Intramolecular cyclisation reactions of 5beta-cholan-24-amide, 3alpha-acetoxy-5beta-cholan-24-amide, and 3alpha-acetoxy-5beta-cholan-24-ol

Some intramolecular cyclisation reactions of bile acid derivatives have been studied. Photolysis of the N-iodo derivative of 5β-cholan-24-amide leads to the formation of the epimeric 5β-cholao24, 20?-lactones. The N-iodo derivative of 3α-acetoxy-5β-cholan-24-amide reacts similarly. Reaction of 3α-acetoxy-5β-cholan-24-ol with lead tetra-acetate and iodine gives the two 3α-acetoxy-20?, 24-oxido-5β-cholanes, two 3α-acetoxy-22e-iodo-20?,24-oxido-5β-cholanes, and the two 3α-acetoxy-21-iodo-20?,24-oxido-5β-cholanes. The two 3α-acetoxy-20?, 24-oxido-5β-cholanes are also obtained when 3d-acetoxy-5β-cholan-24-ol reacts with silver oxide and bromine.     

Towards an ecdysone synthesis. 20 -acetoxy-5 -pregna-2,7-dien-6-one

Pregnenolone (3β-hydroxy-5-pregnen-20-one) was converted to 20β-acetoxy-3, 5-cyclo-5α-pregnan-6-one by existing procedures. This compound was ring opened with bromine, and the resultant 3, 5-dibromide was subsequently rearranged to the 3, 7-dibromide. Dehydrohalogenation of the latter gave 20β-acetoxy-5α-pregna-2, 7-dien-6-one. This substance is of interest as intermediate for the synthesis of ecdysone.     

18-substituted steroids. part 4. a chemical synthesis of 3α, 18, 21-trihydroxy-5β-pregnan-20-one 18 → 20-hemiacetal (18-hydroxy-tetrahydro-doc)

3α, 18, 21-Trihydroxy-5β-pregnan-20-one 18 → 20-hemiacetal (18-hydroxy-tetrahydro-DOC) has been prepared from 3α-acetoxy-5β-pregnan-20-one by reduction to the 20β-alcohol, application of the ‘hypoiodite’ reaction [Pb(OAc)₄-I₂-hv] with subsequent steps leading to the 18-hydroxy-20-ketone (as hemiacetal), and C-21 acetoxylation [Pb(OAc)₄] followed by hydrolysis.     

Polar corticosteroids in human neonatal urine; Synthesis and gas chromatography-mass spectrometry of ring a reduced 6-hydroxylate corticosteroids

This report describes the synthesis of 3α, 6β, 11β, 17α, 21-pentahydroxy-5β-pregnane-20-one, 3α, 6β, 11β, 17α, 21-pentahydroxy-5α-pregnane-20-one, 3α, 6α, 11β, 17α, 21-pentahydroxy-5β-pregnane-20-one, 3α, 6α, 11β, 17α, 21-pentahydroxy-5α-pregnane-20-one, 3α, 6β, 17α, 21-tetrahydroxy-5β-pregnane-11, 20-dione, 3α, 6β, 17α, 21-tetrahydroxy-5α-pregnane-11, 20-dione, 3α, 6α, 17α, 21-tetrahydroxy-5β-pregnane-1 1, 20-dione and 3α, 6α, 17α, 21-tetrahydroxy-5α-pregnane-11, 20-dione.The gas chromatographic-mass spectrometric properties of these compounds are given. Proof of structure was accomplished using gas chromatography-mass spectrometry, microchemical reactions, optical rotatory dispersion and nuclear magnetic resonance spectroscopy.     

A steroid structure which refutes the isolation of C(17)-C(20) rotational isomers

Isolation of two C(17)-C(20) rotamers of 20-methyl-20-(2-hydroxy-ethoxy)-5-pregnene-3β, 17α-diol has been reported. X-Ray analysis of a diacetate derivative of one of the “rotamers” shows that the actual structure is 3β-acetoxy-17aα-(2-acetoxyethoxy)-17α,17aβ-dimethyl-D-homo-5-androsten-17β-ol (C₂₈H₄₄O₆). Thus, although this investigation refutes the existence of C(17)-C(20) rotamers, it suggests a possible new pathway for D-homo steroid synthesis.     

Two new triterpenoids from Rhodomyrtus tomentosa

Repetition of an investigation of the petrol extracts of Rhodomyrtus tomentosa has led to the isolation of two new triterpenoids, R₄ from the leaves and R₅ from the stems besides R₁, R₂, R₃ and the other known compounds already reported. R₁ and R₄ were proved to be 21α$\text{H}$-hop-22(29)en-3β,30-diol and 3β-hydroxy-21α$\text{H}$-hop-22(29)-en-30-al respectively, and R₂, R₃ and R₅ are 3β-acetoxy-11α,12α-epoxyoleanan-28,13β-olide, 3β-acetoxy-12α-hydroxyoleanan-28, 13β-olide and 3β-acetoxy-12-oxo-oleanan-28,13β- olide respectively. The ethanol extract of the leaves contained betulinic, ursolic and aliphitolic acids and that of the stems betulonic, betulinic and oleanolic acids.     

Bile acids XLII. Preparation of 5-alpha-cholestan-26-oic acids from kryptogenin

3β, 7α, 26-Triacetoxy-5α-cholestane was prepared from 25R-3β, 26-diacetoxy-5α-cholestan-7α-ol, and partially hydrolyzed with potassium carbonate in methanol-benzene. The three acetylated products thus obtained were characterized by thin layer and gas liquid chromatography, and mass spectrometry. By oxidation and alkaline hydrolysis, 3β, 7α-diacetoxy-5α-cholestan-26-ol was converted to 3β, 7α-dihydroxy-5α-cholestanoic acid. 7α, 26-Diacetoxy-5α-cholestan-3β-ol was characterized as indicated. The third product, 7α-acetoxy-5α-cholestane-3β, 26-diol was oxidized to 3-oxo-7α-acetoxy-5α-cholestanoic acid which was reduced catalytically and hydrolyzed to provide 3α, 7α-dihydroxy-5α-cholestanoic acids and its 3β-isomer. By comparison of the specific rotation of this sample of 3α, 7α-dihydroxy-5α-cholestanoic acid derived from 25R-kryptogenin with a similar product derived from arihydro-5α-cyprinol obtained from carp bile, the latter derivative appears to be primarily the 25S material.     

Steroids in newborns and infants identification by combined gas chromatography-mass spectrometry of the major steroids excreted by a newborn chimpanzee (Pan troglodytes)

The following steroids have been identified by combined gas chromatography-mass spectrometry in a urine specimen collected from a newborn chimpanzee; 5-androstene-3β, 17α-diol, 3β,16α (and 16β)-dihydroxy-5-androsten-17-one, 5-androstene-3β, 16α, 17β-triol, 5-androstene-3β, 16β, 17α-triol, 5-pregnene-3β, 20α-diol, 5-pregnene-3β, 20α, 21-triol, 3β,21-dihydroxy-5-pregnen-20-one, 3β, 16α-dihydroxy-5-pregnen-20-one, 5-Piegnene-3β, 16α,20α, 21-tetrol, 5-pregnene-3β,17α, 20ξ, 21-tetrol androstenetriolones and androstenetetrols.     

Inhibitors of sterol biosynthesis. Syntheses of 14α-alkyl substituted 15-oxygenated sterols

The chemical syntheses of a number of 14α-alkyl substituted 15-oxygenated sterols have been pursued to permit evaluation of their activity in the inhibition of the biosynthesis of cholesterol and other biological effects. Described herein are the first chemical syntheses of 14α-ethyl-5α-cholest-7-en-3β-ol-15-one, bis-3β,15α-acetoxy-14α-ethyl-5α-cholest-7-ene, 3β-acetoxy-14α-ethyl-5α-cholest-7-en-15β-ol, 14α-ethyl-5α-cholest-7-en-3β,15β-diol, 14α-ethyl-5α-cholest-7-en-3β,15α-diol, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15α-ol, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15β-ol, bis-3β,15α-hexadecanoyloxy-14α-ethyl-5α-cholest-7-ene, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15-one, 3α-benzoyloxy-14α-ethyl-5α-cholest-7-en-15-one, 14α-ethyl-5α-cholest-7-en-3α-ol-15-one, 14α-ethyl-5α-cholest-7-en-15-on-3β-yl pyridinium sulfate, 14α-ethyl-5α-cholest-7-en-15-on-3β-yl potassium sulfate (monohydrate), 14α-ethyl-5α-cholest-7-en-15-on-3α-yl pyridinium sulfate, 14α-ethyl-5α-cholest-7-en-15-on-3α-yl potassium sulfate (monohydrate), 3β-ethoxy-14α-ethyl-5α-cholest-7-en-15-one, 3β-acetoxy-14α-n-propyl-5α-cholest-7-en-15-one, 14α-n-propyl-5α-cholest-7-en-3β-ol-15-one, bis-3β, 15α-acetoxy-14α-n-propyl-5α-cholest-7-ene, 3β-acetoxy-14α-n-propyl-5α-cholest-7-en-15β-ol, 14α-n-propyl-5α-cholest-7-en-3β, 15α-diol, 14α-n-propyl-5α-cholest-7-en-3β, 15β-diol, 14α-n-butyl-5α-cholest-7-en-3β-ol-15-one, 3β-acetoxy-14-α-n-butyl-5α-cholest-7-en-15-one, bis-3β,15α-acetoxy-14α-n-butyl-5α-cholest-7-ene, 3β-acetoxy-14α-n-butyl-5α-cholest-7-en-15β-ol, 14α-n-butyl-5β-cholest-7-en-3β, 15β-diol, and 14α-n-butyl-5α-cholest-7-en-3β, 15α-diol.     

Intramolecular catalysis. VII: The nature of side chain shielding of the 12alpha-hydroxyl group of steroids

A series of 12α-hydroxy steroids with varying side chains was prepared, and their 24-hour acetylation yields were compared, l2α-Hydroxy-5β-pregnan-20-one ($\text{lb}$) was prepared from 3α, 12α-diacetoxy-5β~pregnan-20-one ($\text{2}$) and also by side chain degradation of 12α-acetoxy-5β-cholanoic acid ($\text{5d}$). 21-Benzyl-5β-pregnan-12α-ol ($\text{1g}$) was synthesized by hydrogenation of the 21-benzylidine derivative of ketone $\text{1b}$. 23-Pheny1-5β-norcholan-12α-ol ($\text{1k}$) was obtained by the Grignard reaction of 2-phenyl-ethylmagnesium bromide and ketone $\text{1b}$, dehydration, hydrogenation and hydride reduction; a similar sequence produced 20-methyl-5β-pregnan-12α-ol ($\text{lm}$). The acetylation results (Table 11) imply that branching at C-20 may be more significant for 12α-hydroxyl reactivity than side chain length or type. An additional compound with an unbranched side chain, 21-nor-5β-cholan-12α-ol ($\text{14}$), was synthesized by a Grignard reaction on the 21-bromo intermediate $\text{11b}$. Acetylation rates determined by glc indicate (Table 111) That compounds with unbranched side chains have 12α-hydroxyl groups about ten times as reactive as their analogs with 20-methyl groups.     

Eudesmane sesquiterpenoid lactones and abietane diterpenoids from Ajuga forrestii Diels

Four eudesmane sesquiterpenoid lactones (1–4) and seven abietane diterpenoids (5–11) were isolated from the whole plants of Ajuga forrestii. Among them, 3α-acetoxy-1α,8β-dihydroxyeudesm-7(11)-en-8,12-olide (1), 3α-acetoxy-1α-hydroxyl-eudesm-8,7(11)-dien-8,12-olide (2), 1α-acetoxy-8α-oxyethyl-2-oxo-eudesman-3,7(11)-dien-8,12-olide (3) and 2α,3β,11,12-tetrahydroxy-7β,20-epoxy-8,11,13-abietatriene (11) are novel compounds. The structures of compounds 1–11 were determined by spectroscopic analysis. Compound 2 exhibited weak cytotoxicity on HepG2 and MCF-7 cell lines.     

(22<Emphasis Type="Italic">R</Emphasis>,23<Emphasis Type="Italic">R</Emphasis>)-3β-hydroxy-22,23-epoxy-5α-ergost-8(14)-en-15-one: Improved synthesis and toxicity to MCF-7 cells

The chemical synthesis of (22R,23R)-3β-hydroxy-22,23-epoxy-5α-ergost-8(14)-en-15-one from (22A)-3β-acetoxy-5α-ergosta-7,14,22-triene was improved. The stages of obtaining and isomerization of (22A)-3β-acetoxy-14α15α-epoxy-5α-ergosta-7,22-diene were optimized. The introduction of (22R,23R)-epoxide cycle was carried out by alkaline treatment of intermediate (22S,23R)-3β,23-diacetoxy-22-iodo-5α-ergost-8(14)-en-15-one. In cells of human breast carcinoma MCF-7, (22R,23R)-3β-hydroxy-22,23-epoxy-5α-ergost-8(14)-en-15-one showed a high toxicity (TC₅₀ = 0.4±0.1 μM at 48-h incubation in serum-free medium).     

Secondary metabolites from two species of Pulicaria and their cytotoxic activity

Two new compounds, the sesquiterpene (1E,5E)-8β-acetoxy-4α-hydroxy-7βH-germacra-1(10),5-dien-14-oic acid (2), and a nor-sesquiterpene, (5E)-8β-acetoxy-4α-hydroxy-7βH-germacr-5-en-10-one (3), were isolated from Pulicaria canariensis ssp. lanata, along with ten known compounds, including the flavonoid 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (4). From Pulicaria burchardii, we isolated seven known compounds; the physical and spectroscopic data of the triterpenoid 3β-hydroxytaraxaster-20-en-30-al (1) are reported. The structures of compounds 1-3 were determined on the basis of HR-MS, and 1D- and 2D-NMR studies. The structure of 2 was corroborated by X-ray crystal diffraction. Cell viability experiments revealed that the semisynthetic flavonoid 4b was the most cytotoxic compound against human leukemia cells, and the cytotoxicity was caused by induction of apoptosis, as determined by microscopy of nuclear changes.     

Trichothecene mycotoxins from Fusarium sulphureum

Four mycotoxins isolated from moulded maize cultures of Fusarium sulphureum have been characterized as 3α,4β,15-triacetoxy-12,13-epoxytrichothec-9-ene, 4β,15-diacetoxy-3α-hydroxy-12,13-epoxytrichothec-9-ene, 15-acetoxy-3α,4β-dihydroxy-12,13-epoxytrichothec-9-ene and 4β-acetoxy-3α,15-dihydroxy-12,13-epoxytrichothec-9-ene.     

Inhibition of sterol biosynthesis by 14α-hydroxymethyl sterols

14α-Hydroxymethyl-5α-cholest-7-en-3β-ol (I) and 14α-hydroxymethyl-5α-cholest-6-en-3β-ol (II) have been prepared by chemical synthesis from 3β-acetoxy-7α,32-epoxy-14α-methyl-5α-cholestane. Compound I, previously shown to be efficiently convertible to cholesterol upon incubation with rat liver homogenate preparations, has been found to be a potent inhibitor of sterol synthesis in animal cells in culture. Compound I caused a 50% reduction of the levels of HMG-CoA reductase activity in cultures of L cells and fetal liver cells at concentrations of 3 × 10^?6 M and 8 × 10^?6 M, respectively. Compound II, the Δ⁶-analogue of I, caused a 50% suppression of the enzyme activity in the two cell types at even lower concentrations, 5 × 10^?7 M and 2 × 10^?6 M, respectively. Concentrations of I and II required to specifically inhibit sterol synthesis from acetate were similar to those required to suppress the levels of HMG-CoA reductase activity.     

Diterpenoids of Halimium viscosum

From the neutral fraction of the hexane extract of Halimium viscosum the following components were isolated; 7-labdene-3β,l5-diol, 15-acetoxy-7-labden-3β-ol and a new diterpene-lactone with a rearranged ent-labdane skeleton, 13S-ent-9, 1-friedo-labd-1(10)-en-15-acetoxy-2R,18-olide. From the non-saponifiable part, beside 7-labdene-3β, 15-diol and 7, 13E-labdadiene-3β, 15-diol, the new diterpene 8(17)-labdene-3β, 7α, 15-triol was extracted. The structures were elucidated by spectroscopic methods, correlations or synthesis.     

Hopane triterpenes from the scale insect pathogenic fungus Aschersonia calendulina BCC 23276

Two new hopane-type triterpenenes, 6α,15α,22-trihydroxyhopane (4) and 3β-acetoxy-6α,22-dihydroxyhopane (5), together with the known 6α,22-dihydroxyhopane (1, zeorin), 15α,22-dihydroxyhopane (2, dustanin), and 3β-acetoxy-15α,22-dihydroxyhopane (3) were isolated from the scale insect pathogenic fungus Aschersonia calendulina BCC 23276. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data.     

Metabolism of progesterone by chorionic cells of the early sheep conceptus invitro

Progesterone-4-¹⁴C was extensively metabolized during incubation with dispersed trophoblast prepared from chorionic membranes of the 21-day sheep conceptus. Of the metabolites formed, 17,20α-dihydroxypregn-4-en-3-one, 20α-hydroxypregn-4-en-3-one, 20(β-hydroxypregn-4-en-3-one, 5α-pregnane-3α,17,20α-triol, 5β-pregnane-3ga, 17,20α-triol, 5β-pregnane-3g,20α-diol, 3β-hydroxy-5α-pregnan-20-one, 3α-hydroxy-5β-pregnan-20-one, 20β-hydroxy-5β-pregnan-3-one, 5α-pregnane-3,20-dione and 5β-pregnane-3,20-dione were identified. These findings indicate that the sheep conceptus acquires extensive steroid metabolizing capability very early in pregnancy.     

Isolation of 20 alpha and 20 beta 5 beta-pregnane-3 alpha,17 alpha,20,21-tetrol (hexahydro-Reichstein's compound-S) in a case of congenital adrenal hyperplasia

5β-Pregnane-3α, 17α, 20α, 21-tetrol (l) and 5β-pregnane-3α, 17α 20β, 21-tetrol (II) have been isolated and identified from the urine of a girl with congenital adrenal hyperplasia. The total 5β-pregnane-3α, 17α, 20(α+β),21-tetrol consisted of 60% of I and 40% of II. The final identity of the compounds was established by gas chromatography — mass spectrometry. The mass spectra of the two trimethylsilyl isomers were closely related to each other in contrast to the spectra of five other pairs of C₂₁-C-20(α and β)-hydroxy steroid-trimethylsilyl-ethers. The mass spectra of free I and II also exhibited many common features, but were less similar to each other than their trimethylsilyl derivatives.     

Enzymatic isomerization (Δ7 → Δ8) of the nuclear double bond of 14α-alkyl substituted sterol precursord of cholesterol

The catalysis by rat liver microsomes under anaerobic conditions, of the conversion of [3α-³H]14α-methyl-5α-cholest-7-en-3β-ol and of [2,4-³H]14α-hydroxymethyl-5α-cholest-7-en-3β-ol to labeled 14α-methyl-5α-cholest-8-en-3β-ol and 14α-hydroxymethyl-5α-cholest-8-en-3β-ol, respectively, has been demonstrated. This finding is of importance in evaluating past research in this area and in consideration of pathways and mechanisms involved in enzymatic removal of carbon atom 32 of 14α-methyl sterols. Also described herein are syntheses of [2,4-³H]14α-hydroxymethyl-5α-cholest-7-en-3β-ol and 3β-acetoxy-14α-methyl-5α-cholest-8-ene.