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A number of different approaches are being investigated to obtain high-performance mid-infrared (2-5 μm) diode lasers for applications such as infrared lidar, remote sensing and environmental monitoring. They include laser heterostructures based on interband transitions in quantum-well or superlattice active region, and quantum cascade structures based on unipolar intersubband transitions. The Sb-containing structures, employing GaSb, InAs, AlSb and related alloys, are focusing actually much attention. Significant improvements in the molecular beam epitaxy of these alloys make possible now the growth of laser antimonide structures of high structural quality. Excellent performances have been reported at = 2 μm from GaInAsSb /AlGaAsSb and at = 3.5 μm from InAsSb/InAlAsSb type-I quantum-well diode lasers. Type-II (staggered alignment) GaInAsSb/GaSb and type-III (broken gap alignment) InAs/Ga(In)Sb strained multiquantum-well lasers are promising material systems for mid-infrared sources, due to their large conduction and valence band offsets, the potential of Auger process suppression and the enhancement of the electron-hole optical coupling by wave function engineering. Besides high performance interband quantum cascade lasers operating at room temperature with negligible current leakage and high output power can be designed from Sb-containing type-III structures.

Based on information from X-ray, NMR, and SAR data, the N , O -diMeTyr 5 unit of didemnin B was believed to be important for biological activity. To determine the importance of aromaticity and the role of the methoxy group in this unit, two analogs were synthesized in which the N , O -diMeTyr 5 moiety was replaced with N -MeLeu and N -MePhe. Preliminary testing showed that the analogs retained antitumor activity and the ability to inhibit protein biosynthesis in vitro .

Ridge-waveguide laser diodes emitting near 2.38 /spl mu/m have been fabricated from GaInAsSb-GaSb type-II quantum-well (QW) structures grown by molecular beam epitaxy. These devices operated continuous-wave (CW) at room temperature, what is obtained for the first time from a type-II QW laser. At 23/spl deg/C threshold currents in the range 60-140 mA and CW output powers exceeding 1 mW/facet were obtained. These lasers showed a tendency to operate in a single longitudinal mode with a temperature red shift of 0.1 nm//spl deg/C and a current red shift of 0.06 nm/mA.

The astin family of cyclopentapeptides contains several noncoded amino acids, including β-phenylalanine, α-aminobutyric acid and several substituted prolines. The difficult cyclization of the macrocycle and the subsequent first total synthesis of a member of this family, astin G, are discussed herein. This synthesis provides a model for the syntheses of the astins which contain the highly sensitive 3,4-dichloroproline.

A new class of dilute-nitride laser structure to be grown on InAs substrate is simulated for room temperature emission near 3.3 µm. The active region is composed of several strain-compensated type-II InAsN/GaSb/InAsN quantum wells having the “W” geometry so as to maximized the electron and hole wavefunctions overlap. Optical gain calculations at 300 K show high material gain values, of the order of 1000 cm–1 with injected carrier density of 1 × 1012 cm–2. Radiative current density inferior to 100 A/cm2 is predicted for room temperature operation. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

1,2-Indanediones are a new class of fluorogenic reagents for amino acid visualization. In order to better understand the mechanism of formation of the resulting fluorescent products, we have examined the reactions of 1,2-indanediones with amino compounds. Treatment of 1,2-indanedione with 3,5-dimethoxyaniline in benzene afforded several products. The initial mode of addition occurred through attack of nitrogen at the C-2 position of the 1,2-indanedione generating an enamine which underwent subsequent reactions.

A didemnin B analog containing a Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) as a conformationally restrained replacement for tyrosine has been synthesized and shown to have comparable potency as a protein biosynthesis inhibitor. Synthetic highlights include an oxidation of an alcohol to an acid in the presence of the sensitive Tic heterocycle and a modified Schmidt-type one-pot macrocyclization.

The synthesis of roquefortine D (1), an alkaloid isolated from the cultures of Penicillium roqueforti, is described. The absolute stereochemistry of the natural product was determined by comparison of its optical rotation with that of the synthetic product. A photo-cleavable o-nitrobenzyl group was utilized for histidine side chain protection, and the cyclization to the diketopiperazine was carried out under mild conditions.

The naturally occurring cyclopeptide alkaloid sanjoinine G1 and its C-11 epimer were synthesized in 18 steps from D -serine. The key steps in the synthesis were the formation of the alkylaryl ether linkage via an SNAr reaction with 4-fluorobenzonitrile and the macrocyclization to form the 14-membered ring using a modification of the Schmidt protocol involving an activated pentafluorophenyl ester.

A strained 14-membered cyclopeptide was prepared from the Garner aldehyde derived from D-serine. The key steps in the synthesis were the construction of the alkyl-aryl ether linkage via an SNAr reaction involving 4-fluorobenzonitrile and the macrolactamization using a modification of the Schmidt protocol involving an activated pentafluorophenyl ester.

The molecular beam epitaxy growth of strained (Ga, In)Sb/GaSb quantum wells is investigated. In a narrow range of growth conditions, (Ga, In)Sb quantum well structures exhibiting excellent structural properties as well as intense and narrow photoluminescence transitions are obtained. Stimulated emission at 1.98 m is observed at room temperature from laser diodes with strained quantum wells as the active zone. The lasers exhibit threshold current densities as low as 280 A and a characteristic temperature of 75 K.

Efficient syntheses of the esters of cis-3,4-dihydroxyprolines and the first synthesis of the ester of the rare amino acid (−)-(3S,4R)-dichloroproline from trans-4-hydroxy-L-proline are presented. The synthetic route provides easy access to several substituted prolines and cis-hydroxylated proline esters. Various types of biological activities have been associated with these substituted prolines. The role of (−)-(3S,4R)-dichloroproline in astins A, B and C is under investigation.

The syntheses of three modified peptide fragments of the cyclodepsipeptide didemnin B are reported. The HIP and isostatine (1st) units of the didemnin B macrocycle were simplified to a Z-alanine residue and the ester linkage (through threonine of the tetrapeptide) was replaced with amide linkages through the amines of glycine, D-alanine and an ethylenediamine linker. The latter permitted the attachment of a N-Me-D-Leu-Pro-Lac moiety to afford analogs 2, 3 and 4 respectively.

The synthesis of an optically active C, D ring analog of the angiostatic steroid 17-α-hydroxyprogesterone was carried out. © 1997 Elsevier Science Ltd.

β-Hydroxy-λ-amino acids are a class of non-proteinogenic amino acids present in many important biologically active natural products. In conjunction with our research on didemnins, we designed and synthesized a sterically constrained β-hydroxy-λ-amino acid in which the requisite carboxyl, hydroxyl and amino groups are positioned on a conformationally stable 6-membered ring.

Heparin has been recognized as possessing a large variety of cell-modulating activities. Using compositionally simple, structurally rigid, and low molecular weight saccharide molecules (cyclodextrins), we demonstrated that these activities depend primarily on a single, gross compositional parameter: a minimum intramolecular density of neighboring anionic (sulfate) groups. This same critical parameter is shown to be involved in achieving cell-modulating behavior as diverse as angiogenesis, endothelial proliferation, inhibition of smooth muscle cell growth, and cell protection against virus invasion. Physical chemical evidence is presented that associates this property with multi-ionic complex formation between the clusters of anionic and cationic sites on the complexing partners. These observations revive early suggestions of the decisive role of electrostatic complexation capabilities of glycosaminoglycans like heparin; taken together with numerous observations on heparinoids and other agents reported in diverse specialized fields of cell biology and medicine, they provide evidence that molecular agents of critical anionic (sulfate) density (MACADs) represent a broad class of molecules that, in contrast to proteins, do not rely on structural detail for their cell biological activities, but function by ionic complexation with proteinic agents (e.g. growth factors), thereby modifying their structure-specific activities.

As part of investigations directed toward the determination of the essential/nonessential structural features for the bioactivities of didemnin B, we designed a reduced ring analog in which three moieties, namely the tyrosine side chain, the isostatine hydroxyl, and the side chain (l-lactyl-l-prolyl-N-Me-d-leucine), were in their presumed bioactive conformation. In designing the reduced ring analog, we eliminated the leucine-proline portion of the macrocycle core and replaced it with an n-butyl linker in order to elucidate its role. According to MM2 calculations (MacroModel molecular modeling), this analog was of lower energy than the natural product didemnin B, and both structures were superimposable. The synthetic strategy involved four disconnections. Macrocyclization was accomplished at the activated carboxylic acid of the α-(α-hydroxyisovaleryl)propionyl unit (HIP) and the protected amine of the n-butyl linker using a modification of Schmidt's protocol. After selective deprotection of the hydroxyl an...

Magnesium bromide etherate has been previously shown to cleave β-(trimethylsilyl)ethoxymethyl (SEM) esters of aliphatic acids. This methodology has now been extended to amino acid and peptide derivatives in the presence of protecting groups typically encountered in peptide chemistry, including the Boc, Cbz, Fmoc and Troc carbamates as well as benzyl-, tert-butyl- and tert-butyldimethylsilyl ethers. The stability of fluoride sensitive protecting groups to magnesium bromide allows for added selectivity in the removal of SEM esters in organic synthesis.

The synthesis of the previously reported thianinhydrin ( 12 ) was achieved from 3-methylthiophene via the corresponding 5,6-dihydrocyclopenta[ b ]thiophen-4,6-dione ( 10 ). Conversion of 10 to the tricarbonyl ( 12 ) proceeded in good yield using dimethydioxirane oxidation of 5,6-dihydro-5-dimethyl aminomethylenecyclopenta[ b ]thiophen-4,6-dione ( 14 ). The fluorescence intensity of the zinc salt of the product of 12 and glycine was similar to that obtained from the product of ninhydrin and the same amino acid.

Modest to high levels of asymmetric induction are observed with Grignard additions to Garner type aldehydes. The resultant secondary alcohols are important precursors of chiral building blocks for asymmetric synthesis and we have demonstrated that they can be readily converted into their respective γ-hydroxy-β-amino alcohols and β-hydroxyamino acids. Additionally, aryloxy ethers, important components of many natural products, can be obtained from these precursors.

GaSb-based heterostructures with strained-layer (x = 0.26 or x = 0.35) single quantum wells and cladding layers were grown by molecular beam epitaxy. The thickness of the GaInSb well was varied from 3.0 to 14.5 nm. Intense room-temperature electroluminescence was observed from mesa diodes with peak emission wavelengths in the spectral range. The dependence of emission energy on well thickness is consistent with the predictions obtained by an effective mass treatment assuming a rectangular type I quantum well and a conduction band offset .

Although the deprotection of amides by hydrazinolysis is a well established method in carbohydrate chemistry, this reaction is dependent upon the nearby substituents. In our facile synthesis of intermediate benzyl 2-amino-3-azido-4-O-p-methoxybenzyl-6-O-benzyl-2,3-dideoxy-α-d-glucopyranoside (3), we found that the use of trifluoroacetamides provided a more efficient protection strategy.

N-Alkylation of amino acid esters by reductive amination using sodium cyanoborohydride may often be problematic. Sodium triacetoxyborohydride was found to be a convenient reagent for this transformation. This methodology was employed to alkylate various amino acid methyl esters.

Three side chain analogs of didemnin B were synthesized. All three analogs of the only conventional type II β-turn present in didemnin B differed in the functionality incorporated in the threonine residue. The cytotoxic activities of these analogs were evaluated, and one of them exhibited weak activity.

The commercially available α-ketoxime of camphorquinone (1) was reduced to the corresponding exo,exo-amino alcohol (2) in a two-step, one-pot procedure using sodium borohydride and nickel(II) chloride hexahydrate.

A practical and convenient procedure is described for the preparation of gram quantities of (2S, 3S)-3-hydroxyleucine. The key step involves the triflatemediated cyclization of spirooxazolidine 4 to the spirobicyclic compound 5, which is easily converted to the title compound in high yield.

The different reactivities of D-ribonolactone, L-arabinonolactone, D-xylonolactone, D-lyxonolactone 2-deoxy-D-ribonolactone toward benzaldehyde and acetone in acidic media, were examined. The reactions involved complex equilibria and were investigated with extensive 13C NMR studies as well as X-ray crystallographic analysis of selected products. Molecular mechanics (MM2) and semiempirical (PM3 and AM1) calculations of some derivatives were carried out in order to facilitate structural and conformational assignments. The differences in reactivity observed for the reactions of D-pentono-1,4-lactones with benzaldehyde and acetone are rationalized in terms of their structural and conformational features.

Several new 5-arylninhydrins have been prepared using palladium-catalyzed cross-coupling reactions.

The esterification of sterically hindered or non-nucleophilic alcohols may often be problematic. The reaction of alcohols with acid fluorides is reported to be superior to standard acid activation protocols frequently used for difficult esterifications. The acid fluoride methodology was used to produce a hindered linkage between a secondary alcohol (4) and a cyclohexyl amino acid 3, a key intermediate in the formation of a constrained ring didemnin analog.

Two nonessential amino acids, (+)-(S)-2-aminobutanoic acid and the methyl ester of L-β-phenylalanine [(+)- (R)-3-amino-3-phenyl propanoic acid], were synthesized to provide a tripeptide which will be used in the total syntheses of astins A, B, and C.

An asymmetric Diels-Alder reaction in the presence of 3.0 M lithium perchlorate-diethyl ether was used to generate the initial stereochemistry for a cyclohexane amino acid (3), a key intermediate in the preparation of a fused ring didemnin analog. This constrained ring macrocycle should provide insight into the binding site conformation of the bioactive species.

N-Fluorenylmethoxycarbonyl groups may be removed by potassium fluoride/18-crown-6 in the presence of methyl, ethyl, tert-butyl, benzyl, and p-methoxybenzyl esters.

To estimate the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG) in patients under 31 years of age admitted to the emergency department of the University Hospital of Montpellier, for which a urinalysis was performed.CT, NG and MG specific real-time PCRs were performed in the urine samples from 301 patients between July 2010 and January 2011.CT DNA was detected in 11% of patients, NG DNA in 3.7% of patients and MG DNA in one patient. Seventy-five percent of male patients and only 13% of women were diagnosed with sexually transmitted infection (STI). No patient with leucocyturia below 10(4)/mL had a positive PCR result for one of the three bacteria. Of the patients with leucocyturia greater or equal to 10(4)/mL, CT was detected in 23.4% of men and 11% of women, NG in 19.2% of men and 1% of women, and MG in 2.1% of men.The prevalence of NG and CT detection in our population was high while that of MG was low. The diagnosis was facilitated by the use of PCR on the urine sample although this sample is not recommended for the molecular detection of bacterial agents of STIs and may explain the low detection of MG. The study allowed diagnosing STIs in 14.3% of our patient population.

Azabicyclic [3.1.0] and [4.1.0] Kulinkovich products underwent a facile reduction/fragmentation to afford a variety of 3-piperidinones and 3-azepinones, respectively, in the presence of catalytic palladium on carbon and formic acid in an atmosphere of hydrogen.

Enzymes involved in the mammalian microsomal metabolism of drugs are, in numerous cases, inhibited by compounds bearing an imidazolyl scaffold. However, the inhibition potency is highly dependent upon the accessibility of the imidazolyl nitrogen lone pair. In order to highlight some structural parameters of inhibitors that control this phenomenon, a series of compounds containing a nitrogen unsubstituted imidazolyl moiety with varying degrees of nitrogen lone pair accessibility was tested on human and rat hepatic cytochromes P450 and microperoxidase 8, an enzymatically active peptide derived from cytochrome c. In each case, we have shown that the accessibility of the imidazole lone pair determined the extent of inhibition. Nitrogen accessibility was tuned not only by varying the steric hindrance in the vicinity of the imidazolyl ring but also by modifying its surrounding hydrogen bonding network. Compounds in which there exists intramolecular hydrogen bonding between the imidazole moiety and an H-bond acceptor, such as an appropriately positioned amide carbonyl group, demonstrated enhanced inhibitory effects. Conversely, imidazole moieties which are in proximity to H-bond donors, such as an amide NH group, displayed reduced potency. This trend was observed in cyclo-peptide derivatives in which the intramolecular H-bond network was adjusted through the modification of the stereochemistry of a dehydrohistidine residue. It was observed that (Z)-isomers weakly bind heme, whereas (E)-isomers demonstrated higher degrees of metal binding. Therefore, enzymatic inhibition of heme-containing proteins by compounds bearing a dehydrohistidine motif seems to be closely related to its stereochemistry and hydrogen binding propensity. At neutral pH, these differences in binding affinities can be confidently attributed to the ambident H-bond properties of imidazole nitrogen atoms. This structure-activity relationship may be of use for the design of novel imidazolyl compounds as new P450 inhibitors or drug candidates.

Azabicyclic [3.1.0] and [4.1.0] Kulinkovich products underwent a facile reduction/fragmentation to afford a variety of 3-piperidinones and 3-azepinones, respectively, in the presence of catalytic palladium on carbon and formic acid in an atmosphere of hydrogen.

We report on spontaneous and simulated emission from strained InAs quantum wells (QWs) embedded in an Al x Ga 0.48 − x In 0.52 As matrix grown on InP substrates by solid-source molecular-beam epitaxy. By adjusting the QW width between 2 and 23 monolayers and/or the barrier composition between Al 0.48 In 0.52 As and Ga 0.47 In 0.53 As, the low temperature photoluminescence can be tuned between 1.0 μm and 2.2 μm. Efficient room temperature luminescence is achieved up to 2.4 μm which is the longest wavelength reported for QWs grown on InP substrates. Finally, we demonstrate the first stimulated emission near 1.3 μm and 1.8 μm at 80 K in this materials system. These results thus enlarge the wavelength range of applications achievable with InP-based materials.

Twelve selected carboxyl activating reagents have been tested in the β-carbon homologation of D-serine. FDPP and BOP-Cl were the most successful reagents.

The critical thickness of strained AlxGa1−xAsySb1−y layers (0.35 ⩽ x ⩽ 0.58) grown by liquid phase epitaxy (LPE) on GaSb (001) oriented substrates was determined by X-ray double-crystal diffractometry on (115) reflection planes. This method allows one to determine the relative lattice-mismatch perpendicular to the growth direction ( Δa a ) τ and in the junction plane ( Δa a ) ∥ . The state of the epitaxial layer (strained or relaxed) was deduced for mismatches ( Δa a ) 0 = (a AlGaAsSb − a GaSb ) a GaSb varying from −1 × 10−3 to 4 × 10−3. The evaluated critical thickness of layers under tension was: h c (μm) ≈ 0.4 × 10 −3 ( Δa a ) 0 much lower than that of layer under compression: h c (μm) ≈ 2.2 × 10 −3 ( Δa a ) 0 .

A comparative study of the effectiveness of selected coupling reagents in dipeptide synthesis was conducted. Included in the study were a new coupling reagent, pentafluorophenyl diphenylphosphinate (FDPP, 1), benzotriazol-1-yl-oxytris(dimethylamino) phosphonium hexafluorophosphate (BOP, 2), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU, 3), and isobutyl chloroformate (IBCF, 4). We found that BOP (2) afforded the highest yields and lowest limits of racemization.

The detoxin complex, metabolites produced by Streptomyces caespitosus var. detoxicus 7072 GC1, is a selective antagonist of the antibiotic blasticidin S. Two approaches toward the total synthesis of (+)-valyldetoxinine and (−)-detoxin D1 are described. These routes involve a 2,3-disubstituted pyrrolidine as a common intermediate and utilize glucose as the chiral precursor.

The reactions of D-ribono-1,4-lactone, and 2-deoxy-D-ribono-1,4-lactone with benzaldehyde and acetone in acidic media were investigated. The products obtained were isolated and characterized. The 1H NMR spectra of the 1,5-lactone product resulting from the thermodynamically controlled reaction of D-ribono-1,4-lactone with benzaldehyde were examined between 300 °K and 200 °K in a polar solvent. No conformational changes in the 1,5-lactone ring were observed within this temperature range. Detailed NMR studies showed that the acetalization of D-ribono-1,4-lactone proceeded with the initial formation of the endo-2,3-acetal derivative, which in the presence of aqueous acids underwent ring expansion and isomerization to the 3,4-acetal of the 1,5-lactone. The endo preference of benzylidene acetals was explained by the transition state conformation of the reactants and the thermodynamic stability of the products, as calculated with molecular mechanics.

The synthesis of Lys(3) tamandarin M is described. This analogue can be used as a protein affinity ligand to probe the mechanism of action of this unique class of molecules.

Didemnins A, B, and C were efficiently prepared in a stereocontrolled manner, producing the common macrocycle and, in a separate step, introducing the substituents on the amino group of L-threonine as optically pure units. We envisaged that disconnections between L-leucine and the HIP group (2S,4S) and between L-threonine and isostatine (3S,4R,5S) would afford two units: a HIP-isostatine unit (I) and a tetrapeptide unit (II)