Stereoselective and Enantioselective Syntheses of the Four Stereoisomers of Muscol from (3RS)‐Muscone

Two trans stereoisomers of 3‐methylcyclopentadecanol (=muscol), (1R,3R)‐ 2 and (1S,3S)‐ 2 , were efficiently synthesized from (3RS)‐3‐methylcyclopentadecanone (=muscone; (3RS)‐ 1 ) by a highly stereoselective reduction (Scheme). L‐Selectride^® (=lithium tri(sec‐butyl)borohydride) was used, followed by the enantiomer resolution by lipase QLG (Alcaligenes sp.). The cis stereoisomers of muscol, (1S,3R)‐ 2 and (1R,3S)‐ 2 , were obtained by the Mitsunobu inversion of (1R,3R)‐ 2 and (1S,3S)‐ 2 , respectively (Scheme). The absolute configuration of (1R,3R)‐ 2 was determined by X‐ray crystal‐structure analysis of its 3‐nitrophthalic acid monoester, 2‐[(1R,3R)‐3‐methylcyclopentadecyl hydrogen benzene‐1,2‐dicarboxylate ((1R,3R)‐ 3b ), and by oxidation of (1R,3R)‐ 2 to (3R)‐muscone.     

Stereochemistry of alkyl 3-substituted 4-halotetrahydro-2-oxo-3-furancarboxylates: 2—1H and 13C NMR spectra

The ¹H NMR parameters of methyl 3-substituted cis-4-halotetrahydro-2-oxo-3-furancarboxylates are reported, with assignments of the ring protons based on solvent-induced changes in the vicinal trans coupling constants, ³J(H-4, H-5). Preferred conformations, ce with a pseudo-equatorial halogen for the cis isomers and ta with a pseudo-axial halogen for the trans isomers, have been suggested on comparison of the magnitudes of J(trans) and J(gem) in both series. The ³J(¹³CH₃, H-4) values measured for methyl cis-4-bromotetrahydro-3-methyl-3-furancarboxylate, methyl trans-4-bromotetrahydro-3-methyl-3-furancarboxylate and trans-3,4-dibromodihydro-3-methyl-2(3H)-furanone have confirmed the stereochemical assignments.     

Preparation of 3-Amino-3-Deoxy-2,4,5,6-Tetra-O-Methyl-D-Altronic Acid Hydrochloride,a Precursor in the Preparation of a Chiral β-Polyamide (Nylon 3 Analog)

ABSTRACT

3-Amino-3-deoxy-2,4,5,6-tetra-O-methyl-D-altronic acid hydrochloride was prepared from methyl 3-azido-3-deoxy-4,6-O-benzylidene-α-D-altropyranoside in seven steps. The key intermediate in this synthesis was the 3-acetamido-3-deoxy-2,4,6-tri-O-methyl-D-altrono-1,5-lactone which could be transformed, in one step, into methyl 3-acetamido-3-deoxy-2,4,5,6-tetra-O-methyl-D-altronate. However, attempts to open the 3-azido-3-deoxy-tri-O-methyl (or O-benzyl)-D-altrono-1,5-lactone intermediates gave a mixture of products, mostly, α,β-unsaturated carbonyl compounds. The 3-amino-3-deoxy-2,4,5,6-tetra-O-methyl-D-altronic acid could be transformed into the corresponding β-lactam, (3S,4R)-3-methoxy-4-(D-erythro-trimethoxypropyl) azetidine-2-one, which was further polymerized by anionic ring-opening polymerization giving poly[(2S,3R)-2-methoxy-3-(D-erythro-trimethoxypropyl) propanamide], a chiral nylon 3 analog.     

Carotenoids of the Carotenoprotein Asteriarubin. Optical Purity of Asterinic Acid

The carotenoid composition of the carotenoprotein asteriarubin ex the starfish Asterias rubens, determined by HPLC, comprised canthaxanthin ( 6 , 3% of total), all-trans-astaxanthin ( 1 , 14%), all-trans-7,8-didehydroastaxanthin ( 2 , 24%), all-trans-7,8,7′,8′-tetradehydroastaxanthin ( 3 , 43%) and 4-oxomytiloxanthin ( 7 , 10%). The previously unknown 4-oxomytiloxanthin was tentatively identified by the UV./VIS., 'H-NMR. spectra and MS. data. The optical purity was determined by HPLC. of the di-(?)-camphanates, by comparison with those of synthetic standards: 7,8,7′, 8′-tetradehydroastaxanthin (92% (3S, 3′S), 2% meso), 7,8-didehydroastaxanthin (89% (3S,3′S), 2% meso?), and astaxanthin (78% (3S,3′S), 14% (3R,3′S), and 5% (3R,3′R)). It is concluded that the acetylenic derivatives of astaxanthin in contrast to astaxanthin from marine animal sources are essentially pure (3S, 3′S)-isomers. This might reflect their probable metabolic formation by 4-oxo modification of acetylenic (3R,3′R)-carotenols ex Mytilus edulis in their diet.     

Calculation of j and jm symbols for arbitrary compact groups. III. Application to SO3 ⊃ T ⊃ C3 ⊃ C1

The methodology developed in earlier papers is used to compute the 6j symbols and 3jm factors that arise in the group chain SO₃ ? T ? C₁. The relevant character theory is given and the 2j and 3j symbols calculated. Selection rules are used to predict which j symbols or jm factors are necessarily zero, and then a set of 6j fundamentals computed for T. The complete set of primitive 6j symbols are then computed by application of the orthogonality and Racah backcoupling relations. Primitive 3jm factors are calculated for SO₃ ? T and T ? C₃ and, from these, all the 3jm factors for T ? C₃ and some of those for SO₃ ? T computed. A complete table of non-equivalent 6j symbols for T and 3jm factors for T ? C₃ is given, together with a table for SO₃ ? T of all 3jm factors with j ≤ 2.     

Synthesis of the (Z) and (E) isomers of 1,2-diaryl-3-methyl-4,5-dioxo-3-pyrrolidinecarboxylic acid esters. Structural assignment by nmr and mass spectroscopy

Reaction of N-benzylideneaniline, 1a , with 3-methyl-2-oxobutanedioic acid diethyl ester, 2a , produced isomeric 3-methyl-4,5-dioxo-1,2-diphenyl-3-pyrrolidinecarboxylic acid ethyl esters, 3a and 3b . The higher melting isomer, 3a , was shown to have the (Z) configuration by nmr spectroscopy. The (Z) and (E) isomers of 3-methyl-4,5-dioxo-1,2-diphenyl-3-pyrrolidinecarboxylic acid methyl esters, 3c and 3d , were prepared from 1a and 3-methyl-2-oxobutanedioic acid dimethyl ester, 2b . The higher melting isomer, 3c , was shown to have the (Z) configuration. Similarly, N-benzylidene-p-toluidine, 1b , reacted with 2a to form (Z) and (E) isomers of 3-methyl-4,5-dioxo-1-(4-methylphenyl)-2-phenyl-3-pyrrolidinecarboxlic acid ethyl esters, 3e and 3f . Assignment of the ¹³C carbonyl carbon nmr chemical shift was made by preparing 2-methyl-3-oxobutanedioic-1-¹³C acid diethyl ester, 4 , and from it the corresponding (Z) and (E) isomers of 3-methyl-4,5-dioxo-1,2-diphenyl-3-pyrrolidinecarboxylic ¹³C acid ester, 5a and 5b . The mass spectra of the (Z) isomers exhibit prominent ions corresponding to the masses of the Schiff bases used to make them, and ions corresponding to the loss of ArNCOCO from the parent ion. The (E) isomers 3b, 3d and 5b exhibit a prominent ion of mass 264; 3f gives mass 278, corresponding to the loss of the carboalkoxy group.     

Triaziridines. Part III. Triaziridine,azimine, and triazene: A SCF study of the energy and structure of N3H3-isomers

The portions of the N₃H₃ singlet potential energy surface corresponding to triaziridines ( 1 ), azimines ( 2 ) and triazenes ( 3 ) have been calculated by ab initio SCF using 3-21G, 6-31G, and 6-31G** basis sets. Minima and transition states were located by force gradient geometry optimization. The most important computation results are: (1) Triaziridines ( 1 ): The configuration at the 3 N-atoms is pyramidal. There are 2 stereoisomers, 1a and 1b . The c,t-isomer 1a has less energy than the c,c-isomer 1b . The 2 stereoisomerizations by N-inversion hve rather high activation energies. The N,N bonds in 1 are longer and weaker (STO-3G estimation) than in hydrazine. The N-homocycle 1 exhibits less ring strain than the C-homocycle cyclopropane or three-membered heterocycles. (2) Azimine ( 2 ): All 6 Atoms are in the same plane. There are 3 stereoisomers, 2a, 2b , and 2c . The order of ground state energies is (Z,Z) < (E,Z) ? (E,E). The 2 N,N bond lengths correspond to multiplicity 1½. The electronic structure of 2 corresponds to a 1,3-dipole with almost equal delocalization of the 4 π-electrons over all 3 N-atoms. The negative net charge at the central N-atom is much less than that at the terminal N-atoms. Azimines should behave as π-donors in complexation with transition metals (3) Triazene ( 3 ): All 6 atoms are in the same plane. There are 2 stereoisomers, 3a and 3b . The order of ground-state energies is (E) < (Z). The stereoisomerization proceeds as pure N-inversion. N-Inversion has a high energy barrier inversion at N(1) is faster than at N(2). One of the N,N bond lengths is typical for a double, the other for a single bond. The electronic structure of triazene 3 entails rather localized π- and p-electron pairs at N(1),N(2) and at N(3). Triazenes should behave as p-donors in complexation with transition metals. (4) -N₃H₃-Isomers: The order of ground-state energies is 3 < 2 < 1 . The energy differences between these constitutional isomers are much larger than between the stereoisomers of each. The [1,2]-H shifts for conversions of 2 to 3 and the [1,3]-H shift for tautomerization of 3 have relatively high activation energies; both shifts can be excluded as modes of thermal, unimolecular transformations.     

Stereoselective Reduction of `Capsanthol‐3′‐ones' (=3,6′‐Dihydroxy‐β,κ‐caroten‐3′‐ones) by Complex Hydrides

The (3R,5′R,6′R)‐ and (3R,5′R,6′S)‐capsanthol‐3′‐one (=3,6′‐dihydroxy‐β,κ‐caroten‐3′‐one; 4 and 5 , resp.) were reduced by different complex metal hydrides containing organic ligands. The ratio of the thus obtained diastereoisomeric (3′S)‐capsanthols 2 and 3 or (3′R)‐capsanthols 6 and 7 , respectively, was investigated. Four complex hydrides showed remarkable stereoselectivity and produced the (3′R,6′S)‐capsanthol ( 6 ) in 80 – 100% (see Table 1). The starting materials and the products were characterized by UV/VIS, CD, ¹H‐ and ¹³C‐NMR, and mass spectra.     

Beiträge zur Chemie des Phosphors. 134. Über die Triphosphane H(t-BuP)3H,Li(t-BuP)3Li und Me3Si(t-BuP)3SiMe3

Contributions to the Chemistry of Phosphorus. 134. On the Triphosphanes H(t-BuP)₃H' Li(t-BuP)₃Li, and Me₃Si(t-BuP)₃SiMe₃ The reaction of 1,3-diiodo-1,2,3-tri-tert-butyltriphosphane, I(t-BuP)₃I, with lithium aluminium hydride leads to 1,2,3-tri-tert-butyltriphosphane, H(t-BuP)₃H ( 1 ). 1 reacts with n-butyllithium to 1,3-dilithium-1,2,3-tri-tert-butyltriphosphide, Li(t-BuP)₃Li ( 2 ), which reacts further with trimethylchlorosilane yielding 1,3-bis(trimethylsilyl)-1,2,3-tri-tert-butyltriphosphane, Me₃Si(t-BuP)₃SiMe₃ ( 3 ). The triphosphanes 1, 2 and 3 could be isolated in a pure state. In solution 1 forms the threo, threo and the threo,erythro configurated diastereomers 1a and 1b in a ratio of about 2:1. 3 predominantly exists in form of the threo,erythro configurated diastereomer 3b by steric reasons.     

Alkyl Rearrangement of Derivatives of 2-Anilino-4,6-dialkoxy-1,3,5-triazines in the Solid- and Liquid-state

Abstract

2-Anilino-4,6-dimethoxy-1,3,5-triazine (13), 2-anilino-4,6-diethoxy-1,3,5-triazine (14), 2-(2′-nitoanilino) 4,6-dimethoxy-1,3,5-triazine (15) undergo alkyl rearrangement in the liquid-state, while 2-(4′-nito-anilino) 4,6-dimethoxy-1,3,5-triazine (16) undergoes methyl rearrangement in the solid-state. The crystal structure and thermal behavior of these compounds are described. 13 crystallizes in monoclinic P2₁/c space group, a = 11.030(4), b = 6.345(4), c = 16.315(4) Å, β = 90.76(3)°. The calculated density for Z = 4 is 1.351 Mg/m³. The number of unique reflections collected is 2092, and the final R = 0.0643 [I > 2σ(I)]. 14 crystallizes in triclinic P-1 space group, a = 7.700(2), b = 9.723(3), c = 10.154(3) Å, α = 78.78(3), β = 70.32(3), γ = 73.67(3)°. The calculated density for Z = 2 is 1.266 Mg/m³. The number of unique reflections collected is 2401, and the final R = 0.0561 [I > 2σ(I)]. 15 crystallizes in monoclinic P21/m space group, a = 11.020(3), b = 6.600(2), c = 8.409(3) Å, β = 99.72(3)°. The calculated density for Z = 2 is 1.527 Mg/m³. The number of unique reflections collected is 1153, and the final R = 0.0502 [I > 2σ(I)]. 16 crystallizes in monoclinic P21/c space group, a = 7.499(3), b = 21.846(5), c = 7.895(3) Å, β = 115.42(3)°. The calculated density for Z = 4 is 1.576 Mg/m³. The number of unique reflections collected is 2036, and the final R = 0.0757 [I > 2σ(I)].     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. V. Synthese von (3R, 3′R)-, (3S, 3′S)- und (3R,3′S; meso)-Zeaxanthin durch asymmetrische Hydroborierung. Ein neuer Zugang zu Optisch aktiven Carotinoidbausteinen. Vorläufige Mitteilung

Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. V. Synthesis of (3R, 3′R)-, (3S, 3′S)- and (3R,3′S; meso)-zeaxanthin by Asymmetric Hydroboration. A New Approach to Optically Active Carotenoid Building Units The synthesis of (3R, 3′R)-, (3S, 3′S)- and (3R,3′S; meso)-zeaxanthin ( 1 ), ( 19 ) and ( 21 ) is reported utilizing asymmetric hydroboration as the key reaction. Thus, safranol isopropenylmethylether ( 4 ) is hydroborated with (+)- and (?)-(IPC)₂BH to give the optically pure key intermediates 5 and 7 resp., which are transformed into the above-mentioned C₄₀-compounds.     

Metaboliten der 1,5-Dihydroimidazo[2,1-b]chinazolin-2(3H)-one. Synthese und Reaktionen einiger 1,5-Dihydro-3-hydroxyimidazo[2,1-b]chinazolin-2(3H)-one

Metabolites of 1,5-Dihydroimidazo[2,1-b ]quinazolin-2(3H)-ones. Preparation and Reactions of Some 1,5-Dihydro-3-hydroxyimidazo[2,1-b]quinazolin-2(3H)-ones Hydroxylated 1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-ones 2–4 and 6 were isolated as metabolites of imidazoquinazolinones 1a and 1b , respectively. The synthesis of 1,5-dihydro-3-hydroxy-3-methylimidazo[2,1-b]quinazolin-2(3H)-ones 3 , 4 , and 6 , and the preparation of some derivatives thereof is described.     

The Diyne Reaction of 3, 3′-Bis(phenylethynyl)-2, 2′-bithiophene Derivatives via Rhodium Complexes: A novel approach to condensed benzo[2, 1-b :3, 4-b′]dithiophenes

The syntheses of benzo-fused benzo[2, 1-b:3, 4-b′]dithiophenes 1 and benzo[2, 1-b:3, 4-b′:5, 6-c″]trithiophenes 2 are described. The treatment of easily available 3, 3′-bis(phenylethynyl)-2, 2′-bithiophene derivatives 5a and 6 (via Pd^II-catalyzed alkynylation of the corresponding 3, 3′-dibromo-2, 2′-bithiophenes; see Scheme 1) with chlorotris-(triphenylphosphine)rhodium(I) yields the corresponding cyclic rhodium complexes 7 (Scheme 2) which smoothly react with acetylenes and sulfur to give 1 and 2 in good yields (Schemes 3–5).     

The second order hyperpolarizability of cis azobenzene isomer

The second order hyperpolarizability of cis azobenzene isomer (γ_c) was obtained by measuring the third harmonic generation (THG) variation of an azobenzene doped polymer film when the film was optically pumped to create a large amount of cis isomers via photoisomerization. A steady state theory was developed to treat the THG intensity variation by considering the optical pump induced redistribution and reorientation of azobenzene in the polymer film and the contribution of cis isomer to the THG signal. The ratio of γ of cis and trans molecule, (γ_c/γ_t), was found to be 0.51. After the γ_t was obtained from the time-resolved optical Kerr effect (OKE) measurement, γ_c was deduced to be 5.6 × 10⁻³³ esu. The result shows that the optical nonlinearity of cis isomer is clearly not negligible.     

Synthese von optisch aktiven,natürlichen Carotinoiden und strukturell verwandten Naturprodukten. VII. Synthese von (3R)-3-Hydroxyretinol, (3R)-3-Hydroxyretinal und (3R)-3-Hydroxyretinsäure

Synthesis of optically active natural carotenoids and structurally related compounds. VII. Synthesis of (3R)-3-hydroxyretinol, (3R)-3-hydroxyretinal and (3R)-3-hydroxyretinoic acid The synthesis of (3R)-3-hydroxyretinol, ( 7 ), (3R)-3-hydroxyretinal ( 9 ) and (3R)-3-hydroxyretinoic acid ( 5 ) according to the building principle C₁₅ + C₅ = C₂₀ is reported utilizing the optically active C₁₅-phosphonium salt 2 and the C₅-aldehyde ester 3 .     

Eine Suche nach 3′-Epilutein ( = (3R,3′S,6′R)-β,ε-Carotin-3,3′-diol) und 3′, O-Didehydrolutein (=(3R, 6′R)-3-Hydroxy-β,ε-carotin-3′-on) in Eigelb,in Blüten von Caltha palustris und in Herbstblättern

Search for the Presence in Egg Yolk, in Flowers of Caltha palustris and in Autumn Leaves of 3′-Epilutein ( =(3R,3′S,6′R)-β,ε-Carotene-3,3′-diol) and 3′,O-Didehydrolutein ( =(3R,6′R)-3-Hydroxy-β,ε-carotene-3′-one) 3′.O-Didehydrolutein ( =(3R, 6′R)-3-hydroxy-β,ε-carotene-3′-one; 2) has been detected in egg yolk and in flowers of Caltha palustris. This is the first record for its occurrence in a plant. The compound shows a remarkable lability towards base; therefore, it may have been overlooked til now, because it is destroyed under the usual conditions of saponification of the carotenoid-esters. One of the many products formed from 2 with 1% KOH in methanol has been purified and identified as the diketone 3 ( =(3R)-3-hydroxy-4′, 12′-retro-β,β-carotene-3′,12′-dione). The identification of this transformation product from lutein might throw a new light on the metabolism of this important carotenoid in green plants. 3′-Epilutein ( =(3R,3′S,6′R)-β,ε-carotene-3,3′-diol; 1) was not detected in egg yolk, but is present besides lutein in flowers of C. palustris, thus confirming an earlier report of the occurrence of an isomeric (possibly epimeric) lutein (‘calthaxanthin’) in that plant [21]. We were not able to detect even traces of 1 or 2 in the carotenoid fraction from autumn leaves of Prunus avium (cherry), Parrotia persica, Acer montanum (maple) and yellow needles of Larix europaea (larch). α-Cryptoxanthin (4) , a very rare carotenoid, was isolated in considerable quantity for the first time from flowers of C. palustris.     

Crystal Structures of the Phosphorus‐Boron Adducts n‐Pr3P · BBr3 and I3P · BBr3

The structures of the phosphorus‐boron adducts n‐Pr₃P · BBr₃ (trigonal, space group P 4 c1, Z = 4, a = 11.5423(6), b = 11.5423(6) and c = 13.8066(7) Å) and I₃P · BBr₃ (orthorhombic, space group Pnma, Z = 4, a = 12.761(2), b = 11.427(1), c = 7.3728(7) Å) were determined by X‐ray crystallography. The P–B distance of 2.01(1) Å in I₃P · BBr₃ is significantly longer than the P–B bond in n‐Pr₃P · BBr₃ (1.95(1) Å). The different Lewis basicity of phosphorus halides, PX₃ (X = Cl, Br, I), and alkylphosphines is discussed. The charge transfer and the bond situation in these donor‐acceptor complexes is studied on the basis of NBO analysis. Selected frequencies of n‐Pr₃P · BBr₃ obtained by Raman and infrared spectroscopy are assigned and compared with the normal modes of I₃P · BBr₃.     

New Reactions of Amino-Functionalized 3-Vinyl-1H-indoles and Tetrahydropyridin-4-yl Analogues with Dienophiles

Reactions of 3-[2-(morpholin-4-yl)vinyl]-1H-indole ( 1 ), the 1,2-dihydro-9H-carbazole 2 , as well as the 3-(tetrahydropyridin-4-yl)-1H-indoles 3a and 3b with some carbo- and heterodienophiles are described. The scope and limitations of the synthetic utility of these amino- (or homoamino)-functionalized 3-vinyl-1H-indoles are reported and some MO calculations for the qualitative prediction of their reactivities are presented. The reactions gave rise to substitution products, redox products, Diels-Alder adducts, ene adducts, and Michael-type adducts (Schemes 2 and 3).     

Synthesis of New 3′-Deoxyribonucleosides Employing the Acid-Catalyzed Fusion Method

Coupling of 4,6-dichloro-1H-imidazo[4,5-c]pyridine (2,6-dichloro-3-deaza-9H-purine) ( 1 ) with 1,2-O-di-acetyl-5-O-benzoyl-3-deoxy-β-D -ribofuranose ( 2 ), employing the acid-catalyzed fusion method, is reported (Scheme 1). The condensation reaction was regioselective and gave the three N¹-glycosylation products 3 – 5 , whereas no N³-nucleosides were detected. Treatment of 3 – 5 with methanolic ammonia afforded the corresponding deprotected nucleosides 6 – 8 . Compounds 6 and 7 were assigned the structure of the β-D - and α-D -anomeric N¹-(3′-deoxyribo)nucleosides, respectively. The third derivative 8 proved to be the α-D -anomer of a 3′-deoxyarabinonucleoside deriving from epimerization at C(2) of the sugar. The 2-chloro- and N⁶-substituted derivatives 9 , 11 , and 13 of 3′-deoxy-3-deazaadenosine ( 10 ) and of its α-D -anomer 12 can be obtained from these versatile synthons (Schemes 2 and 3).     

Complexation Study and Spectrofluorimetric Determination of Pipemidic Acid with γ-Cyclodextrin

The fluorimetric characteristics of pipemidic acid (PIPE) have been investigated. It has been proven that the fluorescence emission band of pipemidic acid at 439 nm is significantly intensified in the presence of γ-cyclodextrin. The inclusional complexation between the antibacterial pipemidic acid and γ-cyclodextrin (γ-CD) has been studied. A 1:1 stoichiometry of the complex was established and its association constant was calculated by a nonlinear regression method, monitoring the changes in the fluorescence signal of pipemidic acid in the presence of γ-CD. According to the results obtained, a spectrofluorimetric method for the determination of PIPE has been proposed. The best limits of detection and quantification were obtained in presence of γ-CD, in acidic media. The dynamic range of the method was comprised between 0.18 and 1.40 μg/ml.