Synthese eines steroidischen 17 β-Pyrrolinons. Partialsynthetische Versuche in der Reihe der Herzgifte. 10.Mitteilung

Synthesis of a steroidal 17 β-pyrrolinone We describe the synthesis of 4′-(3 β-hydroxy-androst-5-ene-17 β-yl)-3′-pyrrolin-2′-one (6) starting from 3β-acetoxy-21-hydroxy-pregn-5-ene-20-one (1).     

Studies on furan derivatives. II. Preparation of α-substituted β-2-(5-nitrofuryl)vinylamines

α-Subslituted β-2-(5-nitrofuryl)viriylamines were synthesized from α-ary]-β-2-(5-nitrofuryl)-aeryloyl azides and N-[α-substituled β-2-(5-nitrofuryl)vinyl] pyridinium bromides.     

Friedel-crafts cyclisation—IV: Intramolecular vs intermolecular acylation with β-aryl derivatives of propionyl chloride in aromatic substrates

Studies on the aluminium chloride-catalysed behaviour of β-phenylpropionyl, β,β-diphenylpropionyl, and β,β,β-triphenylpropionyl chlorides in anisole and some other aromatic stubstrates under standardised conditions are discussed. β,β-Diphenylpropionyl chloride gave yields of up to 27% 3-phenylindan-1-one in anisole and is one of the most easily cyclised acid chlorides so far reported. β,β,β-Triphenylpropionyl is less easily cyclised in anisole to 3,3-diphenylindan-1-one and its transformation product 2,3-diphenylind-1-one. The expected open-chain ketone is completely decomposed into products of αβ-ketonic cleavage and a subsequent redox reaction. Differences in ratios of intermolecular to intramolecular acylation (now called o/c ratios) are discussed.In benzene, β-bis-(p-chlorophenyl)propionyl chloride gave, in addition to the previously noted β-bis-(p-chlorophenyl)propiophenone (48%), the folloowing compounds: 6-chloro-3-(p-chlorophenyl)indan-1-one (4%) (the intramolecular acylation product), β-(p-chlorophenyl)-β-phenylpropiophenone (2·3%), ββ-diphenylpropiophenone (0·5%), 3-(p-chlorophenyl)-indan-1-one (5·2%). The transformation processes are discussed. Aluminium chloride-catalysed β-aryl exchange in acid chlorides is reported for the first time, but β-aryl exchange does not occur in ββ-(or 3,3-)di-aryl derivatives of indan-1-one.     

2,4-Disubstituted Pyrrolo[2,3-d]pyrimidine α-D- and β-D-Ribofuranosides Related to 7-Deazaguanosine

Nucleobase-anion glycosylation (KOH, tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1), MeCN) of the pyrrolo[2,3-d]pyrimidines 4a – d with 5-O-[(1,1-dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribo-furanosyl chloride ( 5 ) gave the protected β-D -nucleosides 6a – d stereoselectively (Scheme 1). Contrary, the β-D -halogenose 8 yielded the corresponding α-D -nucleosides ( 9a and 9b ) apart from minor amounts of the β-D -anomers. The deprotected nucleosides 10a and 11a were converted into 4-substituted 2-aminopyrrolo[2,3-d]-pyrimidine β-D -ribofuranosides 1 . 10c , 12 , 14 , and 16 and into their α-D -anomers, respectively (Scheme 2). From the reaction of 4b with 5 , the glycosylation product 7 was isolated, containing two nucleobase moieties.     

水溶性显色型分子识别器-甲基红基乙二胺基羟丙基-β-环糊精

通过选择性氧化,将水溶性优良的羟丙基-β-环糊精转化为丙酮基羟丙基-β- 环糊精。再利用乙二胺分子作为柔性链和连接剂键连制得水溶性的甲基乙二胺基羟 丙基-β-环糊精。在甲基红基乙二胺基羟丙基-β-环糊精的稀水溶液中（6 * 10~ (-8) ～ 2 * 10~(-5) mol·dm~(-3))加入已烷等疏水性客体分子时,甲基红基团 可被掎到β-环糊精空腔外。若是在酸性介质中,甲基红基团还会同时发生偶氮基 团的质子化反应,并伴随颜色的变化（由黄色→红色）,该变色程度与客体分子的 外型、体积及极性等有关,从而起到分子检测器的作用。     

Structural Investigation of Hybrid Peptide Foldamers Composed of α-Dipeptide Equivalent β-Oxy-δ5-amino Acids

Due to their equivalent lengths, δ-amino acids can serve as surrogates of α-dipeptides. However, δ-amino acids with proteinogenic side chains have not been well studied because of synthetic difficulties and because of their insolubility in organic solvents. Recently we reported the spontaneous supramolecular gelation of δ-peptides composed of β(O)-δ⁵-amino acids. Here, we report the incorporation of β(O)-δ⁵-amino acids as guests into the host α-helix, α,γ-hybrid peptide 12-helix and their single-crystal conformations. In addition, we studied the solution conformations of hybrid peptides composed of 1:1 alternating α and β(O)-δ⁵-amino acids. In contrast to the control α-helix structures, the crystal structure of peptides with β(O)-δ⁵-amino acids exhibit α-helical conformations consisting of both 13- and 10-membered H-bonds. The α,δ-hybrid peptide adopted mixed 13/11-helix conformation in solution with alternating H-bond directionality. Crystal-structure analysis revealed that the α,γ⁴-hybrid peptide accommodated the guest β(O)-δ⁵-amino acid without significant deviation to the overall helix folding. The results reported here emphasize that β(O)-δ⁵-amino acids with proteinogenic side chains can be accommodated into regular α-helix or 12-helix as guests without much deviation of the overall helix folding of the peptides.     

Reaction of β-Oxodithioesters With Propargylamine: A Facile Entry to Novel 2-(Acylalkylidene)-5-(Methylene)Thiazolidines

Reaction of β-oxodithioesters derived from acyclic and cyclic ketones with propargylamine affords novel 2-(acylalkylidene)-5-(methylene)-thiazolidines in high yields by intramolecular nucleophilic attack of thiocarbonyl sulfur on the triple bond of the β-oxo-N-propargylthioamide intermediates.     

锰(III)5,10,15-三(五氟苯基)-Corrole配合物的DFT计算

在6-31G*水平上采用DFT(UB3LYP)方法对锰(III)5,10,15-三(五氟苯基)-corrole [(TPFC)MnIII]及其咪唑轴向配位加合物(TPFC)MnIII(Im)进行了几何结构全优化. 计算结果表明, 咪唑的配位作用不会改变其基态的高自旋(s=2)特性. (TPFC)MnIII与咪唑配位形成轴向加合物后, 其中心金属Mn原子偏离平面结构, 与corrole大环N4平均平面的距离达到0.02734 nm. NBO分析显示(TPFC)MnIII和(TPFC)MnIII(Im)中心金属锰的电子组态为(dxz)1(dyz)1(dz2)1(dx2-y2)1(dxy)0. (TPFC)MnIII(Im)前线分子轨道能级明显上升, 从其β-(LUMO+3)轨道可见咪唑配位N原子的py轨道与中心金属Mn原子dyz轨道形成了d-pπ轨道. TD-DFT计算发现, (TPFC)MnIII和(TPFC)MnIII(Im)电子光谱Q带的“四轨”特征比B 带明显; (TPFC)MnIII的CT带主要源自β-(HOMO-1)→β-(LUMO+5)和β-HOMO→β-(LUMO+4)的跃迁, (TPFC)MnIII(Im)的CT带则主要源自β-(HOMO-1)→β-(LUMO+3)和β-HOMO→β-(LUMO+4)的跃迁.     

1H NMR Studies of Hydroxy Protons of ASN- and Ser-Linked Disaccharides in Aqueous Solution

ABSTRACT

The hydroxy protons of β-D-GlcpNAc-(1→4)-β-D-GlcpNAc, β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, β-D-Galp-(1→3)-α-D-GalpNAc-O-Me and of β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser in aqueous solution have been investigated using ¹H NMR spectroscopy. The chemical shifts, coupling constants, temperature coefficients, exchange rates and NOEs have been measured. The O(3)H proton of β-D-GlcpNAc-(1→4)-β-D-GlcpNAc and β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, and the O(2')H proton of β-D-Galp-(1→3)-α-D-GalpNAc and β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser have values which differ significantly from the other hydroxy protons. Both these hydroxy protons are shielded when compared to those of the corresponding monosaccharide methyl glycosides. This shielding is attributed to the proximity of these protons to the O(5') oxygen and to the 2-acetamido group, respectively. In β-D-GlcpNAc-(1→4)-β-D-GlcpNAc and β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-N-Asn, the O(3)H proton has restricted conformational freedom with a preferred orientation towards the O(5') oxygen, and is protected from exchange with the bulk water through a weak hydrogen bond interaction with O(5'). In β-D-Galp-(1→3)-α-D-GalpNAc-O-Me and β-D-Galp-(1→3)-α-D-GalpNAc-O-Ser, the O(2')H is protected from exchange with the bulk water by the 2-acetamido group. The conformations of the disaccharides are not affected by the amino acid, and no interaction in terms of hydrogen bonding between the sugars and the amino acid residue could be observed.     

Synthesis of 5-(3-indolyl)oxazole natural products. Structure revision of Almazole D

The synthesis and utility of β-oxotryptamine and β-oxytryptophan ester synthons provide a convenient entry to 5-(3-indolyl)oxazole natural products leading to a structure revision of almazole D.     

Bifunctionalized allenes. Part XXI. Electrophilic cyclization and addition reactions of 3-(α- or β-hydroxyalkyl)-allenylphosphonates and allenyl phosphine oxides

Abstract

The present paper discusses the electrophilic cyclization and addition reactions of 3-(α- or β-hydroxyalkyl)-allenylphosphonates and phosphine oxides. Treatment of 3-(α- or β-hydroxy-alkyl)-allenylphosphonates with electrophiles takes place with 5-endo-trig cyclization and gives 2-methoxy-2,5-dihydro-1,2-oxaphosphole 2-oxides as a result of the neighboring phosphonate group participation in the electrophilic cyclization. On the other hand, 3-(α- or β-hydroxyalkyl)-alk-(1E)-en-1-yl phosphine oxides were prepared by chemo-, regio-, and stereoselective electrophilic addition to the C²-C³-double bond in the 3-(α- or β-hydroxyalkyl)-alka-1,2-dienyl phosphine oxides and subsequent attack of the external nucleophile (halide anion). The paper proposes a possible mechanism that involves electrophilic cyclization and addition reactions of the phosphorylated (α- or β-hydroxyalkyl)allenes.     

Copper(II)-catalyzed silyl conjugate addition to α,β-unsaturated conjugated compounds: Brønsted base-assisted activation of Si-B bond in water

A mild method for the installation of the dimethylphenylsilyl group on the β-carbon of electron-deficient olefins is reported. In the presence of a catalytic amount of copper(II) (1 mol %) and amine base (5 mol %) at rt, the transformation proceeds efficiently in water within 1.5-5 h to afford β-silylated products in yields of up to 90%.     

Formation of optically pure cyclic amines by intramolecular conjugate displacement

Intramolecular conjugate displacement (ICD) has been applied to the Morita-Baylis-Hillman adducts formed from (5S)-5-(l-menthyloxy)-2(5H)-furanone and aldehydes that carry a protected β- or γ-amino group. DIBAL-H reduction of the resulting ICD products releases optically pure six- or seven-membered cyclic amines having a stereogenic center α to nitrogen.     

Structural basis for the β-adrenergic receptor subtype selectivity of the representative agonists and antagonists

The β(3)-adrenegic receptor (β(3)-AR) selectivity over β(1)- and β(2)-ARs has been the most important aspect for successful therapeutic agents for obesity and type-II diabetes, as the concomitant activation of β(1)- and β(2)-ARs would lead to undesirable side effects, such as increased heart rate. In order to explore the structural basis for the β-AR subtype selectivity of agonists and anatagonists, a three-dimensional structure of until date unresolved β(3)-AR has been modeled, compared with the resolved X-ray structures of β(1)- and β(2)-ARs, and used to study its stereoselective binding with until-date known diverse classes of representative agonists and antagonist. The obtained binding structures and calculated prime molecular mechanics-generalized Born surface area (MM-GBSA) binding free energies consistently reveal that while the subtype selectivity is strongly governed by the residues present in the extracellular ends of TM3, TM5, TM6, TM7 helices and of the ECL2 domain, the binding affinity is governed by the conserved residues present in the deep pocket limiting the degree of conformational and rotational freedoms to the bound ligand. The study demonstrates that the key structural requirements for the β(3)-selectivity are: (i) a negatively ionizable group (NIG) for direct interaction with β(3)-specific residue R315(6.58), (ii) a linker (9-10 ? length) between the protonated amine and NIG, and (iii) a substituted aryl ring directly attached to the β-hydroxyl carbon. The new computational insights acquired in this study are expected to be valuable in structure-based rational design of high-affinity agonists and antagonists with pronounced β(3)-selectivity for successful therapeutic agents for type-II diabetes and obesity.     

A new disaccharide,glaucobiose from Chinese drug “Pai-ch'ien”: A comparison of 13C NMR with its diastereomeric isomer,strophanthobiose

The structure of a new disaccharide named glaucobiose (4) has been established, and the ¹³C NMR of its methyl β- (5) and α-glycoside (6), and that of methyl β-strophanthobioside (2) were studied.     

Das Carotinoidspektrum der Hagebutten von Rosa pomifera: Nachweis von (5Z)-Neurosporin; Synthese von (3R, 15Z)-Rubixanthin

Carotenoids from Hips of Rosa pomifera: Discovery of (5Z)-Neurosporene; Synthesis of (3R, 15Z)-Rubixanthin Extensive chromatographic separations of the mixture of carotenoids from ripe hips of R. pomifera have led to the identification of 43 individual compounds, namely (Scheme 2): (15 Z)-phytoene (1) , (15 Z)-phytofluene (2) , all-(E)-phytofluene (2a) , ξ-carotene (3) , two mono-(Z)-ξ-carotenes ( 3a and 3b ), (6 R)-?, ψ-carotene (4) , a mono-(Z)-?, ψ-carotene (4a) , β, ψ-carotene (5) , a mono-(Z)-β, ψ-carotene (5a) , neurosporene (6) , (5 Z)-neurosporene (6a) , a mono-(Z)-neurosporene (6b) , lycopene (7) , five (Z)-lycopenes (7a–7e) , β, β-carotene (8) , two mono-(Z)-β, β-carotenes (probably (9 Z)-β, β-carotene (8a) and (13 Z)-β, β-carotene (8b) ), β-cryptoxanthin (9) , three (Z)-β-cryptoxanthins (9a–9c) , rubixanthin (10) , (5′ Z)-rubixanthin (=gazaniaxanthin; 10a ), (9′ Z)-rubixanthin (10b) , (13′ Z)- and (13 Z)-rubixanthin (10c and 10d , resp.), (5′ Z, 13′ Z)- or (5′ Z, 13 Z)-rubixanthin (10e) , lutein (11) , zeaxanthin (12) , (13 Z)-zeaxanthin (12b) , a mono-(Z)-zeaxanthin (probably (9 Z)-zeaxanthin (12a) ), (8 R)-mutatoxanthin (13) , (8 S)-mutatoxanthin (14) , neoxanthin (15) , (8′ R)-neochrome (16) , (8′ S)-neochrome (17) , a tetrahydroxycarotenoid (18?) , a tetrahydroxy-epoxy-carotenoid (19?) , and a trihydroxycarotenoid of unknown structure. Rubixanthin (10) and (5′ Z)-rubixanthin (10a) can easily be distinguished by HPLC. separation and CD. spectra at low temperature. The synthesis of (3 R, 15 Z)-rubixanthin (29) is described. The isolation of (5 Z)-neurosporene (6a) supports the hypothesis that the ?-end group arises by enzymatic cyclization of precursors having a (5 Z)- or (5′ Z)-configuration.     

Bifunctionalized allenes. Part XXII. Coinage metal-catalyzed cycloisomerization of phosphorylated 3-(α- or β-hydroxyalkyl)allenes to 2-phosphoryl-2,5-dihydrofurans or 2-phosphoryl-5,6-dihydro-2H-pyrans

Abstract

The present paper discusses the coinage metal-catalyzed cycloisomerization reaction of phosphorylated 3-(α- or β-hydroxyalkyl)allenes. 3-(α- or β-Hydroxyalkyl)-allenylphosphonates and -allenyl phosphine oxides were smoothly converted into the 2-phosphoryl-2,5-dihydrofurans or 2-phosphoryl-5,6-dihydro-2Н-pyrans by using 5?mol % of coinage metal salts as catalyst in 5-endo-trig or 6-endo-trig cycloisomerization, respectively. Experimental conditions such as the type of the solvent, the reaction temperature, the mol % and the type of the catalyst and its influence on the yields and the reaction time of the cycloisomerization reaction of the phosphorylated 3-(α- or β-hydroxyalkyl)allenes were optimized.     

β-榄香烯-TEG-Re(CO)3配合物的合成、放射性标记及初步生物活性

以中草药有效成分β-榄香烯为起始原料, 经烯丙位的氯代反应及亲核取代反应, 成功地合成一种含水溶性基团TEG的三齿吡啶螯合剂, 并与稳定的三羰基铼配位, 得到了一种新的三羰基铼配合物, 在此基础上利用铼的放射性同位素Re-188进行了放射性标记. 反应中间体及最终化合物分别用IR, 1H NMR, HRMS, HPLC或元素分析等技术进行表征, 并对该化合物进行了初步的体外抗癌活性研究. β-Elemene-TEG-Re(CO)3配合物的合成、放射化学合成及体外抗癌活性评价, 为探讨榄香烯体内靶点和作用机制提供了可能, 并为最终开发基于β-榄香烯的放射性药物奠定了基础.     

The assignment of the 1H NMR signals to the methine bridge H-atoms in chlorophyll derivatives

Experiments are described which prove the assignments of the α- and β-protons in the ¹H NMR spectra of methyl phaeophorbide a ( 1 ) and methyl pyrophaeophorbide a ( 2 ). Because of the structural relationship between derivatives of the bacteriochlorophylls d ( 5 ) and 2 , dehydration of 5 results in a homologue mixture [2-(des-α-hydroxyethyl)-2-vinyl-bacteriomethyl phaeophorbide] d ( 6 ) of 2. Since the homologue substituents in 6 are located at C-4 and C-5 surrounding the β-H position, and since only one broad signal appears in its ¹H NMR spectrum, this is assigned to the β-proton. This experiment proves that the sequence of increasing shielding is β, α and δ in 6 ; and, therefore, the same sequence applies to the ¹H NMR spectra of 1 and 2 . This knowledge reveals that the product of electrochemical reduction of 1 in deuteromethanol is exclusively an α-chlorin-phlorin ( 8 ). In addition, the ¹H NMR spectrum of the 2-vinyl derivatives of the bacteriomethyl phaeophorbides c ( 7 ) shows the same broad signal at lowest field as does that of 6 . The sequence of increasing shielding is therefore, β, α. The influence of the additional δ-methyl group in 7 on the ring current is explained.     

ABOUT THE REACTION OF 2,3-DIBROMO-2-METHYL-N-(1-ADAMANTYL)-PROPANAMIDE WITH SODIUM TERT-BUTOXIDE. A COMPETITION EXPERIMENT

2,3-Dibromo-2-methyl-N-(1-adamantyl)propanamide (4), a precursor equally suited for the preparation of an α-lactam and a β-lactam, upon treatment with sodium tert-butoxide ether gives no α-lactam (5), but an excellent yield of the isomeric β-lactam, 1-(1-adamantyl)-3-bromo-3-methylazetidinone (6) as the only product. Repeating the experiment using a large excess of sodium tert-butoxide still leads to β-lactam 6 in 76.1% yield, but now accompanied by its dehydrobrominated derivative, β-lactam 7, in 17.4% yield, and no trace of α-lactam 5