Enantiodiscrimination of racemic electrophiles by diketopiperazine enolates: asymmetric synthesis of methyl 2-amino-3-aryl-butanoates and 3-methyl-aspartates

Enolates of (S)-N,N′-bis-(p-methoxybenzyl)-3-iso-propylpiperazine-2,5-dione exhibit high levels of enantiodiscrimination in alkylations with (RS)-1-aryl-1-bromoethanes and (RS)-2-bromoesters, affording substituted diketopiperazines containing two new stereogenic centres in high de. Deprotection and hydrolysis of the resultant substituted diketopiperazines provides a route to the asymmetric synthesis of homochiral methyl 2-amino-3-aryl-butanoates and 3-methyl-aspartates in high de and ee.     

N-α-Benzyloxyacetyl derivatives of (S)-4-benzyl-5,5-dimethyloxazolidin-2-one for the asymmetric synthesis of differentially protected α,β-dihydroxyaldehydes

α-Dibenzylamino- and α-benzyloxy- derivatives of N-acetyl-(S)-4-benzyl-5,5-dimethyloxazolidin-2-one readily undergo highly stereoselective boron mediated syn-aldol reactions with a range of aromatic and aliphatic aldehydes, generating the syn-aldol products in good to excellent yields as single diastereoisomers after purification. In the α-dibenzylamino series, deprotection of the functionalised aldol fragments to the corresponding α-amino-β-hydroxy methyl ester or α-amino-β-hydroxyaldehyde proved problematic, with a range of N- and O-protecting groups giving mixtures of products arising from endocyclic and exocyclic cleavage pathways. However, in the α-benzyloxy series, O-silyl protection of the aldol products, and subsequent DIBAL reduction gives stereoselectively the corresponding N-1′-hydroxyalkyloxazolidin-2-ones, which undergo base promoted fragmentation to the desired highly functionalised and differentially protected α,β-dihydroxyaldehydes in good yields and without loss of stereochemical integrity.     

In vivo monitoring of skeletal aluminum burden in patients with renal failure

In vivo neutron activation analysis was used to examine the total body and partial body (hand) aluminum levels in patients with end-stage renal failure. Patients maintained on chronic hemodialysis had higher mean body burdens of aluminum than, did those clinically managed without dialysis. Approximately 70% of the patients examined indicated elevated levels of body or skeletal aluminum. A significant correlation was observed between the in vivo aluminum/calcium ratio obtained for the hand measurement and the increase in serum aluminum levels following a disferroxamine infusion test. The direct in vivo monitoring of hand Al/Ca values in patients may provide an alternate choice to bone biopsy for the detection of aluminum intoxication.     

SuperQuat 5,5-dimethyl-4-iso-propyloxazolidin-2-one as a mimic of Evans 4-tert-butyloxazolidin-2-one

The incorporation of a gem-dimethyl group at the 5-position of a chiral oxazolidinone biases the conformation of the adjacent C(4)-stereodirecting group such that the gem-dimethyl-4-iso-propyl combination mimics a C(4)-tert-butyl group, providing higher levels of stereocontrol than a simple 4-iso-propyloxazolidinone. The generality of this principle is demonstrated with applications in stereoselective enolate alkylations, kinetic resolutions, Diels-Alder cycloadditions and Pd-catalysed asymmetric acetalisation reactions.     

Discovery of a nuclear isomer in 65Fe with penning trap mass spectrometry

A new long-lived isomeric state in (65)Fe has been discovered with Penning trap mass spectrometry and high-precision mass measurements of the neutron-rich isotopes (63-65)Fe and (64-66)Co have been performed with the Low-Energy Beam and Ion Trap Facility at the NSCL. For the new isomer in (65)Fe an excitation energy of 402(5) keV has been determined from the measured mass difference between the isomeric and ground states. The mass uncertainties of all isotopes have been reduced by a factor of 10-100 compared to previous results. In the case of (64)Co the previous mass value was found to deviate by about 5 standard deviations from the new measurement.     

Precision Penning trap mass measurements of rare isotopes produced by projectile fragmentation

The low-energy beam and ion trap facility LEBIT at NSCL/MSU is at present the only facility where precision experiments are performed with stopped rare isotope beams produced by fast-beam fragmentation. LEBIT combines high-pressure-gas stopping with advanced ion manipulation techniques to provide brilliant low-energy beams. So far these beams have mainly been used for mass measurements on short-lived rare isotopes with a 9.4T Penning trap mass spectrometer. Recent examples include ^70m Br , located at the proton dripline, ³²Si and the iron isotopes ^63-65Fe . While the measurement of ³²Si helps to solve a long-standing dispute over the validity of the isobaric multiplet mass equation (IMME) for the A = 32 , T = 2 multiplet, the mass measurements of ^65m,g Fe marked the first time a nuclear isomeric state has been discovered by Penning trap mass spectrometry.     

Double diastereoselective [3,3]-sigmatropic aza-Claisen rearrangements

Asymmetric [3,3]-sigmatropic aza-Claisen rearrangement of the (Z)-N-allyl-N,O-silylketene aminal of (3S,4E,alphaR)-1-benzyloxy-3-(N-propionyl-N-alpha-methylbenzylamino)hex-4-ene furnishes (2S,3R,4E,alphaR)-N-alpha-methylbenzyl-2,3-dimethyl-7-benzyloxyhept-4-enamide in > 92% d.e.; rearrangement of the diastereomeric (3R,4E,alphaR)-(Z)-N,O-silylketene aminal proceeds with low diastereoselectivity.     

Determination of urinary prostanoids by capillary gas chromatography/high-resolution mass spectrometry

A stable isotope-dilution gas-chromatography/high-resolution mass spectrometry method for the determination of prostaglandin E₂ (PGE₂) and 6-keto-prostaglandin F_1α (6-keto-PGF_1α) in urine as their methoxime/t-butyldimethylsilyl ether/t-butyl-dimethylsilyl ester derivatives is described. The derivatives are prepared by a novel derivatization scheme in which the pentafluorobenzyl esters are formed prior to the silylation step in which the t-butyldimethylsilyl esters are formed in an apparent exchange reaction. Recoveries through the entire extraction and derivatization procedure are 70.6% for PGE₂ and 64.4% for 6-keto-PGF_1α. Quantitation at mass resolutions approaching 10 000 eliminated all interferences in the PGE₂ chromatograms while lower resolutions were sufficient for 6-keto-PGF_1α. Limits of detection of 50 pg ml^?1 for each prostanoid were obtained. For PGE₂, a lower limit of detection was obtained at a mass resolution of 10 000 (50 pg ml^?1) than was obtained at a mass resolution of 1000 (80 pg ml^?1), illustrating the selectivity of detection.     

Asymmetric synthesis of substituted 1-aminocyclopropane-1-carboxylic acids via diketopiperazine methodology

Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N,N'-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-(2)H2]-1-aminocyclopropane-1-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.