Four new and other 4α-methylsterols in the seeds of Solanaceae

Four new 4α-methylsterols in the seeds of Solanaceae were identified as 31-norlanost-9(11)-enol, 24-methyl-31-norlanost-9(11)-enol, 4α,24-dimethylcholesta-7,24-dienol and 4α-methyl-24-ethylcholesta-7,24-dienol. The other 4α-methylsterols identified in the seeds were 31-norcycloartanol, 31-norcycloartenol, cycloeucalenol, 31-norlanost-8-enol, 31-norlanosterol, obtusifoliol, 4α,14α,24-trimethylcholesta-8,24-dienol, 4α-methylcholest-8-enol, lophenol, 24-methyllophenol, 24-ethyllophenol, gramisterol and citrostadienol. The distribution of these seventeen 4α-methyl- sterols in the seeds of eight species of the Solanaceae was determined.     

A hydroxygermacrene and other constituents from Pseudobrickellia brasiliensis

Pseudobrickellia brasiliensis afforded, in addition to known compounds, a new germacradiene derivative and a hydroxy-α-amyrin.     

Sesquiterpene lactones of Podanthus mitiqui

Ovatifolin and two new sesquiterpene lactones, deacetylovatifolin and arturin (1β-hydroxy-8β-angeloyloxy-eudesmane-4(15),11(13)-diene-6α,12-olide, have been isolated from stems and leaves of Podanthus mitiqui. Two of these compounds showed cytotoxic activity.     

Aromatic monoterpenes from Lavandula gibsonii

Three aromatic monoterpenes, not reported previously as natural products, together with ursolic acid, were isolated from Lavandula gibsonii. They were characterized as 3-hydroxy-α,α,4-trimethyl benzyl alcohol, 3-hydroxy- α,α,4-trimethyl benzyl methyl ether and 3-hydroxy-α,4-dimethyl styrene.     

Transformation of 23,24-bisnorchol-4-en-3-one-22-ol by Rhizopus arrhizus

The transformation of 23,24-bisnorchol-4-en-3-one-22-ol into 6β,11α,22-trihydroxy-23,24-bisnorchol-4-en-3-one by the fungus Rhizopus arrhizus has been shown to be dependent on the composition of the culture medium, with respect to yield of the triol. The transformation of the 22-alcohol to 6β,11α-dihydroxy-pregn-4-ene-3,20-dione is also reported.     

Two triterpenoid carboxylic acids from Acanthopanax trifoliatus

Two new triterpenoid carboxylic acids have been isolated from leaves of Acanthopanax trifoliatus and their structures elucidated as 3α, 11α-dihydroxylup-20(29)-en-28-oic acid and 30α, 11α,23-trihydroxylup-20(29)-en-28-oic acid by physical data and chemical transformations.     

Triterpenoids from the seedpods of Holarrhena curtisii King and Gamble

Two new hydroperoxy pentacyclic triterpenoids, 3β-hydroxy-11α-hydroperoxyolean-12-en-28-oic acid (1) and 3β-hydroxy-11α-hydroperoxyursan-12-en-28-oic acid (2), together with nine known triterpenoids, squalene (3), β-amyrin acetate (4), α-amyrin acetate (5), lupeol acetate (6), lupeol (7), lanosta-7,24-dien-3β-ol (8), cycloeucalenol (9), oleanolic acid (11) and ursolic acid (12), a known phytosterol, 24-methylenepollinastanol (10), and two known flavanols, (–)-catechin (13) and (–)-gallocatechin (14), were isolated from the methanolic extract of the fresh seedpods of Holarrhena curtisii. Their structures were determined by spectroscopic analysis (one and two dimensional nuclear magnetic resonance, high resolution electrospray ionization mass spectrometry and attenuated total reflectance-Fourier transform infrared spectroscopy). All compounds (except squalene) were evaluated for their in vitro α-glucosidase inhibitory activity. Compounds 1, 2, 11 and 12, which had a pentacyclic triterpenoid acid skeleton, showed a strong in vitro α-glucosidase inhibitory activity compared to that of the standard control, acarbose.     

An alternative explanation of hypertension associated with 17α-hydroxylase deficiency syndrome

The syndrome of 17α-hydroxylase deficiency is due to the inability to synthesize cortisol and is associated with enhanced secretion of both corticosterone and 11-deoxy-corticosterone (DOC). In humans, corticosterone and its 5α-Ring A-reduced metabolites are excreted via the bile into the intestine and transformed by anaerobic bacteria to 21-dehydroxylated products: 11β-OH-progesterone or 11β-OH-(allo)-5α-preganolones (potent inhibitors of 11β-HSD2 and 11β-HSD1 dehydrogenase). Neomycin blocks the formation of these steroid metabolites and can blunt the hypertension in rats induced by either ACTH or corticosterone. 3α,5α-Tetrahydro-corticosterone, 11β-hydroxy-progesterone, and 3α,5α-tetrahydro-11β-hydroxy-progesterone strongly inhibit 11β-HSD2 and 11β-HSD1 dehydrogenase activity; all these compounds are hypertensinogenic when infused in adrenally intact rats.Urine obtained from a patient with 17α-hydroxylase deficiency demonstrated markedly elevated levels of endogenous glycyrrhetinic acid-like factors (GALFs) that inhibit 11β-HSD2 and 11β-HSD1 dehydrogenase activity (>300 times greater, and >400 times greater, respectively, than those in normotensive controls). Thus, in addition to DOC, corticosterone and its 5α-pathway products as well as the 11-oxygenated progesterone derivatives may play a previously unrecognized role in the increased Na⁺ retention and BP associated with patients with 17α-hydroxylase deficiency.     

Triterpenoids from Salvia phlomoides, three new lupane derivatives

Three new triterpenoids have been isolated from the aerial parts of Salvia phlomoides. Their structures have been established by chemical and spectroscopic means and by correlation with known products as lupane-3β,11α,20-triol, 3β-acetoxy-lupane-11α,20-diol and 3-keto-lupane-11α,20-diol.     

Two 24-nor-triterpenoid carboxylic acids from acanthopanax trifoliatus

From Acanthopanax trifoliatus the new nor-triterpenes 24-nor-3α, 11α-dihydroxy-lup-20(29)-en-28-oic acid and 24-nor-11α-hydroxy-3-oxo-lup-20(29)-en-28-oic acid were isolated. Their structures were determined on the basis of spectroscopic data, X-ray analysis and chemical transformations.     

Structure of maritimin,a sesquiterpene lactone from artemisia maritima gallica

1-Keto-6β,7α,11β-H-selin-4(5)-en-6,12-olide, vulgarin and a new eudesmanolide, maritimin, were isolated from Artemisia maritima gallica. The structure and stereochemistry of this lactone have been determined by spectral studies and chemical transformations.     

3α,11α-Dihydroxylup-20(29)-ene-23,28-dioic acid from Schefflera octophylla

The structure of 3α,11α-dihydroxylup-20(29)-ene-23,28-dioic acid, a new triterpene isolated from Schefflera octophylla, has been determined by spectroscopic methods.     

Hypochaerin: a new sesquiterpene lactone from Hypochaeris setosus

Hypochaeris setosus contains desacetoxymatricarin, achillin, 1-hydroxy-6β,7α,11β-H-eudesm-4-en-6,12 olide, jacquinelin and hypochaerin, a new guaianolide, established as 3-oxo-4β,5α,6β,7α,11β-H-guai-1(2)-en-6,12 olide.     

3α-Hydroxy-multiflora-7,9(11)-dien-29α-oic acid,a new triterpene from Bryonia dioica

The structure of a new triterpene acid from the roots of Bryonia dioica is shown on the basis of chemical and spectroscopic evidence to be 3α-hydroxy-multiflora-7,9(11)-dien-29α-oic acid. This is the first report of a naturally occurring Δ^7,9(11) -multiflorene compound.     

Sesquiterpenes from severinia buxifolia

Three new sesquiterpenes were isolated from Severinia buxifolia, and identified as α-santalen-11-one, dihydro-α-santalen-12-one, and 12,13-epoxy-α-santalene, respectively. α-Photosantalol A, Δ^13,14-iso-α-santalol, α-santalene and (E)-5-(2,3-dimethyl-3-nortricyclyl)pent-3-en-2-one were also isolated and characterized.     

Synthesis,anti-diabetic evaluation and molecular docking studies of 4-(1-aryl-1H-1, 2, 3-triazol-4-yl)-1,4-dihydropyridine derivatives as novel 11-β hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitors

11-Beta-Hydroxysteroid dehydrogenase-1(11β-HSD1) inhibitors are one of the emerging classes of molecules to fight against diabetic complications. A novel series of 4-(1-substituted-1H-1,2,3-triazol-4-yl)-1,4-dihydropyridine derivatives were synthesized and evaluated for their anti-diabetic activity. Two compounds showed anti-diabetic activity very effectively. To clarify the mechanism of action of these compounds, the most potent compounds (5g and 5h) of the synthesized analogs were further studied by testing its 11-Beta Hydroxysteroid dehydrogenase-1 inhibitory activity through in vitro enzymatic experiments. The results showed that the 11β-HSD1 inhibitory activity of compounds 5g and 5h was stable and efficient. Molecular docking studies revealed compounds 5g (−9.758) and 5h (−8.495) to have a stable binding patterns to the human 11-Beta-Hydroxysteroid dehydrogenase-1.     

Factors affecting the adrenocorticotropic hormone stimulation of rabbit adrenal 17α-hydroxylase activity

Adrenocorticotropic hormone (ACTH)-stimulated 17α-hydroxylase activity of rabbit adrenal tissue has been shown to be associated with the subcellular fractions sedimented from 0.25 M sucrose at 33 000 × g for 60 min and at 105 000 × g for 60 min. The fraction sedimenting at 9000 × g for 20 min (mitochondria) contained the majority of the 11β-hydroxylase activity but also had a significant amount of 17α-hydroxylase activity. All subcellular 17α-hydroxylase activity showed an apparent preference for pregnenolone over progesterone. A 1 : 1 mixture of wholehomogenates of adrenal tissue from control and ACTH-stimulated rabbits incubated with[4-¹⁴C]pregnenolone synthesized as much 17α-hydroxylated corticosteroids as homogenate from the ACTH-stimulated tissue alone. However, the mixed homogenate synthesized only 1/4th–1/5th as much 17-deoxycorticosteroids as control, non-stimulated tissue, suggesting that the control tissue contained no inhibitor of 17α-hydroxylation, whereas ACTH-stimulated tissue may contain an inhibitor of 17-deoxycorticoid formation. 24-h dialysis of whole homogenates and subcellular fractions of adrenal tissue from control and ACTH-stimulated animals showed that 17α-hydroxylation was not activated in control tissue and somewhat inactivated in ACTH-stimulated tissue by this treatment. On the other hand, dialysis activated 17-deoxycorticoid formation by whole homogenates, but not in subcellular fractions, of both ACTH-stimulated and control adrenal tissue. Injection of 5 mg/kg cycloheximide prior to the first of 2 daily ACTH injections caused an average of 270 g body weight loss while not affecting the increase in adrenal weight effected by the ACTH. Adrenal tissue homogenates from cycloheximide injected animals produced only 50% as much 17α-hydroxycorticosteroids as homogenates of tissue from animals injected with ACTH alone and produced an amount of17-deoxycorticoids intermediate between homogenates of control and ACTH-stimulated tissue, suggesting the requirement of protein synthesis for 17α-hydroxylation stimulating activity of ACTH.     

Terpenes and steroids from leaves of Oxandra sessiliflora R. E. Fries

The EtOH extract from the leaves of Oxandra sessiliflora R. E. Fries (Annonaceae) was partitioned using hexane and CH₂Cl₂. After several chromatographic steps, caryophyllene oxide and spathulenol were isolated from hexane phase while, from CH₂Cl₂ phase, we isolated (E)-phytol, spathulenol, 4β,10α-dihydroxyaromadendrane, 1β,6α-dihydroxyeudesm-4(15)-ene, and 4α,7β,10α-trihydroxyguai-5-ene, the latter being a new sesquiterpene derivative. Additionally, a mixture of steroids (campesterol, sitosterol, and stigmasterol) was obtained from the CH₂Cl₂ phase. The isolated compounds were characterized by mass spectrometry and analysis of their ¹H and ¹³C NMR spectroscopic data, including bidimensional analysis.     

Phorbol derivatives from Sapium insigne

From an ether extract of the twigs and leaves of Sapium insigne four new diterpene esters were isolated. They were identified as 12-O-(2′E, 4′E-decadienoyl)-4-deoxy-16-hydroxyphorbol-13-acetate, 12-O-hexanoyl-4α-deoxy-phorbol-13-acetate, 12-O-hexanoyl-4α-deoxy-16-hydroxyphorbo-1-13-acetate and 12-O-dodecanoyl-4α-deoxy-16-hydroxyphorbol-13-acetate by spectroscopic and chemical methods.     

3α, 11α-Dihydroxy-23-oxo-lup-20(29)-en-28-oic acid from Acanthopanax trifoliatus

The new triterpene 3α,11α-dihydroxy-23-oxo-lup-20(29)-en-28-oic acid was isolated from Acanthopanax trifoliatus. Its structure has been determined on the basis of spectroscopic data and chemical transformations.