Inokosterone, an insect metamorphosing substance from Achyranthes fauriei : Absolute configuration and synthesis

Inokosterone, a phytoecdysone isolated from Achyranthes fauriei (Amaranthaceae), has been partially acetylated to give the 2,26-diacetate (4) which has been converted into methyl 5 - acetoxy - 4 - methylpentanoate (7), showing no apparent []_D, and 2β - acetoxy - 3β,14 - dihydroxy - 5β - pregn - 7 - ene - 6,20 - dione (8). Chemical and physiochemical studies have shown the configurations at C-20 and C-22 to be R. Inokosterone has thus been concluded to be a mixture of C-25 epimers of (20R,22R) - 2β,3β,14,20,22,26 - hexahydroxy - 5β - cholest - 7 - en - 6 - one (1). After the synthesis of the model compound, a C-25 epimeric mixture of (20R,22R) - 3β,20,22,26 - tetrahydroxy - 5 - cholestane (23), inokosterone has been synthesized via (20R) - 2β,3β,14,20 - tetrahydroxy - 20 - formyl - 5β - pregn - 7 - en - 6 - one (25) by Grignard reaction with 4 - (tetrahydrofuran - 2 - yloxy) - 3 - methylbutynylmagnesium bromide (15) followed by hydrogenation and hydrolysis. The use of an NMR shift reagent with the inokosterone acetates (9, 29) and the optical activity measurement of - methylglutaric acid (3) derived from inokosterone have established that inokosterone is a 1:2 mixture of the C-25 R and S epimers.     

Some intramolecular rearrangements when pentofuranoses are treated with diethylaminosulphur trifluoride (DAST)

Treatment of methyl 2,3-O-isopropylidene-β- -ribofuranoside with DAST gave a goodyield of 2,3-O-isopropylidene-5-O-methyl-β- -ribofuranosyl fluoride in which the methoxygroup had migrated from C-1 → C-5 and been replaced with retention of configurationby fluorine. The corresponding aldehyde when treated under similar conditions underwenta similar migration to give 5-deoxy-5-fluoro-2,3-O-isopropylidene-5-O-methyl-β- -ribofuranosylfluoride. A similar migration occurred with methyl 2′,3′-di-O-acetyl-β- -ribofuranosideand with acetyl 2,3-O-isopropylidene - -ribofuranose but not with 1,2,3-tri-O-acetyl- -ribofuranose. Thus the migration depends upon the migratory aptitude of thesubstituent at C-1 and the conformation of the furanose ring. Two ribofuranosyl fluorideswere used as starting materials from which to make nucleosides by the method of Noyoriand Hayoshi.     

A total synthesis of (±)-isocomene and (±) β-isocomene by an intramolecular ene reaction

The racemic sesquiterpenes isocomene 1 and β-isocomene 22 have been synthesized starting from 1,7-octadien-3-one 10 in a stereoselective manner. In the key step 12 → 13 (Scheme 5) the C-7, C-8-bond was formed by an intramolecular thermal ene reaction. Further transformations of 13 (Scheme 6) involved successively ring contraction 18 → 19, elimination 21 → 22 and olefin isomerization 22 → 1.     

Structure of Yononin A novel type of spirostanol glycoside

Two isomeric monomethyl ethers of yonogenin (25 ,5β-spirostane-2β,3-diol) have been synthesized and the 3-methyl ether identified as the aglycone of permethyl yononin. Thus, yononin, an - -arabinoside of yonogenin from the rhizome of Dioscorea Tokoro Makino, is shown to be a novel type of spirostanol glycoside in which the sugar moiety is attached to the hydroxyl group at C-2, and not at C-3, of the aglycone.     

Total asymmetric syntheses of 3- and 4-deoxy-hexoses and derivatives

(1S,4S)-7-Oxabicyclo[2.2.1]hept-5-en-2-one ((−)-5, a “naked sugar”) has been converted to (−)-(1R,4S,6S)-6-endo-benzyloxy-2-bromo-7-oxabicyclo[2.2.1]hept-2-ene ((−)-12) in a highly stereoselective fashion. Double hydroxylation of the C=C double bond of (−)-12, followed by acetylation and Baeyer-Villiger oxidation of the resulting -acetoxyketone (−)-14 afforded (−)-5-O-acetyl-2-O-benzyl-3-deoxy-β-D-arabino-hexofuranurono-6,1-lactone ((−)-15). This compound was converted readily into (+)-methyl 3-deoxy--D-arabino-hexofuranoside ((+)-6 and (+)-methyl 3-deoxy-β-L-xylo-hexofuranoside ((+)-7) and partially protected derivatives. (−)-15 was also converted into 4-deoxy-D-lyxo-hexopyranose (34) and several partially protected derivatives such as (+)-methyl 4-deoxy-2,3-O-isopropylidene--D-lyxo-hexopyranoside ((+)-8).     

Zur struktur des dimeren β-mercaptozimtaldehyds

Attempts to prepare β-thioketoaldehydes from β-chlorovinylaldehydes and sodium sulphide lead in the case of β-chlorocinnamic aldehyde and sodium sulphide to a dimer of β-mercaptocinnamic aldehyde. ¹ The structure of the dimer was proved by means of IR-, ¹H-NMR- and ¹³C-NMR-spectroscopy and established as bicyclo-[3.3.1]-5,7-diphenyl-3-hydroxy-2-oxa-6, 9-dithia-nonene-(7).     

Altered selectivity of reduction of steroidal carbonyls

The reduction of steroidal ketones in different solvents yielded different products. These conditions which altered the normal path, yielded a selective reduction of the Δ⁴-3 carbonyl without the concomitant reduction of the C-17 or C-20 ketones; this permitted a one step partial synthesis of 3β-hydroxy-Δ⁴-pregnen-20-one (I), 3β-hydroxy-5-pregnan-20-one (II), and of 3β,11β-dihydroxyandrostan-17-one (IV).     

Novel triterpenoid saponins from Mimusops elengi

Two novel triterpenoid saponins, mimusopin ( 3-O-β-D-glucopyranosyl-2β, 3β, 6β, 23-tetrahydroxyolean-12-en-28-oic acid 28-O--L-rhamnopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)[a-L-rhamnopyranosyl-(1→ 3)]--L-rhamnopyranosyl-(1→2)--L-arabinopyranoside)(1) and mimusopsin 3-O-[β-D-glucopyranosyl-(1→3)β-D-gluco-pyranosyl]-2β, 3β, 6β, 23-tetrahydroxyolean-12-en-28-oic acid 28-O--L-rhamnopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)--L-rhamnopyranosyl-(1→2)--L-arabinopyranoside (2) were isolated from the seeds of Mimusops elengi. Their structures were elucidated by a combination of 2D-NMR (COSY, HOHAHA, HETCOR, HMBC and NOESY), FAB-MS/MS and strategic chemical degradation. In addition, molecular mechanics and dynamics studies showed that the lack of a ¹³C glycosylation shift at the C-4 of the inner rhamnose in 1 could be correlated with distortion in the corresponding torsion angles.     

Excimer fluorescence in β-9,10-dichloroanthracene crystals

The fluorescence of single crystals of β-9,10-dichloroanthracene at 4.2 K consists solely of excimer emission (τ = 95 ± 5 ns). The absence of monomenc emission shows that excimer formation in this crystal is not a thermally activated process. This result is confirmed by excimer-excimer annihilation studies (γ(4.2 K) = 6 × 10⁻¹³, γ(298K) = 3 × 10⁻¹² cm³ s⁻¹).     

Solid-state photodimerization of cholest-4-en-3-one

Crystalline cholest-4-en-3-one undergoes solid-state dimerization by UV radiation to give two ring A - ring A connected dimers. No dimerization occurs in solution. The first dimer, characterized by a cyclobutane ring, is formed by connection of C-2 and C-3 of a moiety with C-5' and C-6' of another moiety, respectively. The latter dimer has a six-membered ketal ring formed by connection of C-2 with C-5' and of O, linked to C-3, with C-3'. The structures have been determined by spectroscopic means. X-ray analysis of title compound evidences the proximity of the axial H-2 of a molecule to the C-4' of a molecule in the upper layer. The transfer of the hydrogen and the connection between C-2 and C-5' might be the driving force of dimerization.     

Reaction of octafluorotoluene, 3,5-dichlorotrifluoropyridine, 3-chlorotetrafluoro-yridine and tetrafluoropyrimidine with alkali-metal oximates

Treatment of octafluorotoluene (2) with approximately one-molar equivalents of the oximates R¹R²C = NO~ M⁺ (R¹ = R²=Me;R¹ = R² = Ph; R¹ = Me, R² = Ph;M = Na) (6a-c) in diethyl ether gives 4-(R¹R²C = NO)C₆F₄CF₃ (7a-c) as the only isolated products. Corresponding reaction of 3,5-dichlorotrifluoropyridine (3) with the oximates 6a-c affords 4-and 2-(R¹R²C = NO)C5F₂C12N (8a-c) and (9a-c), respectively (4-/2ratios at −35 °C: 65:35; 30:70; 12:88) ; the lithium oximates (R¹ = R² =Ph ; R¹ = Me, R² = Ph; M = Li) (6d) and (6e) give comparable results. With 3-chlorotetrafluoropyridine (4), treatment with sodium oximate 6c gives 4-(PhCMe = NO)-3-ClC₅F₃N (10) and 2-(PhCMe = NO)-5ClC₅F₃N (11) (ratio 44:56 at −35 °C). Such competition between S_NAr attack of these alkali-metal oximates at the C-4 and C-2 positions of chlorofluoropyridines 3 and 4 can be rationalized by invoking chelation of an alkali-metal cation with ring nitrogen in the transition state leading to formation of an orthio-quinonoidal σ-complex. Exclusive initial attack at the C-4 ring site appears to occur in the reaction of tetrafluoropyrimidine (5) with oximates 6a and 6c to afford 4-(MeC = NO)C₄F₃N₂ (12a) and 4-(PhCMe=NO)C₄F₃NN₂ (12b), respectively; Some further attack on product 12b by oximate 6c at the C-6 site takes place to give the disubstituted derivative 4,6-(PhCMe=NO)₂C₄F₂N₂ (13).     

Modified cyclodextrin polymers as selective ion carriers for Pb(II) separation across plasticized membranes

In the present work the hydrophobic β-cyclodextrin (β-CD) polymers have been used as macrocyclic ion carriers for separation of Pb(II), Zn(II), and Cu(II) ions from dilute aqueous solutions by transport across polymer inclusion membranes. The β-CD polymers were prepared by cross-linking of β-CD with 2-(1-docosenyl)-succinic anhydride derivatives in anhydrous N,N-dimethylformamide in the presence of NaH. The metal ions were transported from aqueous solutions containing heavy metal ions through plasticizer triacetate membranes with dimer and polymer β-CD derivatives into distilled water. The selectivity of lead(II) over other metal ions in the transport through polymer inclusion membrane was very high, especially for dimer cyclodextrin carrier. In the case of competitive transport of Pb(II), Cu(II), and Zn(II) ions through plasticized immobilized membranes the selectivity of process is controlled via formation of ion pairs of β-CD hydroxyl groups with metal cations. The polymer and dimer of β-CD linked by 2-(1-docosenyl)-derivative used as ionic carriers for competitive transport of metal ions show preferential selectivity order: Pb(II)  Cu(II) > Zn(II). Application of ion carriers mixtures (β-CD polymers and palmitic acid) causes the increase of Pb(II) maximal removal from dilute aqueous solution. The weight-average molecular weight (M_W) and the chemical structure of the β-CD polymers were determined using high-performance size exclusion chromatography with refractive index detector, and ¹H NMR spectroscopy.     

(Z)-1-methoxy-4-(diphenylphosphino) but-1-ene-3-yne: A versatile synthon for unsymmetrically substituted (diphenylphosphino) diacetylene derivatives

An efficient synthesis of Ph₂P-C≡C-C≡C-Li, 1, was found, starting from commercially available (Z)-1-methoxybut-1-ene-3-yne and its diphenylphosphino derivative 2. The lithio compound 1 was condensed with electrophiles to give Ph₂P-C≡C-C≡C—Σ (Σ = SiR₃, SnR₃, B(NⁱPr)₂) 3. Compound 2 was easily transformed into the phosphonium salt 6 and the phosphine oxide 7 using MeI and H₂O₂ respectively. Derivatives 3 (Σ = SiMe₃, SnMe₃) are reactive at phosphorus and at the Σ group; complexation with W(CO)₅THF gave the expected derivatives W(CO)₅Ph₂P-C≡C-C≡C—Σ (Σ = SiMe₃, SnMe₃), 10, and in the case of Σ = SnMe₃, coupling reaction between Ph₂P-C≡-C-C≡C-SnMe₃, 3c, and (η⁵-IC₅H₄)Mn(CO)₃ in the presence of PdCl₂(CH₃CN)₂ as a catalyst gave the complex 11, Ph₂P-C≡C-C≡C-(η⁵-C₅H₄)Mn(CO)₃.     

Structural and spectral studies of N-2-(pyridyl)-, N-2-(3-, 4-, 5-, and 6-picolyl)- and N-2-(4,6-lutidyl)-N′-2-thiomethoxyphenylthioureas

Structures of the following compounds have been obtained: N-(2-pyridyl)-N′-2-thiomethoxyphenylthiourea, PyTu2SMe, monoclinic, P2₁/c, a=11.905(3), b=4.7660(8), c=23,532(6) Å, β=95.993(8)°, V=1327.9(5) ų and Z=4; N-2-(3-picolyl)-N′-2-thiomethoxyphenyl-thiourea, 3PicTu2SeMe, monoclinic, C2/c, a=22.870(5), b=7.564(1), c=16.941(4) Å, β=98.300(6)°, V=2899.9(9) ų and Z=8; N-2-(4-picolyl)-N′-2-thiomethoxyphenylthiourea, 4PicTu2SMe, monoclinic P2₁/a, a=9.44(5), b=18.18(7), c=8.376(12) Å, β=91.62(5)°, V=1437(1) ų and Z=4; N-2-(5-picolyl)-N′-2-thiomethoxyphenylthiourea, 5PicTu2SMe, monoclinic, C2/c, a=21.807(2), b=7.5940(9), c=17.500(2) Å, β=93.267(6)°, V=2893.3(5) ų and Z=8; N-2-(6-picolyl)-N′-2-thiomethoxyphenylthiourea, 6PicTu2SMe, monoclinic, P2₁/c, a=8.499(4), b=7.819(2), c=22.291(8) Å, β=90.73(3)°, V=1481.2(9) ų and Z=4 and N-2-(4,6-lutidyl)-N′-2-thiomethoxyphenyl-thiourea, 4,6LutTu2SMe, monoclinic, P2₁/c, a=11.621(1), b=9.324(1), c=14.604(1) Å, β=96.378(4)°, V=1572.4(2) ų and Z=4. Comparisons with other N-2-pyridyl-N′-arylthioureas having substituents in the 2-position of the aryl ring are included.     

A highly stereoselective synthesis of a key intermediate of 1β-methylcarbapenems employing the reformatsky reaction of 3-(2-bromopropionyl)-2-oxazolidone derivatives

Reaction of sterically crowded achiral 3-(2-bromopropionyl)-2-oxazolidone derivatives with (3 ,4 )-4-acetoxy-3-[( )-1-( -butyldimethylsilyloxy)ethyl]-2-azetidinone in the presence of zinc dust in refluxing tetrahydrofuran was found to give the 1β-methyl substituted β-lactams as major products (at most, β:=95:5). The major products were readily converted into the key intermediate of 1β-methylcarbapenems.     

Synthesis and molecular structure of the optically active organoaluminium dimer (S)-(—)-(S)-(—)- [(C6H5)CH(CH3)NHA1(CH3)2]2

Reaction of the optically active primary amine (S)-(—)--methylbenzylamine with trimethylaluminium in heptane affords the crystalline organoaluminium dimer (S)-(—)-(S)-(—)-[(C₆H₅)CH(CH₃)NHA1(CH₃)₂]₂. Isolated as large, colourless, extremely air-sensitive prismatic crystals, the title compound crystallizes in the orthorhombic space group P2₁2₁2₁ with unit cell parameters a = 8.406(3), b = 15.505(4), c = 17.547(5) Å, V = 2287 ų and p = 1.03 g cm⁻³ for Z = 4. Least-squares refinement based on 1477 observed reflections converged at R = 0.056, R_w = 0.058. Methane was eliminated during the course of the reaction due to cleavage of A1---C and N---H bonds resulting in an asymmetric A1₂N₂ fragment at the core of the organoaluminium dimer. The mean A1---C bond distance in the dimethylaluminium units is 1.930(8), while the mean A1---N bond distance is 1.950(5) Å. Specific rotation ([]_D²⁵ in CH₂C1₂)of the dimer is determined to be - 20.6°.     

E-2-Benzylidenebenzocycloalkanones. IV. Studies on transmission of substituent effects on C NMR chemical shifts of E-2-(X-benzylidene)-1-tetralones, and -benzosuberones. Comparison with the C NMR data of chalcones and E-2-(X-benzylidene)-1-indanones

Single substituent parameter (SSP) and dual substituent parameter (DSP) analyses were applied to study the transmission of substituent effects on selected ¹³C NMR chemical shifts of the cyclic chalcone analogues, E-2-(4′-X-benzylidene)-1-tetralones (2) and E-2-(4′-X-benzylidene)-1-benzosuberones (3). In order to study how the geometry of the cyclic chalcone analogues affects the transmission of substituent effects similar investigations with the respective chalcones (4) were also performed. The results obtained earlier with the five-membered analogue E-2-(4′-X-benzylidene)-1-indanones (1) were also involved in the comparisons. Geometry optimization of the unsubstituted 1a, 2a, 3a and 4a as well as the substituted 2 and 3 was performed by ab initio quantum chemical calculations. Both SSP and DSP analyses reflected that resonance effects contribute more to the chemical shift of C- (C2), while inductive effects primarily affect that of C-β (C10) of the enone moiety of all the four series. This latter effect, however, is far not as pronounced as that of the former one. It was found that DSP analysis data (ρ_F and ρ_R values) of transmission of substituent effects on the δC2 data can serve as a measure of choice to study the conformation (planarity) of the investigated enones in the four series.     

Unusual Knoevenagel condensations of 16a-substituted-16-methylene-17-keto-steroids

A Knoevenagel condensation between 3β-acetoxy-16-pyrrolidinylmethylenandrost-5-en-17-one (8c) and an excess of malononitrile led unexpectedly to 3β-acetoxyandrost-5-eno-[17,16-c]-1′,6′-dicyanoaniline (12a) as the major product and 3β-acetoxy-16-pyrrolidinylmethylen-17-dicyanomethylenandrost-5-ene (11a) as the minor product. Knoevenagel reactions of other 16a-substituted-16-methylen-17-keto steroids were studied to evaluate the scope and mechanism of the reaction.     

Structural, spectral and thermal studies of N-2-(4-picolyl)- and N-2-(6-picolyl)-N′-(2-chlorophenyl)thioureas and N-2-(6-picolyl)-N′-(2-bromophenyl)thiourea

N-2-(4-picolyl)-N′-2-chlorophenylthiourea, 4PicTu2Cl, monoclinic, P2₁/c, a=10.068(5), b=11.715(2), β=96.88(4)°, and Z=4; N-2-(6-picolyl)-N′-2-chlorophenylthiourea, 6PicTu2Cl, triclinic, P-1, a=7.4250(8), b=7.5690(16), c=12.664(3) Å, =105.706(17), β=103.181(13), γ=90.063(13)°, V=665.6(2) ų and Z=2 and N-2-(6-picolyl)-N′-2-bromophenylthiourea, 6PicTu2Br, triclinic, P-1, a=7.512(4), b=7.535(6), c=12.575(4) Å, a=103.14(3), β=105.67(3), γ=90.28(4)°, V=665.7(2) ų and Z=2. The intramolecular hydrogen bonding between N′H and the pyridine nitrogen and intermolecular hydrogen bonding involving the thione sulfur and the NH hydrogen, as well as the planarity of the molecules, are affected by the position of the methyl substituent on the pyridine ring. The enthalpies of fusion and melting points of these thioureas are also affected. ¹H NMR studies in CDCl₃ show the NH′ hydrogen resonance considerably downfield from other resonances in their spectra.     

Comparison of calculated DFT/B3LYP and experimental C and O NMR chemical shifts, ab initio HF/6-31G* optimised structures, and single crystal X-ray structures of some substituted methyl 5β-cholan-24-oates

Single crystal X-ray structures (monoclinic space group P2₁) for methyl 3-oxo-5β-cholan-24-oate and methyl 3,12-dioxo-5β-cholan-24-oate have been solved and compared with HF/6-31G* optimised structures. In the crystalline packings the side chains are connected with weak OC(sp³)HO-type of interactions between C25–H and C24–O–C25 and the keto ends with weak C(sp³)HO=C-type of interactions between C4–H and O=C3. The orientations of the side chains, which steric configurations are of great importance to the biological activity of the molecules, are compared with the experimental structure of methyl 3-hydroxy-5β-cholan-24-oate. Probable reasons for the observed differences are discussed. In addition, ¹³C and ¹⁷O NMR chemical shifts of methyl 3-oxo-5β-cholan-24-oate and methyl 3,12-dioxo-5β-cholan-24-oate as well as the epimeric methyl 3-hydroxy-5β-cholan-24-oate and methyl 3β-hydroxy-5β-cholan-24-oate have been calculated (DFT/B3LYP/6-311G*) and compared with the experimental values by linear regression analyses. In general, the correspondence between the theoretical and experimental parameters is good or excellent.