Tetrahedron Asymmetry

Published by Elsevier
New 5,6-dihydro-1,10-phenanthroline derivatives were prepared in high yield via ytterbium(III) triflate-catalyzed alcoholysis of the corresponding epoxide. Enzymatic transesterifications of racemic alkoxy alcohols afforded enantioselective separations with up to 99% ee. The lipase derived from Burkholderia cepacia (PSCI) was the most efficient, with E-values of up to 200. The steric effect of substituents in the 6-position on reaction time and enantioselectivities was assessed.
Cyclisation by double reductive amination of 2-acetamino-2-deoxy-D-xylo-hexos-5-ulose with N-2 protected L-lysine derivatives provided 2-acetamino-1,2-dideoxynojirimycin derivatives without any observable epimer formation at C-5. Modifications on the lysine moiety gave access to lipophilic derivatives that exhibited improved hexosaminidase inhibitory activities.
A chemoenzymatic strategy for the synthesis of enantiomerically pure novel alkaloids (1S,3R)-1-benzyl-2,3-dimethyl-1,2,3,4-tetrahydroisoquinolines is presented. The key steps are the biocatalytic stereoselective reductive amination of substituted 1-phenylpropan-2-one derivatives to yield chiral amines employing microbial ω-transaminases, and the diastereoselective reduction of a Bischler–Napieralski imine intermediate by catalytic hydrogenation in the presence of palladium on charcoal, leading exclusively to the desired cis-isomer.
Triple monoamine reuptake inhibitors have been implicated in the development of a new generation of antidepressants with higher efficacy than the currently existing therapies. In this paper, we have developed an alternative efficient synthetic route for triple monoamine reuptake inhibitor D-142 in 18.5% overall yield in 11 steps starting from diphenylmethane. D-142 was developed by us recently. The key step of the present synthetic strategy is the preferential formation of a bromohydrin from olefin via a cis-bromoinum intermediate, which introduced significant efficiency in the overall synthesis. Furthermore, we have developed an efficient way to recycle the optically active intermediate diol back to the desired chiral epoxide.
All 4 diastereomeric possibilities for the 2,3-dihydroxy-2,6,8-trimethyldeca-(4Z,6E)-dienoic acid (Dhtda) residue, found in the cyclic depsipeptide natural products papuamides A-D and mirabamides A-D, were stereoselectively synthesized using a Z-selective Wittig reaction of both enantiomers of 2,4-dimethylhex-2-enyl-triphenylphosphonium bromide with all four diastereoisomers of ethyl-3-formyl-2-methyl-1,4-dioxaspiro[4,4]nonane-2-carboxylate. To elucidate the configuration of Dhtda, the (1)H- and (13)C-NMR spectra of the synthetic isomers were compared to those of the natural residue. On the basis of that comparison, it is suggested that the likely configuration of the diastereomer present in Dhtda residue is either (2R,3S,8S) or (2S,3R,8S) in the papuamides and mirabimides.
The enantioselective synthesis of the (R,R)- and (S,S)-enantiomers of 1 from commercially available 3-chlorocinnamic acid is reported. The Sharpless asymmetric epoxidation was used to establish the stereocenters in the synthesis of both enantiomers of 1.
A high yielding and remarkably stereoselective alpha-methylation reaction of the (2S,3aS,7aS) stereoisomer of octahydroindole-2-carboxylic acid, (S,S,S)-Oic, suitably protected is described. The severe steric hindrance imposed by the fused cyclohexane ring, which prevents the application of Seebach's self-reproduction of chirality methodology, accounts for the formation of (S,S,S)-(alphaMe)Oic with high selectivity and retention of configuration.
The ability of commercially available amino acid derivatives, especially Fmoc-Trp(Boc)-OH, to differentiate enantiomers of chiral phosphonates, phosphinates, phosphates, phosphine oxides, and phosphonamidates is demonstrated with (31)P, (13)C, and (1)H NMR spectroscopy. The chiral differentiation provided a rapid and convenient method for measuring the enantiomeric purity of these phosphorus compounds.
The organocatalytic enantioselective tandem aldol-cyclization reactions of α-isothiocyanato imides and activated carbonyl compounds, such as isatins, an α-ketolactone and a 1,2-dione, have been studied with cinchona alkaloid-derived thiourea-catalysts. This methodology provided an easy way to access enantiomerically enriched spirobicyclic thiocarbamates with high yields and good to excellent stereoselectivity, which have been demonstrated to be useful precursors for the synthesis of biologically active molecules.
The most recent papers describing the stereoselective synthesis of cyclic quaternary alpha-amino acids are collected in this review. The diverse synthetic approaches are classified according to the size of the ring and taking into account the bond that is formed to complete the quaternary skeleton.
Asymmetric multi-component reactions of optically active phenyl dihydrofuran, keto ester or N-tosyl imino ester, and allylsilane provided functionalized phenyl tetrahydrofurans with multiple stereogenic centers diastereoselectively. Cleavage of the resulting substituted tetrahydrofurans readily provided acyclic derivatives with three contiguous asymmetric centers via an acyloxycarbenium ion intermediate. Ring closing olefin metathesis, using Grubbs catalyst, afforded functionalized cyclopentene derivatives in optically active form. A one pot tandem tetrahydrofuran ring cleavage followed by ring closing olefin metathesis also provided functionalized cyclopentenes in good yield.
A series of alpha-amino acid derivatives containing the 2,3-dihydroindole or octahydroindole core have been chemoenzymatically synthesized in good overall yields and high enantiomeric purity under mild reaction conditions using lipases for the introduction of chirality. Candida antarctica lipase type A has shown excellent activity and high enantiodiscrimination ability towards the two cyclic amino esters used as substrates. The selectivity of the process proved to be greatly dependent on the alkoxycarbonylating agent. Thus, the enzymatic kinetic resolution of methyl indoline-2-carboxylate has been successfully achieved using 3-methoxyphenyl allyl carbonate, whereas (2R,3aR,7aR)-benzyl octahydroindole-2-carboxylate required the less reactive diallyl carbonate.
We have investigated the effect of nitrogen protecting groups in radical addition trapping experiments leading to beta(2)-amino acids. Of the three N-protecting groups examined, the phthalimido group was optimal with respect to both yields and enantioselectivity. Additionally, radical additions to more complex acrylates were also investigated, which provided access to functionalized beta(2)-amino acids in modest selectivity.
Chiral spiroborates derived from non-racemic 1,2-aminoalcohols.
Amount of catalyst 1 versus % ee of 1-(3-pyridyl)ethanol.
The effectiveness of several spiroborate ester catalysts was investigated in the asymmetric borane reduction of 2-, 3-, 4-acetylpyridines under different reaction conditions. Highly enantiomerically enriched 1-(2-, 3- and 4-pyridyl)ethanols and 1-(heterocyclic)ethanols were obtained using 1 to 10% catalytic loads of the spiroborate 5 derived from diphenylprolinol and ethylene glycol.
The transmetallation of lithium alkoxides and enolates with a copper(I) halide salt provides the requisite nucleophiles to accomplish the stereospecific rhodium-catalyzed allylic substitution. These studies demonstrate that the nature of the halide ion derived from the copper(I) salt has a profound effect on regioselectivity and enantiospecificity. This observation was attributed to the trans-effect, by virtue of an in situ modification of the catalyst by the halide ion, which leads to modulated catalytic activity and improved stereospecificity.
Various substituted arylcuprates undergo stereocontrolled additions to L-serine-derived γamino- and γ-carbamato-α,β-enoates with high syn-selectivities. The stereochemical outcome of these reactions is fully consistent with the reductive elimination-based model proposed previously. This method is well suited for the preparation of a broad range of biologically active amaryllidaceae constituents and their aromatic analogues.
Polymer-supported chiral amines were effectively prepared from amino acid derivatives and Merrifield resin. Treatment of polymer-supported amines with n-butyllithium gave the corresponding polymer-suppported chiral lithium amide bases, which were tested in the asymmetric deprotonation reactions of prochiral ketones. The trimethylsilyl enol ethers were obtained in up to 82% ee at room temperature. The polymer-supported chiral lithium amides can be readily recycled and reused without any significant loss of reactivity or selectivity.
A new fluorous 2-chloropyridinium hexafluorophosphate was prepared as a modified Mukaiyama condensation reagent, and it was applied in amide formation reactions. Good to excellent purities of amides were obtained after fluorous solid-phase extraction of reaction mixtures without additional chromatography.
Epoxy quinol 1a was prepared on a multi-gram scale by Noyori transfer hydrogenative desymmetrization of the readily available meso epoxy diketone 4. Although the intrinsic enantioselectivity for the desymmetrization was modest (82:18 er at 4% conversion), a highly enantiopure product (99.6:0.4 er) could be obtained in one operation in 44% yield via kinetic resolution of the minor enantiomer with long reaction times (48 h), or in 73% yield by combination with an enzymatic resolution of a 93:7 er mixture.
Herein we describe an asymmetric approach to the synthesis of a BC-ring synthon in tuberostemoninol via an intramolecular Pauson-Khand reaction stereocontrolled by a commercially available chiral glycinate.
Prochiral heteroaryl ketones containing furan, thiophene, chroman and thiochroman moieties were successfully reduced in the presence of 1 - 10 mol % of spiroaminoborate ester 1 with different borane sources to afford non-racemic alcohols in up to 99% ee. In addition, modest enantioselectivity, around 80% ee, was achieved in the reduction of linear α,β-unsaturated heteroaryl ketones.
O-TBS-protected methyl trans-4-hydroxypyroglutamate and methyl trans-4-hydroxyproline ester were synthesized from nitroso-cyclopentadiene Diels-Alder cycloadducts. Enzymatic resolution of the key intermediate, 4-amino-cyclopent-2-enol, provides access to both L- and D- amino acids.
The asymmetric organocatalytic alpha-sulfenylation of substituted piperazine-2,5-diones is reported, with cinchona alkaloids as chiral Lewis bases and electrophilic sulfur transfer reagents. Catalyst loadings, the type of sulfur transfer reagent, temperature and solvent were investigated in order to optimize the reaction conditions. The effects of ring substitution and the type of catalyst on the yield and enantioselectivity of the reaction are reported.
A range of glycopeptides containing protease cleavage sites were synthesized on solid support using Fmoc-based solid phase glycopeptide synthesis. The immobilized peptides were studied as substrates for the proteases chymotrypsin and thermolysin. For chymotrypsin, N-glycosylation of an Asn residue at the P(2) site appears to reduce hydrolysis whereas glycosylation of the P(1) site does not appear to affect peptide hydrolysis by thermolysin.
A short synthesis of the enantiomer of the polyacetylenic natural product siphonodiol is described. The synthesis is based on the strategy of taking advantage of the hidden symmetry of the target molecule and minimizing the use of protecting groups, thereby reducing the total number of steps and increasing the overall efficiency.
A monolithic receiver chip architecture and its simulation methodology for SONET (Synchronous Optical Network) OC-3 application are described. AGC (Automatic Gain Control) amplifier, timing recovery, and decision circuits will be incorporated in one chip by using a single 5-V power supply double-poly-double-metal 1.0-μm BiCMOS technology. A mixed-mode simulation approach for Workview and Hspice is applied for the whole chip simulations
The authors analyze the serial and parallem implementation of a SONET STS-3c based asynchronous transfer mode (ATM) user network interface design. The tradeoffs between both serial and parallel desings of the SONET scrambler and the ATM physical layer cyclic redundancy code (CRC) generator are analyzed in terms of gate count and power dissipation. The result of the analysis shows that an 8-b parallel processing of the ATM header CRC and the SONET scrambler offers the optimal solution in terms of performance and cost of implementation
The adequacy of the measurement methodology of the three antenna method of ANSI Standard C63.5 is addressed. The transmit receive pairing of the three antennas, as required in the standard, where one of the antennas is not used to transmit, has been challenged as not providing the most accurate answers. Instead, an alternative pairing has been proposed where all three antennas both transmit and receive. The authors describe a series of measurements that addresses the difference in the standard and proposed measurement methodologies, and determines if a change is needed in the measurement standard. It is found that the measurement methodology of ANSI 63.5 and the measurement methodology proposed as an alternative, where each antenna is used for both transmission and reception, provide virtually identical results. It is concluded that no changes in the methodology of the ANSI standard three antenna method of measuring antenna factors are required
A six-chambered vapor diffusion apparatus is currently used for protein crystal growth experiments in microgravity environments on board the Space Shuttle. Temperature is a thermodynamic variable that dictates the solubility of solutions. The objective is to employ the temperature parameter so as to devise an apparatus that can control the temperature of the protein solution. This will allow a condition of saturation to be approached in a careful and predetermined manner. This approach is expected to form fewer nucleation sites for the protein crystals, thereby resulting in the production of fewer, larger crystals of superior quality. Implementation of this methodology, from the control of the dynamic variable temperature to the effective design of the VDA for accurate temperature measurement and control, taking into consideration the power constraints available on board the Space Shuttle, forms the focal point of this project
Existing fault simulation techniques have a worst-case computational complexity of O(n**2), where n is the number of devices in the circuit. A parallel hardware accelerated fault simulator (PHAFS) has been proposed in order to reduce the complexity to O(L**2), where L is the number of levels of switches encountered when traversing from output to input. An overview of the PHAFS architecture and system is presented. The PHAFS hardware component uses a massively parallel SIMD (single instruction, multiple data) architecture based on an application specific integrated circuit to perform two-dimensional parallel switch level fault simulation up to 32 switches and 192 faults
A DS/CDMA (direct-sequence code division multiple access) system using BPSK (binary phase shift keying) modulation is simulated to determine the bit error probabilities for various numbers of users with a processing gain close to that of a cellular network. The results are compared to results obtained using the Gaussian approximation equations. The results obtained are to the feasibility of a DS/CDMA cellular network. It is concluded that DS/CDMA cellular networks appear to offer higher subscriber capacities than existing analog or TDMA (time division multiple access) formats. In addition, DS/CDMA offers additional advantages such as inherent privacy through the use of spreading codes and the ability to combat problems such as multipath fading and narrowband noise
Many segments of the video/imaging industry have intensified the demand for image resizing capabilities. Systems developers generally cannot afford to invest millions of dollars in DSP research and development. If a standard image resizing IC core technology can be assessed and embedded within the system specification, highly integrated, high quality low-cost ASIC solutions can be realized. The authors present the fundamentals of digital image resizing, introduce the Genesis ACUITY technology, and describe the design and development methodology for image resizing ASICs using ACUITY cores
The authors describe the most appropriate I/O (input/output) interface schemes for representative microprocessors. They also present some typical applications such as control timing generation, feedback control system, data coding, and display applications. They use the most popular 16/32 bit microprocessors such as the Intel 8086 and Motorola 68000 families in their case studies
A menu-driven free-space optical interconnect simulation program is described which affords prospective users the ability to evaluate and characterize the performance of an interconnect design prior to proceeding with a hardware realization. The simulation consists of discrete device models, whose parameters can be modified at the user's discretion by selecting the desired model option and editing the appropriate parameter setting. Multiple quantum well laser diode and positive intrinsic negative (PIN) photodiode device models, derived from theoretical prescriptions, are used to simulate the characteristic behavior of the transmit and receive planes. Hardware-dependent error source models have been developed which can be used to observe their associated effects on overall system-level performance. The simulation described here characterizes the performance of a proposed interconnection network in terms of performance metrics which include throughput, signal-to-noise ratio and bit-error rate
A typical phased development approach to CASE (computer-aided software engineering) is discussed. The methodologies that define the unit subsystems matrices are all contained in one all-encompassing methodological set that is referred to as USE, or (Unified Systems Engineering). CASE, with the USE methodology, meets the need to specify the system design in objective, rational, and state-of-technology objectives. USE is a mathematical modeling methodology which includes electrical, inertial, fluidic, structural, and thermal conduction submethodologies
The Phillips Laboratory has recently designed and constructed a CW (continuous wave), low-level simulator (ELLIPTICUS) for use in determining coupling of electromagnetic energy to aerospace systems. The antenna is loaded with ferrite beads which have resistors wrapped around them so that a relatively constant resistive load is achieved over a large frequency band. The number of ferrites on the antenna is determined to make the field patterns similar to those produced at the high level pulse simulator, HPD. The HPD simulator with the HAG II pulser was used to measure responses of the same test points on the EMPTAC aircraft which were measured with the CW simulator. How well the responses in the low level CW and high level pulse simulators compare when normalized to similar incident field strengths has been examined
Parallel operation of Brayton cycle alternators with automatic voltage and active power control is considered. An implementation and application of that theory are used to develop algorithms for system analysis in various test cases. A single machine algorithm with control is developed first. Multimachine parallel operation of the alternators, based on the single machine algorithm, is then developed. Finally, an algorithm for the complex system which includes various groups of the Brayton cycle alternators operating in parallel with network and loads is developed. Smooth control of the alternators in parallel operation sharing the generation of the power among the alternators illustrates the feasibility of the proposed control concept
The author introduces a parallel structure termed a message-based systolic attached processor (MSAP) for the efficient implementation of matrix product algorithms. The architecture consists of a set of systolic nodes of fixed size and dimension connected by a global network, called the system interconnection network. The systolic nodes have their own local memory and can access a common global one. Communication protocols among the nodes are message-based and are similar to the ones used in the n-cube. The new architecture represents a family of algorithm-specific structures that can be custom-designed to solve a particular problem more efficiently. The author also describes a graph-theoretic technique for expressing the evolution of partial results in the structure as a function of the compute cycles in the form of a timing graph. Appropriate procedures for analyzing the timing graph are introduced. Analysis of the timing graph allows the modification of the array operation so that it could implement structured sparse matrix multiplication in reduced time
A feasible auto-tuning method for DC brushless servo systems that introduces fuzzy algorithms is described. This is basically considered as a technique to adjust two gains of a proportional-integral (PI) compensator under the principle of providing an additional reference generator, observer, and fuzzy inferencer with a general-purpose speed control loop including PI regulator. It is possible to adjust the gains so as to be an optimum level through repeating 10 responses or more step responses in relation to variations of load inertia and mechanical vibration in addition to control characteristic fluctuations. It is proved that a DC brushless servo system can be automatically tuned to provide an optimum response if it is in a completely unstable state on the basis of the experimental results
The development of dynamic power system models for space applications which use multiple generators operating in parallel is presented. The system will include a mathematical model of the Brayton cycle alternator with voltage and active power control in both single operation and a multiple generator in parallel operation. Multiple generators operating in parallel at the same bus and connected to the system network each have a single parasitic load speed control. Coordination of the control actions of a single alternator and a group of alternators sharing the common system load demand is formulated, and mathematical models and control are developed. The more general case of complex system control and coordination of control actions with the parasitic load controllers is presented, and the mathematical model is formulated. The subject of the parallel operation of Brayton cycle alternators is treated from the point of view of system formulation and mathematical model definition
The Minitaur-II parallel processor computer has been developed for real-time processing of audio signals. It consists of nine TMS 320C30 processors distributed over three 9U VME boards which are installed in a SUN workstation. The shared memory system of the Minitaur-II has a number of novel capabilities including the ability to create a segmented bus in real-time, initiate indivisible transfers of large data structures, broadcast data to multiple processors, and dynamically allocate data among the processors. The architectural capabilities of the Minitaur-II system have been duplicated in a set of SUN library functions, so that users may debug multiprocess programs on a single workstation, and then recompile and down-load them to the parallel processor
A compiler for the language Joyce, creating code for the Intel iPSC/2 hypercube, is described. A specialized intermediate language, the spawning stack machine, is used to allow efficient translation to the parallel target machine. This intermediate language is an architecture-independent description of parallel or distributed computation, and should prove useful in construction of portable compilers for many types of parallel computers
The author presents a procedure for synthesizing an MOS circuit with an approximately exponential voltage-current characteristic. Analysis of an infinite array of ideal MOSFETs yields mathematically convenient results, which guide the development of an algorithm for finite arrays of nonideal MOSFETs. Given a desired exponential function, the design algorithm determines the required MOSFET device sizes
The need for a transient fault recovery procedure in a wavefront processor array is examined. The idea of data rollback to recover from transient faults is considered. Data rollback is achieved by creating checkpoints at different instants of time; when an error occurs, backtracking is done to a consistent state and computation resumes from that state. An algorithm for data rollback in wavefront processor arrays is developed. After the fault is detected, the error information is propagated throughout the array. A distributed recovery algorithm is employed, so that there is no single point of failure in the fault recovery mechanism. An important criterion in the data-rollback algorithm is that the processing elements are designed to be totally self checking; this ensures that there is no rollback propagation
A device designed for clock extraction in an ATM optical network for a fiber in the loop system operating at 155/622 Mb/s is presented. The device applies a new clock phase alignment technique to recover the clock/data signal from up to 16 remote nodes
With the advent of high performance technologies (sub-micron CMOS, BiCMOS, and BiNMOS), the practicality of automated test data development will be emphasized. Although automatic test pattern generation and timing analysis are currently considered desirable, the complexity and size of future ICs will make them mandatory. The author describes a new trend in test data development for a complex semi-custom IC and the benefits of that methodology through the development of an ASSP (application specific standard product)
The authors study the representation of the speech waveform using a basis set or kernel function derived from Bessel functions of the first kind. These functions have regular zero-crossings but decaying amplitudes that provide a better match to the behavior of speech waveforms. In addition to exploitation of such improved efficiency for storage and compression systems, the authors have shown the possibility of improving signal-to-noise ratio by filtering which attenuates more of the noise power without attenuating the desired signal. Ideal specifications of signal and additive noise spectra and the ideal amplitude characteristic of a low-pass filter are used to illustrate the possible improvement of signal-to-noise ratio. Then, the improvement in convergence rate of the Fourier-Bessel transform is illustrated by comparing the Fourier and Fourier-Bessel transforms of a set of signals which become more speech-like. Simulation results showing the improvement in a signal-to-noise ratio of speech segments are presented
High-speed heterojunction bipolar transistors (HBTs) in the InP/InGaAs material system have been monolithically integrated with p-i-n photodetecters as receivers and with quantum well lasers as transmitters for potential applications in long wavelength lightwave communications. Speeds well beyond 5 Gb/s have been achieved with excellent performance
A custom DSP chip for mobile radio systems like the American IS-54 system is presented. The application is a digital intermediate frequency filter which is intended to replace expensive analog filters. It is a lattice wave digital filter with fixed coefficient bit-serial arithmetic. A technique which is useful for area efficient layouts in high throughput real time signal processing is discussed
The authors study some of the properties of the parametric representation of a cube of a Boolean function reported by D. Lee et al. (1987, 1988). This representation describes a cube in terms of its origin, which represents the smallest of the integers representing the minterms in the cube and the logarithmic distance between the origin and the minterms in the cube that are adjacent to it. These distances are called parameters of the cube. Using this parametric representation, two algorithms are developed to obtain fast reduction of a specified Boolean function with a large number of variables. A comparison of these algorithms is made with the existing algorithms for minimization from different points of view
Top-cited authors
Carmen Najera
  • University of Alicante
Albert S. C. Chan
  • Hong Kong Baptist University
George Fleet
  • University of Oxford
Vicente Gotor
  • University of Oviedo
Ferenc Fulop
  • University of Szeged