Additions of enantiopure alpha-sulfinyl carbanions to (S)-N-sulfinimines: asymmetric synthesis of beta-amino sulfoxides and beta-alphamino alcohols

The addition of the lithium anions derived from (R)- and (S)-methyl and -ethyl p-tolyl sulfoxides to (S)-N-benzylidene-p-toluenesulfinamide provides an easy access route to enantiomerically pure beta-(N-sulfinyl)amino sulfoxides. Stereoselectivity can be achieved when the configurations at the sulfur atoms of the two reagents are opposite (matched pair), thus resulting in only one diastereoisomer, even for the case in which two new chiral centers are created. The N-sulfinyl group primarily controls the configuration of the carbon bonded to the nitrogen, whereas the configuration of the alpha-sulfinyl carbanion seems to be responsible for the level of asymmetric induction, as well as for the configuration of the new stereogenic C-SO carbon in the reactions with ethyl p-tolyl sulfoxides. An efficient method for transforming the obtained beta-(N-sulfinyl)amino sulfoxides into optically pure beta-amino alcohols, based on the stereoselective non-oxidative Pummerer reaction, is also reported.     

(Z)-3-p-tolylsulfinylacrylonitrile as a chiral dienophile: diels-alder reactions with furan and acyclic dienes

The behavior of (Z)-3-p-tolylsulfinylacrylonitrile (1) as a chiral dienophile has been evaluated from its reactions with furan and acyclic dienes. Electrostatic interactions of the cyano group with the sulfinyl one restrict the conformational mobility around the C-S bond, thus controlling the pi-facial selectivity, which is almost complete in all cases, the approach of the diene from the less-hindered face of the dienophile (that bearing the lone electron pair) in the predominant rotamer being the favored one. The regioselectivity is also completely controlled by the cyano group. Additionally, the reactivity of compound 1 as well as its endo-selectivity are both higher than those observed for the corresponding (Z)-3-sulfinylacrylates, thus proving the potential of sulfinylnitriles as chiral dienophiles.     

Simultaneous quantitation of phenobarbitone and p-hydroxyphenobarbitone and their perdeuteroethyl analogues in biological fluids by combined gas chromatography-mass spectrometry

In order to develop 5-pentadeuteroethyl-5-phenyl barbituric acid as an alternative tracer in pharmacokinetic and metabolic studies of phenobarbitone, and to search for possible isotope effects associated with such labelling, we propose a gas chromatographic-mass spectrometric assay for simultaneous measurement of phenobarbitone, p-hydroxyphenobarbitone and their perdeuteroethyl analogues, using [1,3-15N2,2-13C] phenobarbitone as internal standard. These compounds were extracted from plasma (50 microliter) or urine (500 microliter) and pentylated according to Greeley's method. Linear calibration curves were obtained in the concentration range from 0.5 to 3 micrograms/ml. The interday precision, mean accuracy and detection limit were 0.77-5.28%, 99.99-100.80% and 0.03-0.05 microgram/ml, respectively. Results for plasma and urine concentrations, and pharmacokinetic parameters in humans, are presented to illustrate this method.     

Spin-singlet clusters in the ladder compound NaV2O5

The space group of alpha(')-NaV2O5 turns below T(c) = 34 K from Pmmn with all V sites equivalent, into Fmm2 with three independent vanadium sites per layer. This is incompatible with models of charge ordering into V4+ and V5+. Our structure determination indicates that the phase transition consists of a charge ordering with three distinct valence states, formally V4+, V4.5+, and V5+. The singlet formation is not associated with dimerization on the spin ladder, but with the formation of spin clusters. Finally, we ascribe the quadrupling of the c axis to the large polarizability of the V2O5 skeleton.     

Dependence of pulser driving responses on electrical and motional characteristics of NDE ultrasonic probes

Acoustic performance in ultrasonic transmitters can be improved by means of a suitable electrical driving response and matching/tuning networks. It is important to predict this electrical response, but doing so is not easy because it departs notably from the nominal pattern with the loading probes. In practice, the analysis of HV pulser spikes in NDE applications requires fairly complex models in the transient regime and, in addition, non-linear problems could arise, especially in the case of tuned transmitters. In this paper, the most relevant influences of loading characteristics of NDT ultrasonic probes on the pulser electrical driving responses are evaluated in time and frequency domains. Conventional pulse generators and typical NDE pulsers are considered. Driving responses are analysed across commercial ultrasonic probes and, alternatively, across similar purely electrical loads. Distinct influences on pulser responses from electrical and motional sections of the probes are identified. All these aspects are studied on the basis of experimental and computer results.     

Description of an individual patient methodology for calculating the cost-effectiveness of treatments for osteoporosis in women

Models of the cost-effectiveness of pharmaceutical interventions for the treatment of osteoporosis have traditionally adopted cohort-based approaches. We present a transition-state model to simulate the experience of individual patients, allowing the full patient history and residential status to influence the probabilities of future fractures at the hip, spine, wrist or proximal humerus. Alongside epidemiological data, we used systematic literature reviews of costs, utilities and efficacy to populate the model for a UK setting. We established a statistical relationship between the inputs and outputs of the individual patient model creating a near instantaneous emulation of the individual patient model. We undertook extensive sensitivity analyses to analyse the uncertainty in the estimated incremental cost per quality-adjusted life year due to uncertainty in the efficacy of the drugs. We provide illustrative results accompanied by individual and multi-interventional cost-effectiveness acceptability curves.