Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition

(-)-Quinine-catalyzed intramolecular oxo-Michael addition (IMA) of 7-hydroxy-5-methoxy-8-tigloylcoumarins was developed for the enantioselective construction of 2,3-dimethyl-4-chromanone systems in the context of the asymmetric synthesis of anti-HIV-1 active Calophyllum coumarins. Combination of the IMA and MgI(2)-assisted demethylation of the 5-methoxy group along with isomerization of the formed chromanone systems as key steps successfully led to the concise synthesis of (+)-inophyllum B and (+)-calanolide A, possible candidates for AIDS drugs. Further examination of the asymmetric IMA with cinchona alkaloids lacking a methoxy group on the quinoline skeleton suggested the influence of the methoxy substituent on stereoselectivity at the stereogenic centers of the chromanone systems.     

Linear NiII-MnIII2-NiII tetramers: an oligomeric component of the MnIII2NiII single-chain magnets

Heterometallic linear tetramers [Mn(5-R-saltmen)Ni(pao)(bpy)(2)](2)(ClO(4))(4) (5-R-saltmen(2-) = N,N'-1,1,2,2-tetramethylethylene bis(5-R-salicylideneiminate); pao(-) = pyridine-2-aldoximate; bpy = 2,2'-bipyridine, R = H, 1; Cl, 2; Br, 3; MeO, 4) have been synthesized and structurally characterized. These compounds exhibit a [Ni(II)-NO-Mn(III)-(O)(2)-Mn(III)-ON-Ni(II)] skeleton where -ON- is an oximate bridge between Mn(III) and Ni(II) ions and -(O)(2)- is a bi-phenolate bridge between Mn(III) ions. These tetramers can be seen as oligomeric units of the heterometallic Mn(III)(2)-Ni(II) chain observed in a family of single-chain magnets (Clérac, R.; Miyasaka, H.; Yamashita, M.; Coulon, C. J. Am. Chem. Soc. 2002, 124, 12837. Miyasaka, H.; Clérac, R.; Mizushima, K.; Sugiura, K.; Yamashita, M.; Wernsdorfer, W.; Coulon, C. Inorg. Chem. 2003, 42, 8203.). Magnetic measurements on these tetramers confirm the nature of the magnetic interactions reported for the Mn(III)(2)-Ni(II) chains: a strong antiferromagnetic Mn(III)/Ni(II) coupling via the oximate bridge (J(Ni-Mn) ranges from -23.7 to -26.1 K) and a weak ferromagnetic Mn(III)/Mn(III) coupling through the bi-phenolate bridge (J(Mn-Mn) ranges from +0.4 to +0.9 K). These magnetic interactions lead to tetramers with an S = 2 ground state.     

Lannotinidines A-G, new alkaloids from two species of Lycopodium

Seven new Lycopodium alkaloids, lannotinidines A-G (1-7), have been isolated from the club moss Lycopodium annotinum and L. annotinum var. acrifolium. Stereochemistry of 1-7 was elucidated by combination of NOESY correlations and chemical transformation. Lannotinidines B-E (2-5) elevated NGF mRNA expression.     

MnIII2 (5-Rsaltmen)2NiII(pao)2(L)]2+: an S(T)=3 building block for a single-chain magnet that behaves as a single-molecule magnet

Mn(III)-Ni(II)-Mn(III) linear-type trinuclear complexes bridged by oximate groups were selectively synthesized by the assembly reaction of [Mn2(5-Rsaltmen)2(H2O)2](ClO4)2 (5-Rsaltmen2-=N,N'-(1,1,2,2-tetramethylethylene) bis(5-R-salicylideneiminate); R=Cl, Br) with [Ni(pao)2(phen)] (pao-=pyridine-2-aldoximate; phen=1,10-phenanthroline) in methanol/water: [Mn2(5-Rsaltmen)2Ni(pao)2(phen)](ClO4)2 (R=Cl, 1; R=Br, 2). Structural analysis revealed that the [Mn(III)-ON-Ni(II)-NO-Mn(III)] skeleton of these trimers is in every respect similar to the repeating unit found in the previously reported series of 1D materials [Mn2(saltmen)2Ni(pao)2(L1)2](A)(2) (L(1)=pyridine, 4-picoline, 4-tert-butylpyridine, N-methylimidazole; A=ClO4-, BF4-, PF6-, ReO4-). Recently, these 1D compounds have attracted a great deal of attention for their magnetic properties, since they exhibit slow relaxation of the magnetization (also called single-chain magnet (SCM) behavior). This unique magnetic behavior was explained in the framework of Glauber's theory, generalized for chains of ferromagnetically coupled anisotropic spins. Thus, in these 1D compounds, the [Mn(III)-ON-Ni(II)-NO-Mn(III)] unit was considered as an S(T)=3 anisotropic spin. Direct-current magnetic measurements on 1 and 2 confirm their S(T)=3 ground state and strong uniaxial anisotropy (D/k(B) approximately -2.4 K), in excellent agreement with the magnetic characteristic deduced in the study on the SCM series. The ac magnetic susceptibility of these trimers is strongly frequency-dependent and characteristic of single-molecule magnet (SMM) behavior. The relaxation time tau shows a thermally activated (Arrhenius) behavior with tau0 approximately 1x10(-7) s and Delta(eff)/k(B) approximately 18 K. The effective energy barrier for reversal of the magnetization Delta(eff) is consistent with the theoretical value (21 K) estimated from |D| S2T. The present results reinforce consistently the interpretation of the SCM behavior observed in the [Mn2(saltmen)2Ni(pao)2(L1)2](A)2 series and opens new perspectives to design single-chain magnets.     

Practical synthesis of a neuropeptide Y antagonist via stereoselective addition to a ketene

[Reaction: see text]. The synthesis of neuropeptide Y antagonist 1, currently under clinical investigation for the treatment of obesity, is described. The convergent synthesis from trans-spirolactone carboxylic acid intermediate 2a and aminopyrazole 3 is predicated on a stereoselective route to the former. The coupling reaction of ethyl 4-oxocyclohexanecarboxylate (10a) with lithiated isonicotinamide 11 was investigated in detail, but even optimized conditions only provided a 45:55 ratio of trans:cis isomers (12a:12b). While selective crystallization schemes were developed to isolate the thermodynamically less stable trans isomer 2a, improved stereocontrol was subsequentially achieved by the application of ketene chemistry. The ketene formation and quench was investigated under a variety of conditions aimed at maximizing the trans:cis ratio. Reacting a mixture of carboxylic acids 2a and 2b with POCl3 in THF, followed by concomitant addition of tert-butyl alcohol in the presence of TMEDA at 35 degrees C provided a 4:1 ratio of trans:cis tert-butyl esters (18a:18b) via in situ ketene formation. Ester hydrolysis, followed by selective crystallization of undesired 2b as the HCl salt, led to isolation of 2a in 47% overall yield. Aminopyrazole intermediate 3 was synthesized via the condensation reaction of 2-fluorophenylhydrazine hydrochloride (4a) with acrylonitrile derivative 5 in 65-70% yield. Coupling of advanced intermediates 2a and 3b via activation with thionyl chloride gave a 92% yield of 1.     

A highly stereoselective synthesis of the C10–C31 (BCDEF ring) portion of pinnatoxin A

An efficient, highly stereoselective synthesis of the C10–C31 (BCDEF ring) portion of pinnatoxin A has been achieved utilizing tandem double hemiketal formation/intramolecular hetero-Michael addition to construct the 6,5,6-dispiroketal (BCD ring) system and subsequent intramolecular ketalization to form the 5,6-bicycloketal (EF ring) system as key steps.     

Appearance of pure fluorocarbon micelles surveyed by fluorescence quenching of amphiphilic quinoline derivatives in fluorocarbon and hydrocarbon surfactant mixtures

A halide-sensitive fluorescence probe was utilized to evaluate the miscibility of fluorocarbon and hydrocarbon surfactants in aqueous micellar systems. The fluorescence of 6-methoxy-N-1,1,2,2-tetrahydroheptadecafluorodecylquinolinium chloride, FC10MQ, was quenched by halide ions dissociated from the surfactant. The fluorescence in micellar solutions showed an initially rapid decay. This suggests that halide ions effectively quench FC10MQ fluorescence at the micellar surface. The subsequent slow decay corresponds to the quenching of FC10MQ fluorescence in the aqueous bulk phase by the free counterions. The Stern-Volmer plots for fluorescence quenching gave a distinct break at the critical micelle concentration of the cationic surfactants. The abrupt increase in fluorescence quenching is attributed to the solubilization of the probe in the micelles. The fluorescence quenching behavior provides direct information about the immiscibility of fluorocarbon and hydrocarbon species in micelles, and the results indicate that almost pure fluorocarbon micelles appear in surfactants mixtures.     

Estimation of useful yields for electrospray droplet impact/secondary ion mass spectrometry (EDI/SIMS)

Useful yield for electrospray droplet impact/secondary ion mass spectrometry was estimated. The mixtures of C₆₀/rhodamine B and C₆₀/Aerosol OT were used as the samples for the positive and negative mode of operations, respectively. By assuming that (i) the desorption efficiencies are about the same for C₆₀, rhodamine B and Aerosol OT, and (ii) desorption of ionic compounds directly gives the secondary ion signals, the useful yields (i.e. total ions generated divided by the total molecules desorbed) for C₆₀ were estimated to be ~0.1. This value should be regarded as the upper limit because the neutralization of positive and negative ions in the plume and desorption of ionic compounds as neutral species are not taken into account. Copyright © 2012 John Wiley & Sons, Ltd.