The glycosides of Marsdenia erecta R. Br. I. Isolation, glycoside and aglycone. 325

Dried leaves of Marsdenia erecta R. Br. gave over 6% of a crude glycoside mixture, the main portion of which consisted of weakly polar material, soluble in ether or chloroform. By mild acid hydrolysis it yielded crude sugars and aglycones. The following four crist. sugars were isolated: D -cymarose, D -oleandrose and two bioses: pachybiose and marsectobiose (C₁₄H₂₄O₈, new). By PC. and TLC. the presence of digitoxose, canarose, thevetose and 3-O-methyl-6-deoxyallose could be demonstrated. The crude acyl-genin mixture contained β-sitosteryl-β-D -glucopyranoside and three highly hydroxylated pregnane derivatives: drevogenin-P, 17 β-marsdenin (C₂₁H₃₂O₆, new) and marsectohexol (C₂₁H₃₄O₆, new), all partly esterified with acetic, tiglic and benzoic acid. Five crist. acyl-genins (A1–A5) were isolated by chromatography, but most of them still were mixtures. After alkaline hydrolysis of the crude acyl-genins 6 acyl-free compounds were obtained. 4 of them were identical with the above mentioned substances, the other two: 17-iso-drevogenin-P and marsdenin (17 α-marsdenin) are formed from drevogenin-P and 17 β-marsdenin by isomerisation.     

Die Glykoside der Wurzeln von Kanahia laniflora (FORSSK.) R. BR. 1. Mitteilung: Isolierungen. Glykoside und Aglykone, 299. Mitteilung

The roots of Kanahia laniflora (FORSSK .) R. BR . contain, in addition to small quantities of cardenolides, a large amount of ester glycosides which are difficulty separable from one another. However, two of these ester glycosides were obtained in a nearly pure form. The crude mixture of ester glycosides, after mild acidic hydrolysis, gave a mixture of acyl-genins and three sugars: D -oleandrose, D -digitoxose and D-canarose, all of which were obtained in crystalline form. Acetic acid, benzoic acid and another unidentified acid were obtained on alkaline hydrolysis of the mixture of acyl-genins along with 17-isolineolon, lineolon, deacetylmetaplexigenin and a small amount of sarcostin-ketone. Besides these known genins, three probably new genins (α, τ, λ) were obtained in small, but crystalline amounts.     

Die Glykoside der Samen von Stapelia gigantea N. E. Br. Glykoside und Aglykone, 275. Mitteilung

The seeds of Stapelia gigantea are very rich in ester glycosides (ca. 5,9%). Mild acid hydrolysis gave a mixture of sugars which, after paper chromatography and electrophoresis, was found to be probably composed of cymarose, oleandrose, digitoxose, arabino-2,6-dideoxyhexose (= canarose) and pachybiose. The mixture of the raw genins gave after alkaline hydrolysis a mixture of about nine deacyl genins (C, D, E, F1, F2, F3, G, H, J); the acids split off during hydrolysis were not identified. The nine deacyl genins are probably closely related pregnane derivatives. The main component (E), C₂₁H₃₀O₄, was obtained in crystalline state, and was named stapelogenin. Its probable structure is reported in the following publication.     

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.     

Viminolon,Strukturbeweis. Glykoside und Aglykone, 315. Mitteilung

Reduction of di-O-benzoyl-viminolon ( 1 ) with LiAlH₄ gave a mixture of 17-isopregn-5-ene-heptols. Treatment of this mixture with NaIO₄ produced the amorphous 12-O-formyl sarcostinketone (= 12-O-formyl-3β, 8β, 12β, 14β-tetrahydroxy androst-5-en-20-one) ( 4 ). This together with former results proves the structure of 1 .     

Stapelogenin,vermutliche Struktur. Glykoside und Aglykone, 276. Mitteilung

Stapelogenin, C₂₁H₃₀O₄, shows a double bond and two hydroxyl groups which can be acetylated. On the grounds of UV.-, IR.-, and NMR-spectra as well as mass spectra, the probable structure is that of a 3β, 12β-dihydroxy-(18, 20β), (14β, 20α)-diepoxy-Δ⁵-pregnene ( 1 ). The exact position of the hydroxyl group, assumed to be 12β, is particularly unsure, as it could also be situated 11α- or 12α-position.     

Alloglaucotoxigenin,Strukturbestimmung Glykoside und Aglykone, 280. Mitteilung

The structure of alloglaucotoxigenin is shown to be that of 3β, 14β, 15β-trihydroxy-19-oxo-5α-carda-20:22-enolide (IV) in the following way: The 19-oxo group could be eliminated by reduction of the corresponding mercaptal. The structure of the resulting 3β, 14β, 15β-trihydroxy-5α-carda-20:22-enolide, obtained in the acetylated form, was established through degradation and through partial synthesis by treatment of Δ¹⁴-anhydro-uzarigenin (XIII) with osmium tetroxide. The isomeric 3β,14α, 15α-trihydroxy-cardenolide was also formed in large quantities. The substance XI showed in its optical rotatory dispersion curve a positive, and substance XIV a negative COTTON effect.     

Herzwirksame Glykoside aus der weissen Meerzwiebel. Konstitution des Scilliphäosids und des Glucoscilliphäosids. 55. Mitteilung über Herzglykoside [1]

Scilliphaeoside (I), C₃₀H₄₂O₉, and glucoscilliphaeoside (III), C₃₆H₅₂O₁₄, represent two minor glycosides which occur in the bulbs of the white sea onion or squill [Scilla (= Urginea) maritima (Baker) L.]. Glucoscilliphaeoside is easily converted into scilliphaeoside and D-glucose by selective enzymatic cleavage with β-glucosidases (e. g. strophanthobiase). Acid hydrolysis splits glucoscilliphaeoside into anhydroscilliphaeosidin (IV) and L-scillabiose (= β-D -glucosyl-L -rhamnose), scilliphaeoside yields the same anhydro-aglycone IV and L-rhamnose. The true genin scilliphaeosidin (VI), C₂₄H₃₂O₅, has now been gained by a combined oxidative and hydrolytic cleavage of the rhamnose residue of scilliphaeoside. By chemical evidence and spectroscopical data scilliphaeosidin is characterized as a trihydroxy-Δ⁴-steroid of the bufadienolide type. The assumed locations of the three hydroxylic functions at C-3, C-12 and C-14 are established by permanganate degradation of the lactone ring of di-O-acetyl-scilliphaeosidin (VII) to the etianic acid derivatives XIII and XIV, which are also available from digoxigenin. These correlations prove the structure of scilliphaeoside (I) as 12β-hydroxy-proscillaridin A, glucoscilliphaeos de (III) representing 12β-hydroxy-scillaren A.     

Die Glykoside der Wurzeln von Xysmalobium dilatatum WEIMARCK. 1. Mitteilung: Isolierungen. Glykoside und Aglykone, 327. Mitteilung

The roots of Xysmalobium dilatatum Weimarck contain uzarin and xysmalorin as major glycosides. The same two compounds are also present as main components in the glycoside mixture from the roots of Xysmalobium undulatum. In addition to that, X. dilatatum also contains appreciable amounts of pregnane derivatives, linked to 2-deoxy-sugars. Four such xanthydrolpositive compounds (the dilatoides A, B, C and D) have been isolated in amorphous but pure or nearly pure form; they have not been detected in the roots of X. undulatum.     

Lokalisierung der Ketogruppe in Inandenin-onen. 160. Mitteilung über Alkaloide

Localization of the keto group in Inandenin-ones . By Schmidt degradation of the spermidine alkaloids inandenine-12-on ( 1 ) and inandenine-13-on ( 2 ) from Oncinotis inandensis followed by hydrolysis, acetylation and esterification four different types of products were obtained: the dicarboxylic diesters 9 and 10 , the ω-amino-carboxylic esters 11 and 12 , the acetylated polyamines 14 and 15 , and the acetylated triaminecarboxylic esters 16 and 17 . By GLC. and mass spectral analysis of these degradation products, and by comparison with synthetic compounds it was possible to confirm the structures 1 and 2 . The same alkaloid mixture ( 1+2 ) was obtained from the leaves of Oncinotis nitida BENTH .     

Die Cardenolide und Pregnan-Glykoside der Wurzeln von Asclepias lilacina WEIMARCK. I. Isolierungen Glykoside und Aglykone, 290. Mitteilung

The dried roots of Asclepias lilacina contain ca. 14% glykosides, in which both cardenolides and ester glycosides of pregnane derivatives are present, the latter predominating. Uzarigenin, coroglaucigenin, and their corresponding glycosides ascleposide and frugoside, resp., were shown to be present; of these four, uzarigenin was isolated in crystalline form. The ester glycosides, some of which could be isolated in a crystalline state, are predominantly composed of the aglycones 20-O-acetyl-12-O-benzoyl-sarcostin and 12,20-di-O-benzoyl-sarcostin, besides which esters of desacetyl-metaplexigenin, lineolon, and dihydrosarcostin are also present. These aglycones are mostly attached to various trisaccharides which are composed of at least two 2-deoxy-sugar residues. Mild acid hydrolysis gave, besides the genins, 7 sugars, namely cymarose, oleandrose, digitoxose, 3-O-methyl-6-deoxy-D-allose (U3), as well as 3 unknown sugars U1, U2 and U5 which are probably disaccharides. U1 and U2 were isolated in crystalline form; they are isomeric and have been named asclepobiose and lilacinobiose; they are probably composed of units similar to those in the isomeric pachybiose.     

Thermische Lactonisierung von Estern γ-Brom-α, β-ungesättigter Carbonsäuren zu Δα-Butenoliden. Direkte γ-Bromierung von α, β-ungesättigten Säuren

By heating with iron powder at 120–150° some γ-bromo-α, β-unsaturated carboxylic methyl esters, and, less smothly, the corresponding acids, were lactonized to Δ^7alpha;-butenolides with elimination of methyl bromide. The following conversions have thus been made: methyl γ-bromocrotonate ( 1c ) and the corresponding acid ( 1d ) to Δ^α-butenolide ( 8a ), methyl γ-bromotiglate ( 3c ) and the corresponding acid ( 3d ) to α-methyl-Δ^α-butenolide ( 8b ), a mixture of methyl trans- and cis-γ-bromosenecioate ( 7c and 7e ) and a mixture of the corresponding acids ( 7d and 7f ) to β-methyl-Δ^α-butenolide ( 8c ). The procedure did not work with methyl trans-γ-bromo-Δ^α-pentenoate ( 5c ) nor with its acid ( 5d ). Most of the γ-bromo-α, β-unsaturated carboxylic esters ( 1c, 7c, 7e and 5c ) are available by direct N-bromosuccinimide bromination of the α, β-unsaturated esters 1a, 7a and 5a ; methyl γ-bromotiglate ( 3c ) is obtained from both methyl tiglate ( 3a ) and methyl angelate ( 4a ), but has to be separated from a structural isomer. The γ-bromo-α, β-unsaturated esters are shown by NMR. to have the indicated configurations which are independent of the configuration of the α, β-unsaturated esters used; the bromination always leads to the more stable configuration, usually the one with the bromine-carrying carbon anti to the carboxylic ester group; an exception is methyl γ-bromo-senecioate, for which the two isomers (cis, 7e , and trans, 7d ) have about the same stability. The N-bromosuccinimide bromination of the α,β-unsaturated carboxylic acids 1b , 3b , 4b , 5b and 7b is shown to give results entirely analogous to those with the corresponding esters. In this way γ-bromocrotonic acid ( 1 d ), γ-bromotiglic acid ( 3 d ), trans- and cis-γ-bromosenecioic acid ( 7d and 7f ) as well as trans-γ-bromo-Δ^α-pentenoic acid ( 5d ) have been prepared. Iron powder seems to catalyze the lactonization by facilitating both the elimination of methyl bromide (or, less smoothly, hydrogen bromide) and the rotation about the double bond. α-Methyl-Δ^α-butenolide ( 8b ) was converted to 1-benzyl-( 9a ), 1-cyclohexyl-( 9b ), and 1-(4′-picoly1)-3-methyl-Δ^α-pyrrolin-2-one ( 9 c ) by heating at 180° with benzylamine, cyclohexylamine, and 4-picolylamine. The butenolide 8b showed cytostatic and even cytocidal activity; in preliminary tests, no carcinogenicity was observed. Both 8b and 9c exhibited little toxicity.     

Die Glykoside der Wurzeln von Xysmalobium dilatatum Weimarck. 2. Mitteilung: Teilstruktur der Dilatoside. Glykoside und Aglykone, 328. Mitteilung

The four dilatosides A, B, C and D (ester glycosides isolated from Xysmalobium dilatatum) differ from each other only in the sugar portion. They all contain the same aglycone: 12-O-acetyl-17-isolineolone (=12-O-acetyl-17-isodeacyl-cynanchogenin) ( 6 ). Its mass spectrum is discussed. In dilatoside A ( 1 ) three molecules of D -oleandrose ( 7 ) are linked to this aglycone, in dilatoside B ( 2 ) one D -canarose ( 8 ) and two oleandrose units, in dilatoside C ( 3 ) two canarose and three oleandrose, and in dilatoside D ( 4 ) probably three canarose and two oleandrose units.     

Photochemische Reaktionen. 104. Mitteilung [1]. Zur Photospaltung der C,C-Oxiranbindung konjugierter γ, δ-Epoxy-enone: Photolyse von 4-Methyliden-5,6-epoxy-5,6-dihydro-β-jonon

The photoinduced cleavage of the C,C-oxirane bond of γ, δ-epoxy-enones: UV.-irradiation of 4-methylidene-5,6-epoxy-5,6-dihydro-β-ionone On ¹n, π*-excitation (λ ≥ 347 nm, pentane) 5 gives the isomeric bicyclic ether 10 in 75% yield (s. Scheme 2). In methanol the photoconversion of 5 to 10 is strongly reduced (12%) in favour of the formation of the methanol adduct 11 (43%). On photolysis in aqueous acetonitrile 5 is converted to the bicyclic ether 10 (9%), the dihydrofurane 12 (18%) as well as to the triketones 13A and 13B (7%), and 14 (23%). On ¹π, π*-excitation (λ = 254 nm) in pentane no 10 is formed, but 5 isomerizes to the tricyclic cyclopropyl compound 16 (59%), the allenic product 17 (10%), and the cyclopropene compound 18 (12%; s. Scheme 3). Photolysis in methanol furnishes 11 (63%), and 18 (4%), but no tricyclic cyclopropyl compound 16 . In a secondary photoreaction (λ = 254 nm) the dihydrofurane 12 is isomerized to the bicyclic cyclopropyl compound 20 . Evidence is given that the products 11 and 13 are formed by solvent addition to an intermediate ketonium ylide b (s. Scheme 12). The presence of b is further proven by the formation of 12 , a product of an electrocyclization of b . On photofragmentation of b carbenoids d and e are presumably formed (s. Scheme 14). 1,2-Hydrogen shift in d yields the allene derivative 17 , and cyclization of d gives the cyclopropene compound 18 . On the other hand, e cyclizes to the non isolated cyclopropene compound 69 which is transformed to 16 by an intramolecular [4 + 2]-cycloaddition. The present investigation shows that the photochemistry of 5 is determined by photoinduced C,C-bond cleavage of the oxirane ring. This is in sharp contrast to the photochemistry of conjugated γ, δ-epoxy-enones without the additional double bond in ε, ζ-position, where selective photocleavage of the C(λ), O-bond is observed.     

Herstellung von 3-Oxo-17β-hydroxy-1,19-cyclo-5α-androstan. Über Steroide, 219. Mitteilung

Under the influence of radical anions generated from lithium and biphenyl, 3-oxo-17β-acetoxy-19-mesyloxy-Δ¹-5α-androstane was converted into 3-oxo-17β-acetoxy-1, 19-cyclo-5α-androstane.     

The structure of Genin G(12-O-benzoyl-desacetylmetaplexigenin) and H (di-O-benzoyl-viminolon) from the stems of Sarcostemma viminale (L.) R. Br

The following structures for the two new genins G and H from Sarcostemma viminale have been deduced. Genin G is shown to be 12-O-benzoyl-deacetylmetaplcxigenin ( 3 ). On the basis of physical data, its behaviour in KOH-methanol solution and its positive test with alcaline silver-diammine solution, the structure of 3β, 8β, 14β, 17β-tetrahydroxy-12β, 21-dibenzoyloxy-20-oxo-17α-pregn-5-ene ( 4 ) is proposed for genin H. This substance therefore contains a dihydroxyacetone group like some corticoids (e.g. Cortisol), but with different stereochemistry at C-14 and C-17.     

Intramolecular energy transfer between chromophores separated by a rigid steroid bridge: II. Energy transfer as a probe to determine the ratio of two epimers

The singlet-singlet intramolecular energy transfer between naphthalene moiety and dansy! group held apart by a rigid steroid bridge was investigated for two molecules: β-(1-naphthyl) acetoxy-17α-dansyl-Δ⁵androstene (3a) and 3β-(1-naphthyl)acetoxy-17 β-dansyl-Δ⁵androstene (3b). The rates of energy transfer for 3a and 3b in cyclohexane are 6.9 × 10⁶ and 1.1 × 10⁸ s^?1 respectively. The difference in energy transfer rate between 3a and 3b is attributed to the different donor-acceptor separation and orientation. The ratio of the two epimers in the synthesized product mixture was obtained from the fluorescence decay measurements.     

Photochemische Cycloadditionen von 3-Phenyl-2H-azirinen mit Benzoyl-, Äthoxycarbonyl- und Vinylphosphonaten 34. Mitteilung über Photoreaktionen

The irradiation of the 3-phenyl-2H-azirines 1a–c in the presence of diethyl benzoylphosphonate ( 8 ) in cyclonexane solution, using a mercury high pressure lamp (pyrex filter), yields the diethyl (4, 5-diphenyl-3-oxazolin-5-yl)-phosphonates 9a–c (Scheme 3). In the case of 1b a mixture of two diastereomeric 3-oxazolines, resulting from a regiospecific but non-stereospecific cycloaddition of the benzonitrile-benzylide dipole 2b to the carbonyl group of the phosphonate 8 , was isolated. Benzonitrile-isopropylide ( 2a ), generated from 2,2-dimethyl-3-phenyl-2H-azirine ( 1a ), undergoes a cycloaddition reaction to the ester-carbonyl group of diethyl ethoxycarbonylphosphonate ( 15 ) with the same regiospecificity to give the 3-oxazoline derivative 16 (Scheme 5). The azirines 1a–c , on irradiation in benzene in the presence of diethyl vinylphosphonate ( 17 ) give non-regiospecifically the Δ¹-pyrrolines 13a–c and 14a–c (Scheme 6).     

Steroids and sex hormones. 242. Preparation of 14-beta-hydroxy-2-keto-delta-16-steroids: a new highly productive access to 33-O-methyl-17-alpha, 20-xi-tetrahydrobatrachotoxinin A

A novel method for the reductive epoxide opening in a 14β, 15β-epoxy-20-oxo-Δ¹⁶-pregnene 4 affords an almost quantitative yield of the 14β-hydroxy-20-oxo-Δ¹⁶-pregnene 5. This leads to a considerable improvement of the formerly published synthesis of 3-O-methyl 17 α, 20ξ-tetrahydrobatrachotoxinin A ( 2 ) [3].     

Photoinduzierte 1, 3-dipolare Cycloaddition von 3-Phenyl-2H-azirinen an Azodicarbonsäure-diäthylester. 32. Mitteilung über Photoreaktionen

Irradiation of 2, 2-dimethyl-3-phenyl- ( 1a ), 2, 3-diphenyl-2H-azirine ( 1b ) or the azirine-precursors 1-azido-1-phenyl-propene ( 2a ) and 1-azido-1-phenyl-ethylene ( 2b ), respectively, in benzene in the presence of azodicarboxylic acid diethylester, yields the corresponding 1, 2-carbethoxy-3-phenyl-Δ³-1, 2, 4-triazolines 4a–d (Scheme 1). Refluxing 4 ( a, c or d ) in 0, 2–0, 4M aqueous ethanolic potassium hydroxide leads to the formation of the 1-carbethoxy-3-phenyl-Δ²-1, 2, 4-triazolines 6 ( a, c or d ). Under the same conditions 4b is converted to 3, 5-diphenyl-1, 2, 4-triazole ( 7b , Scheme 2). In 10M aqueous potassium hydroxide solution heating of either 4 ( c or d ) or 6 ( c or d ) yields the 3-phenyl-1, 2, 4-triazoles 7 ( c or d ). Photolysis of 1-carbethoxy-5, 5-dimethyl-3-phenyl-Δ²-1, 2, 4-triazoline ( 6a ) in benzene in the presence of oxygen and trifluoroacetic acid methylester gives the 5-methoxy-2, 2-dimethyl-4-phenyl-5-trifluoromethyl-3-oxazoline ( 13 , Scheme 5). 5, 5-Dimethyl-3-phenyl-1, 2, 4-triazole seems to be the intermediate, which on losing nitrogen gives the benzonitrile-isopropylide ( 3a ).