Ergosta-5,7,9(11), 22-tetraen-3β-ol and its 24ξ-Ethyl Homolog,Two New Marine Sterols from the Red Sea Sponge Biemna fortis

The steroidal components of a Red Sea sponge, Biemna fortis, were fractionated through reversed phase HPLC. and analyzed by a combination of physical methods, including high resolution GC./MS. and 360 MHz ¹H-NMR. The sponge contains five conventional Δ⁵-sterols, 1a – c , 1e , 1g , which comprise about 25% of the mixture and 2,5% of gorgosterol (1h) , a sterol never found before in Porifera. Three Δ^5,7,22-sterols were also present as major components in the mixture (～70%): cholesta-5,7,22-trien-3β-ol (2a) , ergosta-5,7,22-trien-3β-ol (2c) and (24R)-ethylcholesta-5,7,22-trien-3β-ol (2e) whereas two new tetra-unsaturated sterols were identified in minor amounts (2%): ergosta-5,7,9(11),22-tetraen-3β-ol (3c) and 24ξ-ethylcholesta-5,7,9 (11), 22-tetraen-3β-ol ( 3e or 3f ). NMR. spectroscopy made possible the assignment of a 24R configuration for all the C(24) substituted sterols isolated in sufficient amount from the mixture. The possible symbiotic, dietary or biosynthetic origins of these sterols are discussed.     

Photosensitized Oxygenation of Abieta-7,9(11)-dien-13β-ol

Dehydration of abiet-8-ene-7β, 13β-diol (ibozol, 1 ) leads to abieta-7,9(11)-dien-13β-ol ( 2 ) which aromatizes slowly to the known abieta-8,11,13-triene ( 3 ). Photosensitized oxygenation of the heteroannular diene 2 yields a mixture from which three compounds were identified; abiet-7-ene-9α, 11α, 13β-triol ( 4 ), abieta-8,11,13-trien-7-one ( 5 ), and abieta-8,11,13-trien-7α-ol ( 6 ).     

Sterol sulfates from the Far Eastern holothurianCucumaria japonica

A chloroform-methanol extract of the musculocutaneous sac of the Far-Eastern holothurianC. japonica has yielded a fraction of sterol sulfates (13% of the weight of the extract, 0.8% of the weight of the dry biomass), the main components of which were derivatives of cholest-5-en-3β-ol, 24-methylene-, 24-ethyl-, and 24-ethylidenecholest-5-en-3β-ols, 5α-cholestan-3β-ol, and 24-methyl- and 24-methylene-5α-cholesten-3β-ol; among the minor components were found the sulfates of 24-ethyl-5α-cholestan-3β-ol of cholesta-5,22-dien-3β-ol, of a Δ⁵-C₃₀ sterol, and also of dienic and trienic C₂₆ sterols.     

Synthesis of (E)-8-aza-11-deoxy-15α- and 15β-hydroxyprost-13-en-1-ol

The synthesis of a prostaglandin E₁ analog, (E)-8-aza-11-deoxy-15α- and 15β-hydroxyprost-13-en-1-ol, is reported.     

The Course of the Catalytic Hydrogenation/Isomerization Reaction of Steroidal Ring B Olefins in the 13β- and 13α-Series

The course of the catalytic hydrogenation and isomerization (H₂/Raney-Ni/dioxane or H₂/Pd/C/EtOH) of Δ^5.7-, Δ⁷-, Δ⁸-, and Δ⁸⁽¹⁴⁾-steroid olefins was shown to depend strongly on the configuration at C(13). The known hydrogenation/isomerization of reactions of Δ^5.7-dienes in the 13β-series to Δ⁷-(H₂/Raney-Ni/dioxane) and Δ⁸⁽¹⁴⁾-olefins (H₂/Pd/C/EtOH) were also confirmed in the 3β, 19-epoxy-13β- and 3-Oxo-19-acetoxy-13β-steroid series (e.g. 32 → 35 → 37 , Scheme 3). On the other hand, in the corresponding 13α-steroid series the same reactions afforded the Δ⁷-. and the Δ⁸-olefins (mixture of products with H₂/Raney-Ni/dioxane; quantitatively the Δ⁸-compounds with H₂/Pd/C/EtOH; s. e.g. Scheme 3). A similar dependence on the C(13) configuration was observed in the allylic oxidation of these olefins with SeO₂ (Fieser's test, see Table), and in the acid catalyzed opening of the 7α, 8α-epoxides (e.g. 60 → 62 + 63 in the 13β-series, and 56 → 64 + 65 in the 13α-series, Scheme 8).     

Synthesis and transformations of (±)-trans-4aβ(H), saα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one

Hydrogenation of 4,7-dimethylcoumarin ( 1 ) in alkaline medium has been shown to furnish a mixture of (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7β-dimethyl-2H-1-benzopyran-2-one ( 2 ), (±)-trans-4aβ(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 3 ) and (±)-cis-4aα(H),8aα(H)-octahydro-4α,7α-dimethyl-2H-1-benzopyran-2-one ( 4 ) in 40:25:35:ratio, respectively. The stereochemistry of the major hydrogenation product 2 , has been established by transforming it to p-menthane derivatives e.g. (±)-2 (R)-[2′(R)hydroxy-4′(R) methylcyclohex-(1′S)-yl]propan-1-ol ( 20 ) and (±)-trans-3α,6β-dimethyl-3aβ(H),7aα(H)-octahydrobenzofuran ( 12 ). Starting from a mixture of lactones 2, 3 and 4 , lactone 3 has been obtained in pure state employing a sequence of reactions.     

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.     

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.     

Minor and Trace Sterols in Marine Invertebrates. XII. Occurrence of 24 (R + S)-isopropenylcholesterol, 24 (R + S)-methylcholesta-5, 25-dien-3β-ol,and 24 (R + S)-methylcholesta-7, 25-dien-3β-ol in the caribbean sponge,Verongia cauliformis

In addition to the two new sterols verongulasterol 11 and 25-dehydroaplysterol 13 of Verongia cauliformis³), which were reported earlier [2] [3], the minor and trace sterols of this sponge include five new sterols listed in the title (with the exception of the known 24 S-methyl-cholesta-5, 25-dien-3β-ol (codisterol, 1b ). The isolation of the 24(R)-epimer of codisterol is of interest, as this compound is a possibly biosynthetic precursor for aplysterol 12 , 25-dehydroaplysterol 13 , and verongulasterol 11 (all 24R) which occur in the same sponge [2]. A partial synthesis from fucosterol ( 4 ) of 24 (R + S)-isopropenylcholesterol ( 9 ), and of 24-isopropylcholesterol ( 10 ) is described.     

Isolierung von 10′-Apo-β-carotin-10′-ol und (3R)-10′-Apo-β-carotin-3,10′-diol (Galloxanthin) aus Rosenblüten. 5. Mitteilung über Rosenfarbstoffe

Isolation of 10′-Apo-β-carotene-10′-ol and (3R)-10′-Apo-β-carotene-3,10′-diol (Galloxanthin) from Rose Flowers The novel (all-E)-10′-apol-β-carotene-10′-ol ( 2 ) and (all-E,3R)-10′-apo-β-carotene-3,10′-diol ( 5 ) have been isolated from petals of one yellow species and various whitish or yellow blend varieties of rose cultivars. Each (all-E)-compound is accompanied by a (Z)-isomer, probably the (9Z)-isomer. Diol 5 proved to be identical with galloxanthin, an apo-10′-carotenol previously isolated from the retina of chicken.     

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 ).     

New Open‐Chain and Cyclic Tetrapeptides,Consisting of α‐, β2‐, and β3‐Amino‐Acid Residues,as Somatostatin Mimics – A Survey

Cyclo‐β‐tetrapeptides are known to adopt a conformation with an intramolecular transannular hydrogen bond in solution. Analysis of this structure reveals that incorporation of a β²‐amino‐acid residue should lead to mimics of ‘α‐peptidic β‐turns’ (cf. A, B, C ). It is also known that short‐chain mixed β/α‐peptides with appropriate side chains can be used to mimic interactions between α‐peptidic hairpin turns and G protein‐coupled receptors. Based on these facts, we have now prepared a number of cyclic and open‐chain tetrapeptides, 7 – 20 , consisting of α‐, β²‐, and β³‐amino‐acid residues, which bear the side chains of Trp and Lys, and possess backbone configurations such that they should be capable of mimicking somatostatin in its affinity for the human SRIF receptors (hsst_1–5). All peptides were prepared by solid‐phase coupling by the Fmoc strategy. For the cyclic peptides, the three‐dimensional orthogonal methodology (Scheme 3) was employed with best success. The new compounds were characterized by high‐resolution mass spectrometry, NMR and CD spectroscopy, and, in five cases, by a full NMR‐solution‐structure determination (in MeOH or H₂O; Fig. 4). The affinities of the new compounds for the receptors hsst_1–5 were determined by competition with [¹²⁵I]LTT‐SRIF₂₈ or [¹²⁵I] [Tyr¹⁰]‐CST₁₄. In Table 1, the data are listed, together with corresponding values of all β‐ and γ‐peptidic somatostatin/Sandostatin^® mimics measured previously by our groups. Submicromolar affinities have been achieved for most of the human SRIF receptors hsst_1–5. Especially high, specific binding affinities for receptor hsst₄ (which is highly expressed in lung and brain tissue, although still of unknown function!) was observed with some of the β‐peptidic mimics. In view of the fact that numerous peptide‐activated G protein‐coupled receptors (GPCRs) recognize ligands with turn structure (Table 2), the results reported herein are relevant far beyond the realm of somatostatin: many other peptide GPCRs should be ‘reached’ with β‐ and γ‐peptidic mimics as well, and these compounds are proteolytically and metabolically stable, and do not need to be cell‐penetrating for this purpose (Fig. 5).     

The Effect of Fluoro Substitution upon the β‐Hairpin Fold of a β‐Tetrapeptide in Methanol

The importance of β‐peptides lies in their ability to mimic the conformational behavior of α‐peptides, even with a much shorter chain length, and in their resistance to proteases. To investigate the effect of substitution of β‐peptides on their dominant fold, we have carried out a molecular‐dynamics (MD) simulation study of two tetrapeptides, Ac‐(2R,3S)‐β^2,3hVal(αMe)‐(2S)‐β²hPhe‐(R)‐β³hLys‐(2R,3S)‐β^2,3‐Ala(αMe)‐NH₂, differing in the substitution at the C_α of Phe2 (pepF with F, and pepH with H). Three simulations, unrestrained (UNRES), using ³J‐coupling biasing with local elevation in combination with either instantaneous (INS) or time‐averaging (AVE) NOE distance restraining, were carried out for each peptide. In the unrestrained simulations, we find three (pepF) and two (pepH) NOE distance bound violations of maximally 0.22 nm that involve the terminal residues. The restrained simulations match both the NOE distance bounds and ³J‐values derived from experiment. The fluorinated peptide shows a slightly larger conformational variability than the non‐fluorinated one.     

Synthesis and polymerization of racemic and optically active substituted β-propiolactones. VI. α-Phenyl β-propiolactone

The synthesis and optical resolution of α-phenyl β-amino-ethylpropionate led to the preparation of optically active α-phenyl β-propiolactones (PhPL) of different optical purities. The enantiomeric excess of PhPL was determined using 200 MHz ¹H-NMR spectroscopy, after complexation with tris[3-(trifluoromethyl hydroxymethylene)-d-camphorato]europium III. It was then polymerized, in bulk and in solution, using a potassium acetate/crown ether complex as initiator. The optically active poly(PhPL)s thus obtained are insoluble in most organic solvents, whereas atactic poly(PhPL)s are soluble in CCl₄, CHCl₃, and dichloroethane. Several differences are observed between the physical properties of optically active and atactic poly(PhPL)s. However, atactic poly(PhPL)s are semi-crystalline polymers, similar to poly(α-disubstituted β-propiolactone)s, but in contrast with poly(α-methyl β-propiolactone). Melting (T_f) and glass transition temperatures, as well as enthalpy of fusion (ΔH), vary with the optical purity of the polymers. For example, atactic poly(PhPL) exhibits a T_f = 94°C and ΔH = 9 J/g as compared to T_f = 119°C and ΔH = 37 J/g for a poly(PhPL) having an enatiomeric excess of 50%.     

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 .     

Preparation of Protected β2‐ and β3‐Homocysteine, β2‐ and β3‐Homohistidine,and β2‐Homoserine for Solid‐Phase Syntheses

The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of β‐peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two β³‐homoamino acid derivatives were obtained by Arndt–Eistert methodology from Boc‐His(Ts)‐OH and Fmoc‐Cys(PMB)‐OH (Schemes 2–4), with the side‐chain functional groups' reactivities requiring special precautions. The β²‐homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti‐enolates to formaldehyde (generated in situ from trioxane) and subsequent functional‐group manipulations. These include OH→O^tBu etherification (for β²hSer; Schemes 5 and 6), OH→STrt replacement (for β²hCys; Scheme 7), and CH₂OH→CH₂N₃→CH₂NH₂ transformations (for β²hHis; Schemes 9–11). Including protection/deprotection/re‐protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (t_R), melting points, optical rotations, HPLC on chiral columns, IR, ¹H‐ and ¹³C‐NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X‐ray crystal‐structure analysis.     

α,α,α′,α′-Tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs) for Resolutions of Alcohols and as Chiral Solvating Agents in NMR Spectroscopy

The use of α,α,α′,α′ -tetraaryl-1,3-dioxolane-4,5-dimethanols ( = TADDOLs;1) as chiral NMR shift reagents (¹H, ¹³C, ¹⁹F) is described. In many cases, the ratio of enantiomeric alcohols and amines can be determined under standard conditions of measurement (CDCl₃ as solvent, room temperature). The preparation and use of a new type of TADDOL, the tetrakis(dimethylamino) derivative 1d , is described. Menthol, octan-2-ol, and oct-1-yn-3-ol are partially resolved by crystallization of clathrates with 1c and 1d .     

Demetallation of α, β, γ, δ-tetra(p-sulfophenyl)porphineiron(III) in sulfuric acid-ethanol-water media

The rate of demetallation of α, β, γ,δ-tetra(p-sulfophenyl)porphineiron (III), Fe(TPPS)^3-, was determined in sulfuric acid-ethanol-water media for 8.5-10.65M sulfuric acid at different temperatures. The overall reaction was the conversion of the complex Fe(TPPS)^3- into the diacid species H₄TPPS^2- without other spectrophotometrically important species being formed to an appreciable extent, as shown by three isosbestic points at 418, 462, and 563 nm. The rate was first order in the Fe(TPPS)^3- concentration. The pseudo-first-order rate constants k were exponentially dependent on the sulfuric acid concentration, and log k was linearly dependent on the Hammett acidity function –H₀. The average ΔH? and ΔS? values for five reaction media were 18.4 ± 1.4 kcal/mol and 19 ± 3 cal/°K · mol, respectively. The linear relationship between log k and (-H₀) and the approximately constant values of ΔH? ΔS? over the acid range investigated indicated that the same mechanism of demetallation was operative over this acid range. Because of the dependence of the pseudo-first-order rate constants on the acidity of the medium, the mechanism probably involves the addition of protons to pyrrole N atoms to assist in the breaking of iron (III)-nitrogen bonds.     

9, 10-Secocholesta-(5Z)-5,8(14), 10(19)-trien-3β-ol und 18-Nor-14β-methyl-9,10-secocholesta-(5E)-5, 10(19), 13(17)-trien-3β-ol,zwei neue Doppelbindungsisomere des Vitamins D3. Strukturelle Abwandlungen am Vitamin D3: 5. Mitteilung [1]

9,10-Secocholesta-(5 Z )-5,8(14),10(19)-triene-3β-ol and 18-Nor-14β-methyl-9,10-secocholesta-(5 E )-5,10(19), 13(17)-trien-3β-ol, two new double bond isomers of vitamin D₃ . Structural modifications of vitamin D₃: 5. Communication [1] The present paper reports the synthesis and structure elucidation of the two title compounds. Treatment of the 4-phenyl-1,2,4-triazolin-3,5-dione adducts of vitamin D₃ with BF₃O (C₂H₅)₂ and KOH/butanol yields these two new vitamin D₃ double bond isomers.     

Copper(I)‐Catalyzed Asymmetric [3+2]‐Cycloaddition of α‐Substituted Iminoesters with α‐Trifluoromethyl α,β‐Unsaturated Esters

Reported herein is an example of highly regio‐, diastereo‐ and enantioselective Cu(I)‐catalyzed intermolecular [3+2] cycloaddition reaction of α‐substituted iminoesters with α‐trifluoromethyl α,β‐unsaturated esters. This novel strategy provided a facile access to pyrrolidines with two skipped (aza)quaternary stereocenters including a CF₃ all‐carbon quaternary stereocenter. A broad substrate scope was observed and high yields (up to 94%) with excellent diastereoselectivity (up to >20 : 1 d.r.) and enantioselectivity (up to 98% ee) were obtained.