Synthesis of 6-15N and 1-15N labeled adenosine monophosphates

A chemical synthesis of 6-¹⁵N and 1-¹⁵N AMPs from 5'-O-acety1-2',3'-O-isopropylideneinosine is reported.     

(苯并-15-冠-5)双Schiff 碱的合成

由苯并-15-冠-5经硝化、还原两步反应,制得4',5'-二氨基苯并-15-冠-5(2)。后者与水杨醛或其取代衍生物缩合,合成了一系列新的冠醚化双Schiff碱化合物1a～1h,经元素分析、IR、^1^HNMR和MS确证了其结构。     

13C, 15N coupling constants in substituted 1,2,4-triazines-4-15N

The ¹³C,¹⁵N coupling constants in three 1,2,4-triazine-4-¹⁵N derivatives and in a substituted pyrimidine-1-¹⁵N have been determined and are compared with those in pyridine and quinoline. Of special interest are the data of the 5-(2-dimethylamino-1-propenyl)-3,6-dimethyl-1,2,4-triazine-4-¹⁵N, since one observes a characteristic alternation of the absolute value of J(¹³C,¹⁵N) along the sidechain and a hitherto unobserved very large ¹³C,¹⁵N coupling constant through four bonds of 3·9 Hz, the origin of which is attributed to the influence of the lone pair orbital on the ¹⁵N at position 4.     

N,1-(15)N2]-2'-deoxyadenosines

[reaction: see text] An efficient route to deoxyadenosine derivatives labeled on both the amino group and nitrogen 1 is uncovered. First, 3',5'-di-O-acetyl-2'-deoxy-1-(2-nitrobenzenesulfonyl)inosine (2a) and only 1.1 equiv of (15)NH4Cl are used for labeling position 1 (1a) through the isolation of the open intermediate and its cyclization with DBU in anhydrous CH3CN. Inosine 1a is then converted to [N,1-(15)N2]-3',5'-di-O-acetyl-N6-benzoyl-2'-deoxyadenosine (5a, the precursor of 6a) via a Pd/dppf-catalyzed chloride-to-benzamide replacement, by using again only 1.1 equiv of the labeling source.     

Synthesis and properties of 5-(p-carbomethoxyphenyl)- 15-(p-dimethylaminophenyl)porphyrin

An unsymmetrically substituted 5,15-diarylporphyrin 1 , with p-dimethylamino and p-carbomethoxy substituents, was synthesized via a MacDonald condensation of aryldipyrromethane precursors 6 and 12 , which were prepared in good yield by three or four step procedures starting from ethyl 3,4-dimethyl-1H-pyrrole-2-carboxylate ( 2 ).     

Synthesis of 15- and 18-membered polythiamacrocylic ligands

Reaction of 1,8-dimercapto-3,6-dithioactane with oxa-, aza-, and thiadihaloderivatives under high dilution conditions in the presence of cesium carbonate, which acts as a template for the condensation reaction, produces 15- and 18-membered polythiamacrocyclic ligands in yields greater than 50%.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 660–662, May, 1989.     

New 15- and 18-Membered Polyunsaturated Macrocyclic Silicohydrocarbons

A multistep method is developed for the synthesis of polyunsaturated 15- and 18-membered macrocyclic silicohydrocarbons containing endocyclic CH = CH and CC groups in various structures. For the synthesis an intermolecular hydrosilylation reaction of specially synthesized polyfunctional silicohydrocarbons was applied.     

Stickstoff-15- und Gesamtstickstoff-Bestimmung durch Kopplung eines emissionsspektrometrischen N-15-Analysators mit einem automatischen N-Analysator

Zusammenfassung Die Kopplung eines emissionsspektrometrischen N-15-Analysators mit einem automatischen N-Analysator wird beschrieben. Im N-Analysator wird die Probe nach dem Dumas-Prinzip verbrannt und mit einem Wärmeleitfähigkeitsdetektor der Gesamtstickstoff-Gehalt bestimmt. Der Stickstoff wird nach der quantitativen Bestimmung durch selektive Adsorption an Molekularsieb 5 Å bei –90° C vom Helium-Trägergas abgetrennt. Nach der Desorption bei 300° C wird der Stickstoff zur emissionsspektrometrischen N-15-Analyse in das evakuierte QuarzEntladungsröhrchen überführt. Die Gesamtanalysenzeit beträgt ca. 30 min je Probe, die einen StickstoffGehalt von mindestens 200 g aufweisen sollte.Meinem Mitarbeiter, Herrn F. Gottselig, danke ich für die gute Zusammenarbeit bei der Verwirklichung dieses Vorhabens, Herrn Dr.Ing. Th. Grünewald für die Unterstützung bei der Lösung der mathematischen Probleme.     

15N nuclear magnetic resonance studies of [1-15N]nicotinamide adenine dinucleotides

The synthesis of [1-¹⁵N]nicotinamide adenine dinucleotide is described. Chemical shift data from ¹⁵N NMR studies are presented for the pyridine ring nitrogen of labeled NAD and related compounds. The results indicate a ¹⁵N label in the N-1 position to be highly sensitive to the redox-state of the pyridine moiety, with an upfield shift of over 100 ppm observed upon reduction of NAD⁺ to NADH. The feasibility of conducting ¹⁵N NMR studies of pyridine nucleotide binding to dehydrogenases is discussed.     

Determination of (15R)- and (15S)-15-methylprostaglandin E2 in human plasma with picogram per milliliter sensitivity by column-switching high-performance liquid chromatography

(15R)-15-Methylprostaglandin E2 (PGE2) is a pro-drug under evaluation for the treatment of acute upper gastrointestinal hemorrhage and gastrointestinal cytoprotection. It is converted in acid (e.g., gastric fluid) to its active 15S epimer. Both epimers are found in human plasma at low pg/ml levels following oral dosing. A high-performance liquid chromatographic (HPLC) method was developed for the simultaneous analysis of (15R)- and (15S)-15-methyl-PGE2 in human plasma. The method combined off-line solid-phase extraction and reversed-phase HPLC clean-up with panacyl bromide derivatization and subsequent analysis using a heteromodal column-switching technique. Assay linearity was demonstrated over a range of 10-200 pg/ml for both 15-methyl-PGE2 epimers (r greater than or equal to 0.995). There were no significant inter-day differences in assay results for either epimer at 50 and 25 pg/ml (p greater than 0.05), with pooled estimates of precision at these levels producing relative standard deviations of less than or equal to 8% and less than or equal to 12%, respectively. The method quantitation limit (signal-to-noise ratio 5:1) for both epimers was 10 pg/ml when processing 3 ml of plasma. The analysis procedure was shown to be useful for quantifying at or below 10% of the (15R)-15-methyl-PGE2 maximum plasma concentration following a 50-micrograms oral dose in three human volunteers. For the same three subjects, however, the plasma concentration of (15S)-15-methyl-PGE2 did not exceed the quantitation limit of 10 pg/ml.     

Asymmetric total synthesis of 14(R),15(S)-, 14(S),15(R)-, 14(R),15(R)-, and 14(S),15(S)-epoxyeicosatrienoic acids

The four chiral stereoisomers of 14,15-oxido-5Z, 8Z, 11Z-eicosatrienoic acid were synthesized. The absolute stereochemistry in each case was derived from an asymmetric epoxidation of E-2-octen-1-ol.     

Biosynthetic Production of [N2,1,3,7,9-15N]Guanosine and [1,3,7,9-15N]inosine and conversion into [N6,1,3,7,9-15N]adenosine for structure elucidation of RNA by heteronuclear NMR

A procedure was developed for the biosynthetic preparation of ¹⁵N-labelled guanosine and inosine through the action of a mutant Bacillus subtilis strain. Crude [N²,1,3,7,9-¹⁵N]guanosine and [1,3,7,9-¹⁵N]inosine were isolated from the culture filtrate by precipitation and anion-exchange chromatography (Scheme 1). No cell lysis and no enzymatic degradation was necessary. The per-isobutyrylated derivatives 1 and 2 were isolated from a complex mixture, purified by virtue of their different lipophilicity, and separated in three steps involving normal-and reversed-phase silica-gel chromatography. One litre of complex nutrient medium yielded 8.44 mmol of guanosine derivative and 2.84 mmol of inosine derivative with high average ¹⁵N enrichment (83.5 and 91.9 atom-%, resp.). [N⁶,1,3,7,9-¹⁵N]Adenosine ( 4 ) was obtained from 2′,3′,5′-tri-O-isobutyryl[1,3,7,9-¹⁵N]inosine ( 1 ) through the ammonolysis of its 1,2,4-triazolyl derivative with aqueous ¹⁵NH₃ (Scheme 2).     

Synthesis of Δ-15-deoxy-PG-J1 methyl ester and epi-Δ-15-deoxy-PG-J1

The synthesis of racemic Δ^12,14-15-deoxy-PG-J₁ is readily achieved in six steps employing as the key transformation a one-pot conjugate addition-Peterson olefination sequence using exo-2-trimethylsilyl-3a,4,7,7a-tetrahydro-4,7-methanoinden-1-one. Additionally a Noyori-type three-component coupling approach is employed for the synthesis of enantioenriched epi-Δ¹²-15-deoxy-PG-J₁ from 4(S)-tert-butyldimethylsilyloxycyclopent-2-enone.     

On the methylation of 5-(4-alkoxyphenyl)-15-(4-pyridyl)porphyrins

Mixed condensation of 3,3′-diethyl-4,4′-dimethyl-2,2′-dipyrrolylmethane 1 with 4-formylpyridine 2 and 4-alkoxybenzaldehyde 3 in acid medium and subsequent oxidation of the reaction mixture with DDQ gives, among other compounds, title compound 5 . An efficient methylation procedure of the pyridyl group in 5-(4-alkyoxyphenyl)-15-(4-pyridyl)porphyrins is described. Mixed condensation of 1 with N-methyl-4-formylpyridinium salt 9 and 3 yields among other compounds 5-(4-N-methylpyridiniumiodide)porphyrin 10 .     

Synthese eines kondensationsfähigen insulin-b15-20-hexapeptidderivates

The synthesis of the protected hexapeptide Boc-Leu-Tyr(Bzl)-Leu-Val-Cys(SEt)-Gly-OH with the sequence 15-20 of the insulin B chain suitable for fragment coupling is described.     

溶胶-凝胶非标记 CA15-3免疫传感器的研制与应用

采用溶胶-凝胶技术将乳腺癌抗体固定于电极表面,研制成用于检测乳腺癌抗原的非标记型溶胶-凝胶-抗体膜免疫传感器;用循环伏安法对电极的修饰过程进行表征,同时对乳腺癌抗原定量检测的可行性进行了探讨;随着抗体与抗原特异性反应的进行,形成的抗体-抗原免疫复合物使膜电位发生变化(△V),该变化的大小与溶胶-凝胶-抗体膜表面免疫反应进行的程度相关;本文以此为依据对CA15-3进行检测,在5～240U／mL范围内．△V／与lgCCA15-3呈良好的线性关系,线性相关系数r=O.998;该传感器响应迅速,灵敏度高,稳定性好,于4℃干态保存30d,其响应信号基本不变。     

Synthesis of the norjatrophane diterpene (-)-15-acetyl-3-propionyl- 17-norcharaciol

[reaction: see text] A scalable enantioselective synthesis of the nonnatural 17-norjatrophane diterpene 3-propionyl-15-acetyl-17-norcharaciol is described. Key C/C-connecting transformations are an Evans aldol reaction, an intramolecular carbonyl ene reaction, a Horner-Wadsworth-Emmons olefination, and a ring-closing metathesis for the formation of a 12-membered carbacycle.     

A new ornithine-containing lipid from Actinomyces no. 660-15

Summary From the sum of the cell lipids ofActinomyces No. 660-15 we have isolated a new ornithine-containing lipid the molecule of which is constructed of residues of L- and L--hydroxy fatty acids and L-ornithine.M. M. Shemyakin Institute of the Chemistry of Natural Compounds, Academy of Sciences of the USSR. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 145–153, March–April, 1972.