Derivatization of neutral steroids to enhance their detection characteristics in liquid chromatography–mass spectrometry

This review article underlines the detection-oriented derivatization of neutral steroids in liquid chromatography-mass spectrometry (LC-MS). Steroids have strong biological activity at very low concentrations in target tissues and, therefore, the analysis of steroids in body fluids or tissues is necessary to elucidate the nature of the many endocrine disease processes and thus be useful for diagnosis and treatment. LC-MS has recently been used for steroid analysis because of its specificity and versatility, but the ionization efficiencies of most steroids are relatively low for the different ionization methods. Derivatization enhances the ionization efficiencies of steroids, leading to high sensitivity and specific detection. For electrospray ionization MS the introduction of permanently charged moieties or easily ionizable moieties effectively increases the sensitivity of detection of steroids. The introduction of moieties with proton affinity or electron affinity enhances the analyte signals in positive and negative atmospheric pressure chemical ionization MS, respectively.     

The acid-catalyzed rearrangement of 1-N-allylindolines

Zinc chloride-catalyzed rearrangement of 1-N-allylindoline and 1-N-(2-methylallyl)indoline proceeds readily in refluxing xylene to give 7-allylindoline and 7-(2-methylallyl)indoline in 73% and 86% yields, respectively. The reaction of 1-N-2-butenylindoline and zinc chloride give rise to the mixture of 7-(1-methylallyl)indoline, 7-(cis- and trans-1-methyl-1-propenyl)indoline, and 7-(trans-2-butenyl)indoline. On the other hand, the similar reaction of 1-N-(3-methyl-2-butenyl)indoline with zinc chloride led to the formation of a mixture of 1,2,5,6-tetrahydro-4,4-dimethyl-4H-pyrrolo[3,2,1-ij]quinoline and 7-(3-methyl-2-butenyl)indoline.     

The structure of enopeptins A and B, novel depsipeptide antibiotics

The structures of enopeptins A and B, novel depsipeptide antibiotics with 1,3,5,7,9-decapentaene-1,10-dicarboxylic acid and 2-amino-3-hydroxycyclopent-2-enone in a side chain, were determined by chemical and spectroscopic means.     

Sulfur-bridged early-late heterobimetallics synthesized by incorporation of titanium,vanadium, and molybdenum into bis(hydrosulfido) templates of group 9 metals

Reactions of the bis(hydrosulfido) complexes [Cp*Rh(SH)(2)(PMe(3))] (1a; Cp* = eta(5)-C(5)Me(5)) with [CpTiCl(3)] (Cp = eta(5)-C(5)H(5)) and [TiCl(4)(thf)(2)] in the presence of triethylamine led to the formation of the sulfido-bridged titanium-rhodium complexes [Cp*Rh(PMe(3))(micro(2)-S)(2)TiClCp] (2a) and [Cp*Rh(PMe(3))(micro2-S)(2)TiCl(2)] (3a), respectively. Complex 3a and its iridium analogue 3b were further converted into the bis(acetylacetonato) complexes [Cp*M(PMe(3))(micro(2)-S)(2)Ti(acac)(2)] (4a, M = Rh; 4b, M = Ir) upon treatment with acetylacetone. The hydrosulfido complexes 1a and [Cp*Ir(SH)(2)(PMe(3))] (1b) also reacted with [VCl(3)(thf)(3)] and [Mo(CO)(4)(nbd)] (nbd = 2,5-norbornadiene) to afford the cationic sulfido-bridged VM2 complexes [(Cp*M(PMe(3))(micro2-S)(2))2V](+) (5a(+), M = Rh; 5b(+), M = Ir) and the hydrosulfido-bridged MoM complexes [Cp*M(PMe(3))(micro2-SH)(2)Mo(CO)(4)] (6a, M = Rh; 6b, M = Ir), respectively.     

Pd.H-C Interactions. Preparation and Structure of Orthometalated Tetranuclear Complexes of Palladium(II) and Platinum(II)

The reaction of 2-(1-naphthyl)benzothiazoline with palladium(II) acetate leads to helical mononuclear and orthometalated tetranuclear products. The molecular structures of mononuclear palladium(II) [Pd(H1-nabz)(2)] (1) (H(2)1-nabz = 2-N-(1-naphthylmethylideneamino)benzenethiolate), tetranuclear palladium(II) [Pd(4)(1-nabz)(4)] (2) and tetranuclear platinum(II) [Pt(4)(1-nabz)(4)] (3) have been determined by single-crystal X-ray diffraction method. Crystal data for complex 1 are as follows: a = 14.208(3) ?, b = 18.227(4) ?, c = 14.398(8) ?; beta = 94.55(3) degrees; V = 3717.0(23) ?(3); space group = P2(1)/n, Z = 4. Crystal data for the complex 2 are as follows: a = b = 15.798(3) ?, c = 23.728(4) ?; V = 5921.7(20) ?(3); space group = I4(1)/a, Z = 16 for the Pd(1-nabz) unit. Crystal data for the complex 3 are as follows: a = b = 15.496(2) ?, c = 24.348(3) ?; V = 5846.3(20) ?(3); space group = I4(1)/a, Z = 16 for the Pt(1-nabz) unit. The mononuclear palladium(II) complex reveals short ortho-hydrogen.palladium distances of 2.66(7) and 2.48(7) ?. These short distances and (1)H NMR studies provide a M.H-C interaction which can be regarded as a three-center four-electron interaction. The molecular structures of 2 and 3 confirm the formation of unusual tetranuclear compounds featuring a rare C,N,S-tridentate ligand derived from orthometalation of pendant side arm. The structural and chemical properties of the mononuclear palladium(II) complex 1 clearly suggest that 1 is a potential intermediate in the formation of the tetranuclear complex 2 by orthometalation reactions.     

A helical array of pendant fullerenes on a helical poly(phenylacetylene) induced by non-covalent chiral interactions

Novel [60]fullerene-based poly(phenylacetylene)s prepared by the copolymerization of achiral phenylacetylenes bearing a C(60) or crown ether pendant form a one-handed helix upon complexation with L- and D-alanine, yielding a helical array of the pendant fullerenes with a predominant screw-sense along the polymer backbone.     

Cyclization mechanism for the synthesis of macrocyclic antibiotic lankacidin in Streptomyces rochei

The lankacidin biosynthetic gene cluster in Streptomyces rochei strain 7434AN4 was found to span 31 kb of the giant linear plasmid pSLA2-L and contain a polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) hybrid gene (lkcA), type I PKS genes, and pyrroloquinoline quinone (PQQ) biosynthetic genes (lkcK-lkcO). Feeding of PQQ to a pqq mutant restored the lankacidin production, suggesting its crucial role in an oxidation process. However, formation of the 17-membered macrocyclic ring was not catalyzed by PQQ-dependent dehydrogenase (Orf23), but was by flavin-dependent amine oxidase (LkcE). Compound LC-KA05 isolated from an lkcE disruptant was an acyclic intermediate lacking the C2-C18 linkage. These results suggested a cyclization mechanism for the synthesis of the lankacidin macrocyclic skeleton.     

Quinolone analogues 6 [1‐5]. Synthesis of 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones

The reaction of the quinoxaline N‐oxides 7a,b with diethyl ethoxymethylenemalonate gave the 1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 8a,b , whose reaction with N‐bromosuccinimide or N‐chlorosuccinimide afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 9a‐d. The reaction of compounds 9a‐d with hydrazine hydrate resulted in hydrolysis and decarboxylation to provide the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 10a‐d , whose reaction with nitrous acid effected oxidation to furnish the 3‐halogeno‐4‐hydroxy‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 11a‐d , respectively. The reaction of compounds 11a‐d with hydrazine hydrate afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4‐ols 12a‐d , whose oxidation provided the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐d , respectively. Compounds 6a‐d had antifungal activities in vitro.     

Synthesis of N3-substituted uridine and related pyrimidine nucleosides and their antinociceptive effects in mice

Seventy eight N(3)-substituted derivatives of uridine (1), thymidine (2), 2'-deoxyuridine (3), 6-azauridine (4), 2',3'-O-isopropylideneuridine (5), and arabinofuranosyluracil (6) were synthesized and their antinociceptive effects were evaluated. N(3)-(2',4'-Dimethoxyphenacyl)uridine (1l), N(3)-(2',4'-dimethoxyphenacyl)2'-deoxyuridine (3l), and N(3)-(2',5'-dimethoxyphenacyl)arabinofuranosyluracil (6m) possessed 93, 86, and 82% of the antinociceptive effects tested by hot plate, respectively. The antinociceptive effects of three derivatives were 5.8, 5.4, and 5.1-folds of the effect of N(3)-phenacyluridine (1h) (16%), respectively. The structure-activity relationship of N(3)-substituted pyrimidine nucleosides was also discussed.     

Two stereoisomers of an S-bridged RhIII2PtII2 tetranuclear complex [{Pt(NH3)2}2{Rh(aet)3}2]4+ that lead to a discrete and a 1D RhIII2PtII2AgI structures by reacting with AgI (aet = 2-aminoethanethiolate)

An S-bridged RhIII2PtII2 tetranuclear complex having two nonbridging thiolato groups, [{Pt(NH3)2}2{Rh(aet)3}2]4+ ([1]4+), in which two fac(S)-[Rh(aet)3] units are linked by two trans-[Pt(NH3)2]2+ moieties, was synthesized by the 1:1 reaction of fac(S)-[Rh(aet)3] (aet = 2-aminoethanethiolate) with trans-[PtCl2(NH3)2] in water. Complex [1]4+ gave both the meso (DeltaLambda) and racemic (DeltaDelta/LambdaLambda) forms, which were separated by fractional crystallization. Of two possible geometries, syn and anti, which arise from the arrangement of two nonbridging thiolato groups, the meso and racemic forms of [1]4+ selectively afforded the anti and syn geometries, respectively. The DeltaLambda-anti and DeltaDelta/LambdaLambda-syn isomers of [1]4+ reacted with Ag+ using two nonbridging thiolato groups to produce a {RhIII2PtII2AgI}n) polymeric complex, {[Ag{Pt(NH3)2}2{Rh(aet)3}2]5+}n) ([2]5+), and a RhIII2PtII2AgI pentanuclear complex, [Ag{Pt2(mu-H2O)(NH3)2}{Rh(aet)3}2]5+ ([3]5+), respectively, which contain octahedral RhIII, square-planar PtII, and linear AgI centers. In [2]5+, each DeltaLambda-anti-[{Pt(NH3)2}2{Rh(aet)3}2]4+ tetranuclear unit is bound to two AgI atoms to form a one-dimensional zigzag chain, indicating the retention of the parental S-bridged structure in DeltaLambda-anti-[1]4+. In [3]5+, two Delta- or Lambda-fac(S)-[Rh(aet)3] units are linked by a [Pt2(mu-H2O)(NH3)2]4+ dinuclear moiety, together with an AgI atom, indicating that two NH3 molecules in [1]4+ have been replaced by a water molecule that bridges two PtII centers, while the parental DeltaDelta/LambdaLambda-syn configuration is retained. The complexes obtained were characterized on the basis of electronic absorption, CD, and NMR spectra, along with single-crystal X-ray analyses.