of cancer death in women, according to Global Cancer Observatory. This fact forces scientists to continue in the search for effective treatments against this aggressive type of cancer. Breast cancer frequently metastasizes to other organs, most often the bones, lungs, and liver.

Azasteroids from diosgenin: Synthesis and evaluation of their antiproliferative activity.

In this work, we report the synthesis of two new azasteroids through the modification of the A and B rings of diosgenin 1. The 4-azasteroid derivative 12 was prepared in three steps using the α,β-insaturated-3-keto compound 11 as a precursor, which was first oxidized with KMnO/KIO followed by an oxidative cleavage of ring A, and subsequently cyclized with an ammonium salt, under focused microwave irradiation for a short time of 3 min. A second azasteroid was synthesized, for which the key step was the Beckmann rearrangement of ring B of the oxime 16, affording the lactam-type enamide 17 in good yield.

Diosgenin-3,6-dione: second polymorph in space group 222.

The title steroid, [(25)-spirost-4-en-3,6-dione, CHO], is obtained by oxidation of diosgenin, using the Jones reagent (CrO/HSO). The crystal structure was previously reported in space group 222, but nonetheless with the wrong absolute configuration and omitting positions for H atoms [Rajnikant (2000 ▸). , , 101-110].

Mesoscale Assembly of Bisteroidal Esters from Terephthalic Acid.

A new series of bisteroidal esters was synthesized using a spacer group, sterols and sapogenins as substrates. Steroidal dimers were prepared in high yields employing diesters of terephthalic acid as linkages at the 3β, 3'β steroidal positions. In all attempts to crystallize bisteroids, it was observed that the compounds tended to self-organize in solution, which was detected when employing various solvent systems.

Mimicking natural phytohormones. 26-Hydroxycholestan-22-one derivatives as plant growth promoters.

26-Hydroxycholestan-22-one derivatives with oxygenated functions in the rings A and/or B were successfully synthesized from diosgenin. After the modifications of rings A and B, the spiroketal side chain was selectively opened through a Lewis acid mediated acetolysis to afford the cholestane derivatives. These compounds incorporate pharmacophores, which mimic the activity of natural phytohormones and show high growth promoting activity in Mexican rice cultivars using the rice lamina inclination test.

Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines.

Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report the synthesis and in vitro antitumor activity of two steroidal oxime compounds on cervical cancer cells.

Large-scale green chemical synthesis of adjacent quaternary chiral centers by continuous flow photodecarbonylation of aqueous suspensions of nanocrystalline ketones.

To demonstrate the ease of scale-up and synthetic potential of some organic solid state reactions, we report the synthesis, crystallization, and solid state photochemistry of acyclic, homochiral, hexasubstituted (+)-(2R,4S)-2-carbomethoxy-4-cyano-2,4-diphenyl-3-pentanone 1. We demonstrate that solid state photodecarbonylation of (+)-(2R,4S)-1 affords (+)-(2R,3R)-2-carbomethoxy-3-cyano-2,3-diphenyl-butane 2 with two adjacent stereogenic, all-carbon substituted quaternary centers, in quantitative chemical yield and 100% diastereoselectivity and enantiomeric excess. The efficient multigram photodecarbonylation of (+)-(2R,4S)-1 as a nanocrystalline suspension in water using a continuous flow photoreactor shows that the large-scale synthesis of synthetically challenging compounds using photochemical synthesis in the solid state can be executed in a remarkably simple manner.

Synthetic pathway to 22,23-dioxocholestanic chain derivatives and their usefulness for obtaining brassinosteroid analogues.

Recognizing the functionality of the pentacyclic steroidal derivative 7a as important synthon to obtain new brassinosteroid analogs, we have accomplished the derivatization of hecogenin, a sapogenin from the 25R serie containing a carbonyl group at C-12, to a 22,23-dioxocholestanic chain derivative. Starting from hecogenin acetate (5a) or hecogenin tosylate (5b), we obtained two pentacyclic derivatives (7a and 7b) which were subjected to an oxidation reaction on the double bond at C-12(23) to obtain a 22,23-dioxocholestanic chain, with the regeneration of the carbonyl group at C-12. Reduction of the carbonyl groups lead to the 20-epi-12,23-dihydroxy-22-oxo system 11a-b.

(25R)-6α-Hy-droxy-5α-spiro-stan-3β-yl tosyl-ate.

The title steroid, C34H50O6S, is an inter-mediate on the synthetic route between diosgenin and brassinosteroids, which possess the A ring modified with the 2α,3α-diol functionality. The polycyclic spiro-stan system has the expected conformation, with six-membered rings adopting chair forms and the five-membered rings envelope forms (flap atoms are the methine C atom in the C/D-ring junction and the spiro C atom connecting rings E and F). The 3β-tosyl-ate group is oriented in such a way that S=O bonds are engaged in inter-molecular hydrogen bonds with O-H and C-H donors.

Diosgenone: a second P2(1) polymorph.

Diosgenone [(20S,22R,25R)-spirost-4-en-3-one, C(27)H(40)O(3)] has been proposed as a new therapeutic alternative for the treatment of malaria. The first X-ray structure report for diosgenone was by Piro et al. [(2002).

Diosgenin hemihydrate.

Diosgenin [or (22R,25R)-spirost-5-en-3β-ol] is the starting material of the Marker degradation, a cheap semi-synthesis of progesterone, which has been designated as an Inter-national Historic Chemical Landmark. Thus far, a single X-ray structure for diosgenin is known, namely its dimethyl sulfoxide solvate [Zhang et al. (2005 ▶).

Stereospecific synthesis of new steroidal isoxazoles in dry media.

An easy and fast procedure was developed for one-pot synthesis of steroidal isoxazoles starting from 23-acetylsapogenins derivatives in presence of P2O5/SiO2 in dry media under microwaves irradiation is described. Substrates of the 25S and 25R series were used as raw materials, establishing that this new methodology is applicable to both series.

(R)-1-Phenyl-ethyl-ammonium trifluoro-acetate.

In the crystal structure of the title salt, C(8)H(12)N(+)·C(2)F(3)O(2) (-), all of the ammonium H atoms serve as donors for hydrogen bonds to carboxyl-ate O atoms, forming an R(4) (3)(10) ring motif based on two cations and two anions. Since both cations and anions act as inter-ion bridging groups, R(10) rings aggregate in a one-dimensional supra-molecular network by sharing the strongest N-H⋯O bond. Edge-sharing motifs lie on the twofold screw axis parallel to [010], and anti-parallel packing of these 2(1)-column structural units results in the crystal structure.

(20S,2''S)-20-[4'-(3''-Hydroxy-2''-methyl-prop-yl)-3'-methylisoxazol-5-yl]-5β-preg-nan-3β,16β-diol.

The title steroidal compound, C(29)H(47)NO(4), was prepared in a one-pot reaction starting from a sarsasapogenin derivative of known configuration. The isoxazole heterocycle is oriented towards the α face of the steroid nucleus and, although fully functionalized on C atoms, does not provoke steric hindrance with the adjacent D ring. The absolute configuration observed for chiral centers is as expected, and shows that no epimerization occurred in the precursors.

The zwitterion (23'E)-(23R,25S)-23-[1-(oxidoiminio)eth-yl]-5β-spiro-stan-3β-yl acetate.

The title steroidal compound, C(31)H(49)NO(5), resulted from the selective oximation of (23R)-23-acetyl-sarsasapogenin acetate. One- and two-dimensional (1)H and (13)C NMR spectra, as well as IR data, are in agreement with the presence of a ketoxime group at C-23. However, recrystallization in slightly acidic media affords the title compound in the rare zwitterionic oxime form, as a consequence of migration of the hydr-oxy H atom to the N atom in the oxime group.

(E)-(25S)-23-Acetyl-5β-furost-22-ene-3β,26-diol.

The title steroid, C(29)H(46)O(4), is a furostene derivative with a C=C double-bond length of 1.353 (3) Å and an E configuration. The side chain is oriented toward the α face of the A-E steroidal nucleus and presents a disordered terminal CH(2)-OH group [occupancies for resolved sites are 0.