Conversion from (-)-delta-6,1-3,4-trans-tetrahydrocannabinol in (-)-delta-1,2-3,4-trans-tetrahydrocannabinol

Successive treatment of (?)-Δ^6,1-3,4-trans-tetrahydrocannabinol with hydrochloric acid/zinc chloride and potassium-t-amylate gives (?)-Δ^1,2-3,4-trans-tetrahydrocannabinol in quantitative yield.     

Synthese und Struktur von S{NAs(tBu)2[Os3(CO)11]}2 Das erste Schwefeldiimid mit trans,trans-Konfiguration im Festkörper

Synthesis and Structure of S{NAs(^tBu)₂[Os₃(CO)₁₁]}₂. The First Sulphur Diimide with trans,trans Configuration in the Solid State In the reaction of bis(di-tert-butylarsino) sulphur diimide, S(NAs^tBu₂)₂, with the cluster Os₃(CO)₁₁(NCCH₃) either one or two [Os₃(CO)₁₁] units can be added to the sulphur diimide — according to the molar ratio — yielding Os₃(CO)₁₁As(^tBu)₂NSNAs^tBu₂ ( 1 ) or S{NAs(^tBu)₂[Os₃(CO)₁₁]}₂ ( 2 ), respectively. The title compound μ-[(trans,trans)-bis(di-tert-butyl-arsino)sulphur diimide-As,As]-bis(undecacarbonyl-triangulo-triosmium) ( 2 ) is also obtained upon thermolysis of 1 in refluxing octane; its structure was elucidated by X-ray crystallography. Complex 2 is the first sulphur diimide with a trans,trans configuration in solid state. The trans,trans configuration is forced by the bulky substituents. 2 crystallises with deuterochloroform (1:1) in the monoclinic space group C2/c: a = 25.887(3), b = 8.684(1), c = 26.357(4) Å, β = 103.34(1)°, Z = 4. Due to special positions the SN₂ moiety (inversion center) and the chloroform molecule (twofold axis) are disordered statistically. The S?N bond lengths amount 1.50(2) Å on the average, the angle at, sulphur (111(2)°) is smaller in comparison with open-chained sulphur diimides with the cis, trans and cis,cis configuration. The angles a t the K atoms are enlarged (131(2) and 135(2)°), respectively. With exception of small torsions around the S?N bonds the principle of coplanarity for sulphur diimides is also fulfilled for t,he trans, trans form. The amino residues occupy equatorial positions in the triosmium clusters. I n the triosmium triangle two bonds are almost equal in length (2.891(1) and 2.884(1) Å, respectively), the third Os? Os bond is somewhat enlarged (2.939(1) Å).     

Synthesis of (-)-delta6,1-3,4-trans-tetrahydrocannabinol, as well as (+)-delta 6,1-3,4-trans-tetrahydrocannabinol

Acids, such as p-toluenesulfonic acid, mediate the direct formation of optically active (?)-Δ6,1-3,4-trans-tetrahydrocannabinol from (+)-cis-or (+)-trans-p-menthadiene-(2,8)-ol-(1) and olivetol.     

Synthesis of (-)-11 Hydroxy-delta8-6a, 10a-trans-tetrahydrocannabinol

When (?)-Δ⁸-6a, 10a-trans-THC (THC = Tetrahydrocannabinol), in the form of its diacetate, was irradiated in the presence of oxygen and a sensitizer, followed by reduction with NaBH₄, three allylic alcohols were formed: (?)-8α-and (?)-8β-hydroxy-Δ^9,11-THC (proportion 3:1) and (?)-9α-hydroxy-Δ^7,8-THC. Acetylation of the epimeric 8-hydroxy-compounds with Ac₂O/pyridine gave the corresponding diacetates. When (?)-Δ⁸-6a, 10a-trans-THC, in the form of its tetrahydropyranyl derivative, was heated with m-chloroperbenzoic acid, the two epimeric 8,9-epoxides were formed in equal amounts. These compounds, on treatment with butyllithium, afforded (?)-8α- and (?)-8β-hydroxy-Δ^9,11- 6a, 10a-trans-THC-tetrahydropyranylether. After removing the protecting group and treatment with Ac₂O/pyridine the same diacetates, as formed by photooxygenation of (?)-Δ⁸-THC-acetate, were obtained as a 1:1-mixture. On heating these epimeric diacetates to 290° they underwent allylic rearrangement to (?)-11-acetoxy-Δ⁸-THC-acetate. From this (?)-11-hydroxy-Δ⁸-6a, 10a-trans-THC was obtained by treatment with LiAlH₄.     

Chiral nucleophilic glycine and alanine synthons: nickel(II) complexes of Schiff bases of (S)-N-(2,4,6-trimethylbenzyl)proline (2-benzoylphenyl)amide and glycine or alanine

A new chiral auxilliary, (S)-N-(2,4,6-trimethylbenzyl)proline (2-benzoylphenyl)amide, has been synthesised as a potential building block for the preparation of chiral synthons of amino acids. The nickel(II) complex of its Schiff base derivative with glycine has been methylated with 97% d.e. (diastereomeric excess), whilst the nickel(II) complex of its Schiff base derivative with (RS)alanine has been ¹³C-methylated with 66% d.e.     

Terpene compounds as drugs. XVI. Characterization of the anabolic 19-nortestosterone 17 -trans, trans- and -cis, trans-homofarnesate

19-Nortestosterone 17β-trans, trans- and -cis, trans-homofarnesate 1 and 2 have been prepared and characterized. Their structure and configuration were identified by mode of formation, elemental analyses, IR. and particularly by NMR. spectra.     

Isomeric compositions in amide acids and poly(amic acid)s derived from 1-(trifluoromethyl)-2,3,5,6-benzenetetracarboxylic dianhydride

Two different poly(amic acid)s were synthesized by the polycondensations of 1-(trifluoromethyl)-2,3,5,6-benzenetetracarboxylic dianhydride (CF3DAN) with p-phenylene diamine and benzidine. In addition, an amide acid model compound was prepared from CF3DAN and aniline. Isomeric units in the poly(amic acid)s as well as the amide acid were investigated by ¹H and ¹³C-nuclear magnetic resonance (NMR) spectroscopies. Spectroscopic results indicate that the major isomeric component was a CF3-meta-isomeric unit centered on the aromatic carbon substituted with the trifluoromethyl group. In particular, the amide acid compound was determined to be composed of 80 mol % CF3-meta-isomer and 20 mol % H-meta-isomer. Therefore, for the poly(amic acid)s, the minor isomeric component is speculated to be a H-meta-isomeric unit rather than a para-isomeric unit. The result might result mainly from the strong electron-withdrawable and bulky trifluoromethyl substituent in the CF3DAN monomer. The strong electron withdrawability might significantly enhance the reactivities of the adjacent carbons in the monomer to the nucleophilic attack of the amino nitrogen in the aniline and diamines, and consequently overcome the role of the bulkyness, ultimately leading to the amide acid and poly(amic acid)s rich with the CF3-meta-isomeric unit. In addition, a portion of the imide form was detected in the dried AN-CF3DAM-AN amide acid. Thus, the formation of imide linkage might be involved in a small portion for the dried poly(amic acid)s. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 1755–1765, 1998     

First total syntheses of (±)-3-aza-11-selena and (±)-3-aza-11-tellura steroids

An efficient synthesis of 11-selena and 11-tellura steroids bearing a pyridine as an A ring was achieved via an intramolecular Diels-Alder cycloaddition of o-quinodimethanes, which were generated from a 3-azabicyclo[4.2.0]octa-1,3,5-trien-7-one ketal. The major isomer matches the trans-anti-trans ring configuration of natural products. Finally, the vinyl groups of the synthesized 11-hetero steroids have been oxidized by the Wacker process in good yields. The characteristic ¹H and ¹³C NMR spectroscopic features of the synthesized compounds are reported.     

Photoinduced reactions of Cr(CO)3-coordinated N-cyanoazepine: [6 + 4] cycloaddition with conjugated dienes

The tricarbonyl(N-cyanoazepine)chromium(0) complex (2) is formed when (MeCN)₃Cr(CO)₃ is treated photochemically with N-cyanoazepine (1). U.v photolysis of Cr(CO)₃( ⁶-N-cyanoazepine)chromium(0) (2) and conjugated dienes [1,3-butadiene (3), trans-1,3-pentadiene (4), trans,trans-2,4-hexadiene (5)] in PhMe give the [6 + 4]cycloadducts, tricarbonyl{ ^4:2-11-N-cyano-11-azabicyclo[4.4.1]-undeca-2,4,8-triene}chromium(0) complexes (6–8). The -complex (2) and these new bicyclic compounds (6–8) were purified by chromatography, recrystallized, isolated as analytically pure crystalline solids in moderate yields and characterized by mass, i.r. and n.m.r. spectroscopy. The heterobicyclotrienes, 11-N-cyano-11-azabicyclo[4.4.1]undeca-2,4,8-triene (9–11), were isolated from the complexes (6–8) by heating in PhMe, and their structures were assigned by the same spectroscopic methods.     

A novel strategy for the preparation of the injectable PET/CT radiopharmaceutical (-)-[11C]-(1R,2S)-meta-hydroxyephedrine ((-)-[11C]HED

Positron emission tomography (PET) had been applied in clinical early diagnosis of various tumors and other diseases. The methylated synthetic conditions of (-)-[¹¹C]-(1R,2S)-meta-hydroxyephedrine ((-)-[¹¹C]HED), considered as one of the most important radiopharmaceuticals for PET, were optimized through single factor and orthogonal design methods. Here, we reported an improved purification protocol. The radiochemical yields of the final product were over 45% (decay-corrected and based on [¹¹C]methyl iodide) (n?=?50). The radiochemical purities and chemical purities were over 99% (n?=?50) and 97% (n?=?50), respectively. The automatic radiosynthesis procedure of (-)-[¹¹C]HED with relatively high radiochemical yield was convenient and reliable.

     

Conformational studies of poly(cis-5-ethyl-D-proline)

Two possible conformations for poly(cis-5-ethyl-D -proline) have been identified and characterized by using combinations of ¹H- and ¹³C-NMR, CD, and ORD spectroscopic techniques. Both forms have helical conformations similar to those of poly(L -proline) characterized by different amide bonds (cis and trans). However, the carbonyl group of the amide in poly(cis-5-ethyl-D -proline) form II (trans) seems to be closer to perpendicular orientation with respect to the helical axis than in poly(L -proline) form II. The pyrrolidine ring conformation of form I (cis) is probably β⁺γ^?-puckered, whereas for form II it is probably β⁺-puckered in nature. The side-chain ethyl groups prefer to adopt anti conformations to the C₅? H bond, or prefer to have χ = 180°, regardless which of the two forms poly(cis-5-ethyl-D -proline) may like to assume. The experimental results agree well with our previous theoretical conformational energy calculations.     

Metal Complexes with Macrocyclic Ligands. Part XXIX.. Structural and kinetic studies of two isomeric Cu2+ complexes with 1,4-dimethyl-8-[2-(2-pyridyl)ethyl]-1,4,8,11-tetraazacyclotetradecane

The synthesis and complexation properties of 1,4-dimethyl-8-[2-(2-pyridyl)ethyl]-1,4,8,11-tetraazacyclotetra-decane ( 2 ) are described. This ligand forms with Cu²⁺ two complexes, one of which has been characterized by X-ray structure analysis. The structural, spectral, and kinetic studies indicate that the two Cu²⁺ complexes are isomers with the macrocycle in the trans-III and trans-I configuration. The rate of the interconversion of the trans-I isomer to the thermodynamically more stable trans-III species is proportional to [OH^?]. A mechanism for this reaction is proposed.     

Stereoselective Synthesis of Frans-(E)-N-{2-[4-(3,4-Dichlorophenyl)but-2-En-2-Yl]Cyclohexyl}Pyrrolidine as an Alkene Mimetic of the Arylacetamide Analgesics

Diethylaluminum trimethylsilylacctylide reacted stereospecifically with the mesylate of trans-2-(N- pyrrolidinyl)cyclohexanol (2) to give trans-N-[2-(trimethylsilylacetylcnyl)cyclohexyl]pyrrolidine (3). The trimethylsilyl group in 3 was displaced with a 3,4-dichlorobenzoyl group to give ynone 4, which then underwent 1,4-addition with lithium dimethylcuprate to give trans enone 6 and its cis isomer 5 in a ratio 5:1. Reduction of the enones with NaBHVCeCl₃ resulted in cis and trans allylic alcohols 9 and 10. Both 9 and 10 were successfully deoxygenated with Znl₂-NaCNBH₃ reducing system to give trans-(E)-N-{2-[4-(3,4- dichlorophenyl)bul-2-en-2-yl]cyclohexyl}pyrrolidine (11) as the onty product. Olefin 11, a carbon-carbon double bond isostere of the prototypek-selective opioid analgesic U-50488, showed a 10³ fold reduction in K-affinity (K_ik = 1.6 × 10⁴ nM vs 15 nM for U-50488).     

Schiff-Basen aus 1,3-Dicarbonylverbindungen und Triaminen und ihre Fe (III)-, Co (III)-, Ni(II)- und Cu(II)-Komplexe

Schiff bases of 1,3-dicarbonyl compounds with triamines and their Fe(III), Co(III), Ni(II) and Cu(II) complexes The preparation of new hexadentate ligands obtained by the reaction of cis, cis-1,3,5-triaminocyclohexane (tach) or 1,1,1-tris (aminomethyl)ethane (tame) with an 2-ethoxymethylidene-1,3-dicarbonyl compound as well as their Fe(III), Co(III), Ni(II) and Cu(II) complexes is reported. Fe(III) and Co(III) yield neutral complexes with an octahedral N₃O₃-coordination sphere, Ni(II) and Cu(II) complexes with a square-planar coordination-sphere. In the later complexes one of the bidentate branches of the ligand is not deprotonated and stays uncoordinated.     

Synthesis of(+)-(2S, 6S)-trans-α-Irone and of(-)-(2S, 6S)-trans-γ-Irone

A 3:1 mixture of (+)-(2S, 6S)-trans-α-irone ((+)-1) and (?)-(2S, 6S)-trans-γ-irone (?)-2) has been synthesized with ca. 70% e. e. by the ene reaction of (?)-(S)-3 and but-3-yn-2-one.     

Liquid chromatographic and mass spectral analysis of 1-(3,4-methylenedioxyphenyl)-3-butanamines, homologues of 3,4-methylenedioxyamphetamines

The 1-(3,4-methylenedioxyphenyl)-3-butanamines (HMDAs) are prepared via reductive amination of the corresponding ketone with a series of low molecular weight alkylamines. These amines are homologues of the N-substituted 3,4-methylenedioxyamphetamines (MDAs). Compounds of the HMDA series have UV absorption properties similar to the MDAs because both series contain the same 3,4-methylenedioxyphenyl chromophore. The HMDAs are separated via reversed-phase liquid chromatographic methods using a C18 stationary phase and an acidic aqueous acetonitrile mobile phase. The mass spectra of these potential designer drugs are very similar to the spectra of the MDA homologues having the same N-substituent.     

The syntheses of 4b,5a-dihydro-5H-benzo[3,4]-phenanthro[1,2-b]azirine and 1a,11b-dihydro-6,11-dimethyl-1H-benz[3,4]anthra[1,2-b]azirine

The syntheses of the K-imine derivatives of carcinogenic benzo[c]phenanthrene and 7,12-dimethylbenz-[a]anthracene are described. Treatment of trans-5-azido-5,6-dihydrobenzo[c]phenanthren-6-ol ( 3 ) and trans-6-azido-5,6-dihydrobenzo[c]phenanthren-5-ol ( 5 ) with thionyl chloride yielded the corresponding β-chloro azides, which in turn, were reacted with lithium aluminium hydride to give 4b,5a-dihydro-5H-benzo[3,4]-phenanthro[1,2-b]azirine ( 2 ). In a similar manner trans-5-azido-5,6-dihydro-7,12-dimethylbenz[a]anthracen-6-ol ( 11 ) and trans-6-azido-5,6-dihydro-7,12-dimethylbenz[a]anthracen-5-ol ( 13 ) were transformed to the respective chloro azides and, converted into 1a,11b-dihydro-6,11-dimethyl-1H-benz[3,4]anthra[1,2-b]azirine ( 10 ).     

Biosynthesis of δ-Jasmin Lactone ( = (Z)-Dec-7-eno-5-lactone) and (Z,Z)-Dodeca-6,9-dieno-4-lactone in the Yeast Sporobolomyces odorus

(all-Z)-(9,10,12,13,15,16-²H₆)Octadeca-9,12,15-trienoic acid ( = α-linolenic acid; D₆- 4 ) was synthesized to investigate the biochemical formation of linolenic-acid-derived aroma compounds in cultures of the yeast Sporobolomyces odorus, using an established gas chromatographic/mass spectrometric (GC/MS) method. Three compounds were identified as labeled: (Z)-dec-7-eno-5-lactone (δ-jasmin lactone), (Z,Z)-dodeca-6,9-dieno-4-lactone, and (2E,4Z)-hepta-2,4-dienoic acid. Both lactones were biosynthesized mostly under conservation of the initial configuration from their corresponding oxygenated linolenic-acid intermediates. The application of (13S,9Z,11E,15Z)-13-hydroxy(9,10,12,13,15, 16-²H₆)octadeca-9,11,15-trienoic acid (D₆- 7 ) as a OH-functionalized precursor of δ-jasmin lactone allowed to gain insight into the stereochemical course of the biosynthesis to both enantiomers of this lactone. In this experiment, 88.3% of the metabolized labeled precursor was transformed under retention of the original configuration of the (R)-enantiomer. This investigation is also a contribution to a better understanding of the C?C bond isomerization steps which took place during the β-oxidative degradation of the substrate.     

Die thermische Umlagerung von 2-(Buta-1′,3′-dienyl)-phenolen in 2-Alkyl-2H-chromene; Beispiele für aromatische [1,7a]- und [1,5s]sigmatropische Wasserstoffverschiebungen

2-(1′-cis,3′-cis-)- and 2-(1′-cis,3′-trans-Penta-1′,3′-dienyl)-phenol (cis, cis- 4 and cis, trans- 4 , cf. scheme 1) rearrange thermally at 85–110° via [1,7 a] hydrogen shifts to yield the o-quinomethide 2 (R ? CH₃) which rapidly cyclises to give 2-ethyl-2H-chromene ( 7 ). The trans formation of cis, cis- and cis, trans- 4 into 7 is accompanied by a thermal cis, trans isomerisation of the 3′ double bond in 4. The isomerisation indicates that [1,7 a] hydrogen shifts in 2 compete with the electrocyclic ring closure of 2 . The isomeric phenols, trans, trans- and trans, cis- 4 , are stable at 85–110° but at 190° rearrange also to form 7 . This rearrangement is induced by a thermal cis, trans isomerisation of the 1′ double bond which occurs via [1, 5s] hydrogen shifts. Deuterium labelling experiments show that the chromene 7 is in equilibrium with the o-quinomethide 2 (R ? CH₃), at 210°. Thus, when 2-benzyl-2H-chromene ( 9 ) or 2-(1′-trans,3′-trans,-4′-phenyl-buta1′,3′-dienyl)-phenol (trans, trans- 6 ) is heated in diglyme solution at >200°, an equilibrium mixture of both compounds (～ 55% 9 and 45% 6 ) is obtained.     

Synthese des (R)-trans-11-Hydroxy-8-dodecensäure-lactons (Recieifeiolid)

Synthesis of Recifeiolide The synthesis of the mould metabolite recifeiolide (VIII), a 12-membered ring lactone, is described. 1,3-Butandiol was resolved with (?)-camphanic acid via (R)-1-iodo-3-butanol (II) into (R)-3-hydroxybutyl triphenyl phosphonium iodide (III). Wittig condensation of the phosphorane derived from III with methyl 8-oxo-octanoate (V) led to the methyl trans-11-hydroxy-8-dodecenoate (VI). The corresponding hydroxy acid VII was transformed into the S-(2-pyridyl) carbothioate which cyclizes under the influence of silver ion to the lactone VIII. With (?)-(R)-1,3-butandiol (I) as starting material the naturally occurring (+)-(R)-recifeiolide (VIII) is produced in 70% yield from VII.