Synthesis of digitoxigenin by remote functionalization

Treatment of a 21-hydroxy-20-keto steroid with the mixed anhydride of trifluoroacetic acid—diethylphosphonoacetic acid leads directly to cardenolides by an intramolecular Horner-Emmons reaction. Photolysis of 3β-acetoxy-5β,14α-card-20(22)-enolide and iodobenzenedichloride in benzene solution then yields 3β-acetoxy-5β-carda-14,20(22)-dienolide (β-anhydrodigitoxigenin acetate).     

Opposid,vermutliche Struktur. Glykoside und Aglykone, 302. Mitt.

The hypothetical structure 1 is proposed for opposide (C₂₉H₄₄O₁₁), a new glycoside from the seeds of Acokanthera oppositifolia (LAM.) CODD. Opposide is derived from the new aglycone gratogenin, which is most probably the 1β, 3β, 5β, 11α, 14β-pentahydroxy-card-20:22-enolide ( 8 ) (C₂₃H₃₄O₇) and which is bound glycosidically through position 3 to the α-pyranosidic form of 6-desoxy-L-talose. The hydrolysis of opposide by HCl in acetone gave an anhydrogenin (C₂₃H₃₂O₆) instead of the intact aglycone. In analogy to the reaction sequence observed by VOLPP and TAMM for ouabagenin, the structure of the anhydrogenin is deduced to be that of a 3β, 5β, 14β-trihydroxy-1α, 11α-epoxy-card-20:22-enolide ( 6 ). The above mentioned structures are based on the course of acetylation and especially on NMR.-spectra.     

2α, 3β, 19-Triacetoxy-14α-hydroxy-5α-card-20:22-enolid: Teilsynthese. Zusätzlicher Beweis für die Struktur des Calotropagenins. Glykoside und Aglykone, 324. Mitteilung

Coroglaucigenin, which is known to be a 3β, 14β, 19-trihydroxy-5α-card-20: 22-enolid, was transformed into 2α, 3β, 19-triacetoxy-14β-hydroxy-5α-card-20 : 22-enolid. The latter was identical with the known tri-O-acetyl-19-dihydro-calotropagenin. The structure of calotropagenin ( 1 ) is thus established through an independent way.     

Glycosylation of cardenolides. VIII. Structures of the by-products of the synthesis by the orthoester method of strophanthidol rhamnosides

The by-products formed in the preparation of strophanthiodol 19-rhamnoside and 3, 19-bisrhamnoside by the orthoester method are 3β,5-dihydroxy-8,19-epoxy-5β,14β, 17α-card-20(22)-enolide and its 3-α-L-rhamnoside. 3β,5-Dihydroxy-8,19-epoxy-5β, 14α,17β-card-20(22)-enolide has been obtained by the action of a solution of HBr in nitromethane on strophanthidol.     

"Alpha"-, "beta"- and "delta"-anhydrodigitoxigenin

The syntheses of 3β-hydroxy-5β-carda-14, 20:22-dienolide (= «β»-anhydro-), 3β-hydroxy-5β-carda-8:14, 20:22-dienolide (= «α»-anhydro-) and «δ»-anhydro-digitoxigenin (= probably 3β-hydroxy-5β, 14β-carda-8, 20:22-dienolide) by the best ways known to date, have been described. «δ»-Anhydro-digitoxigenin represents the thermodynamically most stable isomer. In this isomer the double bond in position 8 is unaffected by hydrogenation with Pt in acetic acid; with perbenzoic acid an epoxide results from which, on hydrogenation, the double bond can be regenerated in its original position. Analogous reactions are known to occur in the 8:14-epoxides.     

Nigrescigenin,Identifizierung mit Sarmentosigenin A Glykoside und Aglykone, 281. Mitteilung

“Sarmentosigenin A” has been identified with nigrescigenin. The latter is the older and thus valid name for this 3β, 5β, 11α, 14β-tetrahydroxy-19-oxo-card-20:22-enolide.     

Sarverogenin,vermutliche Struktur. Glykoside und Aglykone, 314. Mitteilung

Sarverogenin is most probably a 3β, 11β, 14β-trihydroxy-7, 8β-epoxy-12-oxo-5β-card-(20:22)-enolide ( 3 ). This follows from IR., NMR., and mass spectra together with former chemical results.     

Cardiac glycosides of Erysimum contractum. II

The structure of a new cardiac glycoside isolated from the seeds ofErysimum contractum has been established. The glycoside, which has been called nigrescigenin digilanidobioside is 3β,5,11α,14-tetrahydroxy-19-oxo-5β,14β-card-20(22)-enolide 3-O-(4-O-β-D-glucopyranosyl-β-D-digitoxopyranoside).     

Withasteroids ofPhysalis. VII. 14α-Hydroxyixocarpanolide and 24,25-expoxywithanolide D

Two new withasteroid have been isolated fromPhysalis angulata L. — 14α-hydroxyixocarpanolide and 24,25-epoxywithanolide D. 14α-hydroxyixocarpanolide — C₂₈H₄₀O₇, mp 245–250°C (from methanol), [α] _D ²⁰ +29±2° (chloroform). 24,25-Epoxywithanolide D — C₂₈H₃₈O₇, mp 257–261°C (from methanol, [α] _D ²⁰ +23±2° (chloroform). On the basis of its UV, IR, CD, mass, and¹H and¹³C NMR spectra the structure of 5α,14α,20R-trihydroxy-1-oxo-6α,7α-epoxy-22R-2itha-2-enolide is suggested for 14α-hydroxyixocarpanolide. On the basis of spectral characteristics and the preparation of 4β-acetoxy and 4-oxo derivatives of 24,25-epoxywithanolide D, the structure of 4β,20R-dihydroxy-1-oxo-5β,6β;24S,25S-diepoxy-22R-witha-2-enolide is proposed for it.     

Cardenolides ofStrophanthus kombe III. 17α-Strophadogenin

17α-Strophadogenin, which is 3β,5,14,16β-tetrahydroxy-19-oxo-5β,14β-card-17βH-20(22)-enolide has been obtained in the pure form for the first time and has been studied.     

Zur Stereochemie der Epoxycardanolide (Isogenine)

The stereochemistry of the epoxycardanolides 8 , 21 , 24 and 33 , derived from digitoxigenin ( 1 ), digoxigenin ( 15 ), 3β, 14, 15β-trihydroxy-5β, 14β-card-20(22)-enolide ( 23 ) and gitoxigenin ( 27 ) respectively, is discussed on the basis of NMR. data. In the case of 1 and 15 the absolute configuration of the chiral centres C(20) and C(21) is assigned. Treatment of the cardenolides with KOH in methanol gave on dilution with methanol and subsequent acidification a number of acetal derivatives, the properties of which are described.     

Analogs of ecdysteroids with a tetrasubstituted Δ<Superscript>8,14</Superscript>-bond

By hydrogenation of (20R,22R)-6α,14α,25-trihydroxy-and (20R,22R)-6β,14α,25-trihydroxy-2,3:20,22-bis(isopropylidenedioxy)-5α-cholest-7-enes on a catalyst (Raney nickel) the corresponding (5α,6α)-and (5β,6β)-epimers of previously unknown Δ^8,14-6-hydroxy derivatives of ecdysteroids were synthesized.     

Cardenolide and pregnane derivatives from the roots of Trachycalymma fimbriatum (Weimark) Bullock. Glycosides and aglycones. 322

The roots of Trachycalymma fimbriatum (WEIMARCK ) BULLOCK contain both cardenolide and pregnaneglycosides. Elimination of 2-deoxysugars by mild acid hydrolysis gave a mixture from which some anhydroderivatives and the following compounds could be isolated: uzarigenin ( l ), ascleposide = 3-O-(6-deoxy-β-D -allopyranosyl)-uzarigenin ( 4 ), coroglaucigenin ( 6 ) and two pregnane derivatives (H and J). Compound H could be identified as 3β,14β-dihydroxy5α, 17α-pregnan-20-one ( 10 ). Compound J is probably a new substance, for which we tentatively assign structure 18 , i.e. 3β8β,14β-trihydroxy-5α,17α-pregnan-20-one. We suspect H and J to be artefacts produced from the corresponding 17b-derivatives during acid hydrolysis. 17-iso-H is probably a precursor in the biosynthesis of uzarigenin. The cardenolides of Trachycalymma fimbriatum are the same as found in Asclepias glaucophylla, a closely related species, while the pregnane derivatives of the latter are distinctly higher hydroxylated.     

Die Struktur der Drevogenine. 2. Mitteilung Struktur von Drevogenin P. Glykoside und Aglykone, 278. Mitteilung

Drevogenin A was converted in several steps (acetylation, hydrogenation, dehydration, hydrogenation, the haloform reaction and energetic alkaline hydrolysis) into 3β, 11α, 12β-trihydroxy-5α-etianic acid, which could be characterised by its crystalline methyl ester ( 15 ) and its tri-O-acetyl methyl ester ( 16 ). The same acid was obtained by partial synthesis starting from hecogenin. Taking into consideration earlier results [1], the structure of drevogenin P is proved to be 3β, 11α, 12β, 14β-tetrahydroxy-20-oxo-Δ⁵-pregnene ( 7 ). Energetic hydrolysis of dihydro-3-O-acetyldrevogenin A gave a mixture of 17αH- and 17βH-desacyl-kondurangogenin A, which were obtained in crystalline form after separation by chromatography. The only difference between the basic structures of the drevogenins and kondurangogenin A is the presence of a double bond in the 5-position in the former.     

Alkaloide aus Cortex Condurango

From the CH₂Cl₂ extract of the bark of Marsdenia cundurango Reichenb. fil. (Cortex Condurango) a mixture of basic compounds could be isolated. Repeated thin layer and column chromatography yealded two alkaloids in pure form. For Kondurangamin A, which would be the mayor alkaloid with a content of 0.0007%, the structure was determined as 3β, 14β,20-trihydroxy-11 α-nicotinoyloxy-12β-acetoxy-5α,14β-pregnane and for Kondurangamin B as 3β,11α,12β,14β-tetrahydroxy-20-nicotinoyloxy-5α,14β-pregnane.     

Constituents of Fruit Bodies of Tramete orientalis

A known sterol, 5α,6α-epoxy-5α-crgosta-8(14),22E-diene-3β,7α-diol ( 1 ), and two new sterols, 5α,6α-epoxy-3β,8β,14α-trihydroxy-5α-ergost-22E-en-7-one ( 2 ), (3α,5α),(8β,11β)-diepidioxy-ergost-22E-en-12-one ( 3 ), were isolated and characterized from dried fruit bodies of Trametes orientalis. Their structures were elucidated according to spectral methods.     

Differential-pulse polarography of trichothecene mycotoxins : Determination of Deoxynivalenol,Nivalenol and Fusarenone-X in Maize

The polarographic behaviour of representative trichothecenes is described. Compounds characterized by an α,β-unsaturated carbonyl group or by a macrocyclic lactonic ring were found to be electroactive in a methanolic Britton—Robinson buffer. Differential pulse polarography provides detection limits of the order of 40 nmol l^?1 with linear ranges extending up to 9 μmol l^?1. The application of differential pulse polarography is described for the determination of nivalenol (3α, 4β, 7α, 15-tetrahydroxy-12,13-epoxytrichotec-9-en-8-one), deoxynivalenol (3α, 7α, 15-trihydroxy-12,13-epoxytrichothec-9-en-8-one) and fusarenone-X (3α, 7α, 15-trihydroxy-4 β-acetoxy-12,13-epoxytrichothec-9-en-8-one) in infected maize. A suitable liquid/liquid extraction and chromatographic cleanup procedure is reported. Detection limits for the overall procedure and for a sample size of 50 g are of the order of 50 ng g^?1 while average recoveries range from 20 to 70% at the 1 μg g^?1 level. Polarographic results are compared with those obtained by a gas-chromatographic method.     

Cardenolides ofCoronilla glauca andC. scorpioides

The cardenolide glycosides glucocorotoxigenin, scorpioside, and coronillobioside and a new compound which has been called glucocoroglaucigenin have been isolated from the seeds ofCoronilla glauca L. for the first time. The new glycoside has the structure of 3β-(β-D-glucopyranosyloxy)-14,19-dihydroxy-5α-card-20(22)-enolide. This glycoside has also been isolated from the seeds ofC. scorpioides.     

Tordanone,un stéroïde replié avec une jonction de cycle A/B β-cis (5β) et B/C α-cis(8α)

Tordanone, a Twice Bent Steroid Structure with Ring A/B β-cis(5β)- and Ring B/C α-cis(8α)-Fused The 3β, 14α, 25-trihydroxy-5β, 8α-cholestan-6-one ( = tordanone; 4 ) has been prepared by stereospecific hydrogenation of 3β, 14α, 25-trihydroxy-5β-cholesta-7,22ξ-dien-6-one ( 5 ). This is the first stereospecific synthesis of a B/C cis-fused steroid belonging to the 5β, 8α -cholestane group with a H-atom at positions 5β (A/B cis-fused) and 8α. The resulting twice bent structure shows a particularly strong steric hindrance of the β-face where CH₃(18) at the C/D ring junction and H_β? C(7) of the B ring are very close to each other. Structural features and mechanistic aspects of the hydrogenation are discussed.     

Microbial transformation of two 15α-hydroxy-ent-kaur-16-ene diterpenes by Mucor plumbeus

The microbiological transformation of candidiol (15α,18-dihydroxy-ent-kaur-16-ene) by Mucor plumbeus led to 3β,15α,18-trihydroxy-ent-kaur-16-ene, 6α,15α,18-trihydroxy-ent-kaur-16-ene, 3α,15α,18-trihydroxy-ent-kaur-16-ene, 11β,15α,18-trihydroxy-ent-kaur-16-ene and 15α,17,18-trihydroxy-11β,16β-epoxy-ent-kaurane, whilst the incubation of 15α,19-dihydroxy-ent-kaur-16-ene gave 9β,15α,19-trihydroxy-ent-kaur-16-ene, 3α,15α,19-trihydroxy-ent-kaur-16-ene, 11β,15α,19-trihydroxy-ent-kaur-16-ene, 6α,15α,19-trihydroxy-ent-kaur-16-ene, 15α,17,19-trihydroxy-11β,16β-epoxy-ent-kaurane, 19-(β-d-glucopyranosyl)-15α-hydroxy-ent-kaur-16-ene and 19-(β-d-glucopyranosyl)-15-oxo-ent-kaur-16-ene. An interesting rearrangement in dilute acid medium of 9β,15α,19-trihydroxy-ent-kaur-16-ene into 16-oxo-19-hydroxy-ent-abiet-8(9),15-diene, is also described in this work.