Steroids and sex hormones, 231. The synthesis of N-acetyl-3-aza-A-homo-5-beta, 10-alpha-andostran and its 5-alpha-isomers

A synthesis of N-acetyl-3-aza-A-homo-5β, 10α-androstane ( 14 ) and N-acetyl-3-aza-A-homo-5α, 10α-androstane ( 15 ) is described, starting from 2-oxo-17β-acetoxy-Δ⁵-10α-androstane ( 4 ).     

Steroids and sex hormones. The synthesis of 1-beta, 4-beta-oxido-3-aza-17-beta-hydroxy-A-homo-5-alpha-androstane

A sterically controlled transformation of 3-oxo-17β-acetoxy-Δ^1?-α-androstene ( 2 ) into 1β,4β-oxido-3-aza-17β-hydroxy-A-homo-5α-androstane ( 16 ) is described. With the exception of two conversions [ 14 → 15 (60%); 15 → 16 (50%)], the yields of the remaining seven steps are higher than 75% each. The reaction sequence will serve as a model for an analogous partial synthesis of samandarine ( 1 ).     

Carbon-13 NMR spectra of some pentacyclic triterpenoids with the olean-12-ene and 18α-olean-12-ene skeleton

The ¹³C NMR spectra of some pentacyclic triterpenoids, 3β-acetoxy-11-oxo-olean-12-ene-30-oic acid methyl ester, 3β-acetoxy-11-oxo-olean-12-ene-29-oic acid methyl ester, the corresponding 11-desoxo methyl esters, 3β-acetoxy-11-oxo-18α-olean-12-en-30-oic acid methyl ester and 3β-acetoxy-11-oxo-18α-olean-12-en-29-oic acid methyl ester are discussed. The shielding data are interpreted in term of the different orientation of the carbomethoxy group and of the change in configuration at the D/E ring junction and are diagnostically valuable for the differentiation of the mentioned compounds.     

Photochemical Rearrangement of a Steroidal α,β-Epoxylactone. Photochemical reactions,XI [1]

The UV. irradiation of 17β-acetoxy-4α, 5α-epoxy-2-oxaandrostan-3-one ( 7 ) yields 17β-acetoxy-2-oxa-10(5 → 4)abeo-4ζ (H)-androsta-3,5-dione ( 11 ). A non-photochemical synthesis of 11 , proceeding in lower yield, is also described.     

20, 21-Azirdin-Steroide: Reaktion von Derivaten der Oxime von 5-Pregnen-20-on,9β,10α-5-Pregnen-20-on und 9β,10α-5,7-Pregnadien-20-on mit Lithiumaluminiumhydrid und von 3β-Hydroxy-5-pregnen-20-on-oxim mit Grignard-Verbindungen

20, 21-Aziridine Steroids: Reaction of Derivatives of the Oximes of 5-Pregnen-20-one, 9β, 10α-5-Pregnen-20-one and 9β, 10α-5,7-Pregnadiene-20-one with Lithium Aluminium Hydride, and of 3β-Hydroxy-5-pregnen-20-one Oxime with Grignard Reagents. Reduction of 3β-hydroxy-5-pregnen-20-one oxime ( 2 ) with LiAlH₄ in tetrahydrofuran yielded 20α-amino-5-pregnen-3β-ol ( 1 ), 20β-amino-5-pregnen-3β-ol ( 3 ), 20β, 21-imino-5-pregnen-3β-ol ( 6 ) and 20β, 21-imino-5-pregnen-3β-ol ( 9 ). The aziridines 6 and 9 were separated via the acetyl derivatives 7 and 10 . The reaction of 6 and 9 with CS₂ gave 5-(3β-hydroxy-5-androsten-17β-yl)-thiazolidine-2-thione ( 8 ). Treatment of the 20-oximes 12 and 15 of the corresponding 9β,10α(retro)-pregnane derivatives with LiAlH₄ gave the aziridines 13 and 16 , respectively. Their deamination led to the diene 14 and triene 17 , respectively. Reduction of isobutyl methyl ketone-oxime with LiAlH₄ in tetrahydrofuran yielded 2-amino-4-methyl-pentane ( 19 ) as main product, 1, 2-imino-4-methyl-pentane ( 22 ) as second product and the epimeric 2,3-imino-4-methyl-pentanes 20 and 21 as minor products. – 3β-Hydroxy-5-pregnen-20-one oxime ( 2 ) was transformed by methylmagnesium iodide in toluene to 20α, 21-imino-20-methyl-5-pregnen-3β-ol ( 23 ) and 20β, 21-imino-20-methyl-5-pregnen-3β-ol ( 26 ). Acetylation of these aziridines was accompanied by elimination reactions leading to 3β-acetoxy-20-methylidene-21-N-acetylamino-5-pregnene ( 30 ) and 3β-acetoxy-20-methyl-21-N-acetylamino-5,17-pregnadiene ( 32 ). The reaction of oxime 2 with ethylmagnesium bromide in toluene gave 20α, 21-imino-20-ethyl-5-pregnen-3β-ol ( 24 ) and 20α,21-imino-20-ethyl-5-pregnen-3β-ol ( 27 ). Acetylation of 24 and 27 led to 3β-acetoxy-20-ethylidene-21-N-acetylamino-5-pregnene ( 31 ), 3β-acetoxy-20-ethyl-21-N-acetylamino-5,17-pregnadiene 33 and 3β, 20-diacetoxy-20-ethyl-21-N-acetylamino-5-pregnene ( 37 ). With phenylmagnesium bromide in toluene the oxime 2 was transformed to 20β, 21-imino-20-phenyl-5-pregnen-3β-ol ( 25 ) and 20β,21-imino-20-phenyl-5-pregnen-3β-ol ( 28 ). Acetylation of 25 and 28 yielded 3β-acetoxy-20-phenyl-21-N-acetylamino-5, 17-pregnadiene ( 34 ) and 3β,20-diacetoxy-20-phenyl-21-N-acetylamino-5-pregnene ( 39 ). LiAlH₄-reduction of 39 gave 3β, 20-dihydroxy-20-phenyl-21-N-ethylamino-5-pregnene ( 41 ). – The 20, 21-aziridines are stable to LiAlH₄. Consequently they are no intermediates in the formation of the 20-amino derivatives obtained from the oxime 2 .     

The Crystal and Molecular Structure of 3-Oxo-17β-acetoxy-Δ4-14α-methyl-8α, 9β, 10α, 13α-estrene

The crystal and molecular structure of 3-oxo-17β-acetoxy-Δ⁴-14α-methyl-8α, 9β, 10α, 13α-estrene, C₂₁H₃₀O₃, has been determined by X-ray diffraction analysis. The crystals belong to the orthorhombic space group P2₁2₁2₁, with the cell dimensions a = 12.093 Å, b = 19.667 Å, c = 7.746 Å; Z = 4. Intensity data were collected at room temperature with an automatic four-circle diffractometer. The structure was solved by direct methods and the parameters were refined by least-squares analysis. All the hydrogen atoms were included in the refinement. The final R value was 0.038 for 1413 observed reflections. The conformation of ring A is intermediate between a half-chair and a 1, 2-diplanar form. The hydrogens at C(9) and C(10) are anti, the B/C ring junction is trans, and rings B and C adopt chair conformations. Ring D is cis fused and is halfway between C₂ and C_s forms.     

Mass spectra of 17ξ-hydroxy-5ξ-androstane C(3) ketone and C(3ξ) alcohol isomers

Positive ion electron impact mass spectral data for the four isomeric 17ξ-hydroxy-17ξ-methyl-5ξ-androstane C(3) ketones and the eight isomeric C(3ξ) alcohols are reported. In contrast to earlier reports, no general correlation was observed between the [M? H₂O]⁺˙/[M]⁺˙ ratio and the configuration at C(17). The ratios of the intensity of several fragment ions to that of the molecular ion do differentiate between the 5α- and 5β-isomers in both C(3) ketones and alcohols, the extent of fragmentation being greater for 5β-steroids. All of these fragments probably involve elimination of a water molecule at some stage in their formation. Elimination of water is also enhanced for 3α- v. 3β-hydroxysteroids, particularly in a 5β-isomer.     

Dissimilar behaviour of 3β, 16α-dihydroxy-5α-androstan-17-one Diacetate under Basic and Acidic Conditions

The base-catalysed rearrangement of 3β, 16α-dihydroxy-5α-androstan-17-one diacetate ( 1 ) in (D₆)benzene/ CD₃OD to 3β, 17β-dihydroxy-5α-androstan-16-one ( 3 ) is followed by ¹³C-NMR spectroscopy. By the same procedure, it is determined that in (D₆)benzene/CD₃OD, but under acid catalysis, 1 does not rearrange to 3 but yields the intermediate product 3β, 16α-dihydroxy-5α -androstan-17-one 17α -methyl hemiacetal ( 5 ).     

Photochemische Reaktionen. 76.Mitteilung [1]. UV.-Bestrahlung von 11-Oxo-Steroiden V Die Photoisomerisierung von 3,20-Diäthylendioxy-5α,14β,17α-pregnan

The UV.-isomerisation of 11-oxo-14β,17α-pregnane 9 to the 11,19-cyclo-derivative 11 is described. In addition the Pb(OAc)₄-fragmentation of photoproduct 11 was investigated. 11 yielded besides the expected 11-oxo-19-hydroxy-pregnane 18 the novel 9,11-seco-11,19-cyclosteroid 19 . The structure of 19 was established by chemical transformations and subsequently confirmed by X-ray analysis [2].     

Conformations of the Ten-membered Ring in 5, 10-Secosteroids. III: (Z)-3β- and (Z)-3α-Hydroxy-5, 10-seco-1 (10)-cholesten-5-one Esters and (Z)-5, 10-seco-1 (10)-Cholestene-3, 5-dione

(Z)-3β-Acetoxy- and (Z)-3 α-acetoxy-5, 10-seco-1 (10)-cholesten-5-one ( 6a ) and ( 7a ) were synthesized by fragmentation of 3β-acetoxy-5α-cholestan-5-ol ( 1 ) and 3α-acetoxy-5β-cholestan-5-ol ( 2 ), respectively, using in both cases the hypoiodite reaction (the lead tetraacetate/iodine version). The 3β-acetate 6a was further transformed, via the 3β-alcohol 6d to the corresponding (Z)-3β-p-bromobenzoate ester 6b and to (Z)-5, 10-seco-1 (10)-cholestene-3, 5-dione ( 8 ) (also obtainable from the 3α-acetate 7a ). The ¹H-and ¹³C-NMR. spectra showed that the (Z)-unsaturated 10-membered ring in all three compounds ( 6a , 7a and 8 ) exists in toluene, in only one conformation of type C ₁, the same as that of the (Z)-3β-p-bromobenzoate 6b in the solid state found by X-ray analysis. The unfavourable relative spatial factors (interdistance and mutual orientation) of the active centres in conformations of type C ₁ are responsible for the absence of intramolecular cyclizations in the (Z)-ketoesters 6 and 7 ( a and c ).     

Synthese von Astaxanthin aus β-Jonon. I. Erschliessung der enantiomeren C15-Wittigsalze durch chemische und mikrobiologische Racematspaltung von (±)-3-Acetoxy-4-oxo-β-jonon

Synthesis of Astaxanthin from β-Ionone. I. A Route to the Enantiomeric C₁₅-Wittig Salts by Chemical and Microbial Resolution of (±)-3-Acetoxy-4-oxo-β-ionone Racemic 3-acetoxy-4-oxo-β-ionone ( 10 ) was synthesized from the industrially accessible intermediate β-ionone ( 5 ). Resolution of 10 into its enantiomers was achieved via the corresponding diastereomeric camphanates and by microbial resolution. Site-selective alkylation of racemic and of optically pure 3-acyloxy-4-oxo-β-ionones with vinyl magnesium chloride at ?70° furnished the corresponding 3-acyloxy-4-oxo-9-vinyl-β-ionols which could be transformed to the Wittig salts 1, 3 and 4 , respectively, following known procedures [1].     

Steroids and sexual hormones. Synthetic experiments in the limonin series lV. A new Westphalen-Lettré rearrangement in the 4,4-dimethyl-steroid series]

Applying the HgCl₂/ClCH₂SCH₃-reaction 1. to 4,4-dimethyl-Δ⁵-7-oxo-19-hydroxy-androstene (9) one observes an intramolecular rearrangement of the «Westphalen-Lettré»-type (→11). A related rearrangement is observed by treating 3-oxo-4,4-dimethyl-17β-acetoxy-Δ⁵-androstene (12) with HgCl₂/ClCH₂SCH₃-reagent (→13). Reaction of 3β, 17β-diacetoxy-4,4-dimethyl-19-(methoxymethyl)-Δ⁵-androstene (7) with hydrogenfluoride/urea-reagent gives rise to a similar rearranged product (→15).     

Umwandlung von Cardenoliden durch Mikroorganismen VI. 7β, 11α-Dihydroxydigitoxigenin und Abbau von 7β-Hydroxy-digitoxigenin zum 3β, 7β-Diacetoxy-14-hydroxy-5β, 14β, 17αH-ätiansäure-methylester. Mitteilung über Reaktionen mit Mikroorganismen [1]

Digitoxigenin ( 3 ) was transformed by a Fusarium spec. to 7β-hydroxydigitoxigenin ( 1 ) 1β, 7β-dihydroxydigitoxigenin ( 4 ) and to the hitherto unknown 7β, 11α-dihydroxydigitoxigenin ( 9 ). 7β-acetoxy-digitoxigenin ( 2 ) was degraded to methyl 3β, 7β-diacetoxy-14-hydroxy-5β, 14β, 17αH-etianate ( 11 ).     

The synthesis of β-heteroarylamino-α,β-dehydro-α-amino acid and β-heteroarylamino-α-amino acid derivatives

From heteroarylaminomethyleneoxazolones 4 , obtained from N-heteroarylformamidines 2 and 2-phenyl-5-oxo-4,5-dihydro-1,3-oxazole ( 3 ), the following β-heteroarylamino-α,β-dehydro-α-amino acid derivatives were prepared: methyl 8 and ethyl esters 9 , amides 10 and 11 , hydrazides 12 , and azides 15 . By catalytic hydrogenation the compounds 4 were converted into β-heteroarylamino substituted amides 18 and β-heteroarylamino-α-amino acids 20 .     

Reaction of a 5α-bromo-6β,19-epoxysteroid with BF3·Et2O/Ac2O: An evidence of a cyclic bromonium cation

Treatment of 3β-acetoxy-5-bromo-6β,19-epoxy-5α-androstan-17-one with Ac₂O and BF₃·OEt₂, produced the cleavage of the epoxy moiety and migration of the bromine atom to afford 3β,19-diacetoxy-6α-bromo-5-hydroxy-5β-androst-17-one in high yield.     

5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成

以5-雄烯二醇为原料,用微生物转化的方法合成了两个重要的神经甾体5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇。所用菌种总枝毛霉为我们自己筛选,并首次应用于5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成中。     

Substituent increments for the 1H-NMR. Chemical shifts of the 18- and 19-methyl protons of steroids. Part II: 9alpha, 10beta(normal)-steroids

In Part II of this series we report 292 substituent increments for the ¹H-NMR. chemical shifts (solvent: CDCl₃) of the 18- and 19-methyl protons of 9α,10β(normal)-steroids relative to 5α,9α,10β,-androstane. The increments were calculated by a least-squares procedure from 988 spectra of 681 different steroids.     

Substituent increments for the 1H-NMR. Chemical shifts of the 18- and 19-methyl protons of steroids. Part I: 9beta, 10alpha(retro)-steroids

This paper reports 261 substituent increments for the ¹H? NMR. chemical shifts (solvent: CDCl₃) of the 18- and 19-methyl protons of 9β, 10α(retro)-steroids relative to 5β,9β,10α,-androstane. The increments were calculated by a least-squares procedure from 1334 spectra of 759 different steroids.     

The synthesis of β-heteroarylamino-α,β-dehydro-α-amino acid derivatives via thiazolones

2-Alkoxy-4-heteroarylaminomethylene-5(4H)-thiazolones 4 were converted with various nucleophiles into β-heteroarylamino-α,β-dehydro-α-amino acid derivatives 11, 14, 15, 16, 17, 18 , and 19 . Reduction of 4 with sodium borohydride in ethanol saturated with gaseous ammonia afforded the corresponding β-heteroaryl-amino substituted alanyl amides 20 . Thiazoledione derivative 7a was transformed with sodium methoxide in methanol into 1-(4,6-dimethylpyrimidinyl-2)-4-mercaptocarbonylimidazol-2(3H)-one ( 8a ).     

Steroids and sex hormones. Quassinoid bitter principles. I. 1-oxo-2-methoxy-4 alpha-methyl-17 beta-hydroxy-delta2-5 alpha-androstene as a model for the ring a structure of quassine]

Starting from 3-oxo-17β-hydroxy-Δ¹-5α-androstene (2b) the preparation of 1-oxo-2-methoxy-4α-methyl-17β-hydroxy-Δ²-5α-androstene (9), a compound with the ring A structure of quassine (1) is described. The key problem of the reaction sequence is shown to be the monomethylation at C(4).