Diverse modes of reactivity of dialkyl azodicarboxylates with P(III) compounds: synthesis, structure, and reactivity of products other than the Morrison-Brunn-Huisgen intermediate in a Mitsunobu-type reaction

The reactivity of diethyl azodicarboxylate (DEAD)/diisopropyl azodicarboxylate (DIAD) with P(III) compounds bearing oxygen or nitrogen substituents is explored. Compounds with structures quite different from that of Morrison-Brunn-Huisgen intermediate R'(3)P(+)N(CO(2)R)N(-)(CO(2)R) (1), observed in the Mitsunobu reaction, have been established by using X-ray crystallography and NMR spectroscopy. Thus reactions with X(6-t-Bu-4-Me-C(6)H(2)O)(2)P-NH-t-Bu [X = S (8), CH(2) (9)] or XP(mu-N-t-Bu)(2)P-NH-t-Bu [X = Cl (14) or NH-t-Bu (15)] and DEAD/DIAD lead to phosphinimine-carbamate-type of products X[6-t-Bu-4-Me-C(6)H(2)O](2)P[N-t-Bu][N(CO(2)R)NH(CO(2)R)] [X = S, R = Et (16); X = CH(2), R = Et (17); X = CH(2), R = i-Pr (18)] or XP(mu-N-t-Bu)(2)P(N-t-Bu)[N-(CO(2)-i-Pr)-N(H)(CO(2)-i-Pr) [X = Cl (19), NH-t-Bu (20)]. Treatment of 19 with 2,2,2-trifluoroethanol afforded the product [(CF(3)CH(2)O)P(mu-N-t-Bu)(2)P(+)(NH-t-Bu)[N(CO(2)-i-Pr)(HNCO(2)-i-Pr)]][Cl(-)] (21) whose structure is close to one of the intermediates proposed in the Mitsunobu reaction. The isocyanate CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P-NCO (10) underwent 1,3-(P,C) cycloaddition with DEAD/DIAD to lead to CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P[N(CO(2)R)N(CO(2)R)-C(O)-N] [R = Et (22), i-Pr (23)]. Reaction of 22-23 with 1,1'-bi-2-naphthol or catechol leads to novel tetracoordinate CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P(2,2'-OC(10)H(6)-C(10)H(6)-OH)[NC(O)-(CO(2)R)NH(CO(2)R)] [R = Et (24), i-Pr (25)] or pentacoordinate CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P(1,2-O(2)C(6)H(4))[NHC(O)-N(CO(2)R)NH(CO(2)R)] [R = Et (26), i-Pr (27)] compounds in which the original NCO residue is retained; this mode of reactivity is quite different from that observed for the MBH betaine 1. In 27, the nitrogen, rather than the oxygen, occupies an apical position of the trigonal bipyramidal phosphorus violating the commonly assumed preference rules for apicophilicity. It is shown that the previously reported azide derivative 3, obtained from the reaction of 11 with DIAD, undergoes a Curtius-type rearrangement to lead to the fused cyclodiphosphazane [(CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2))P(OC(O-i-Pr)NN(CO(2)-i-Pr)N)](2) (28); this compound is in equilibrium with its monomeric form in solution at >300 K. Finally, reaction of S(6-t-Bu-4-Me-C(6)H(2)O)(2)P(OPh) (13) with DIAD gave the hexacoordinate compound S[6-t-Bu-4-Me-C(6)H(2)O](2)P(OPh)[N(CO(2)-i-Pr)NC(O-i-Pr)O] (30) with an intramolecular S-->P bond. X-ray crystallographic evidence for compounds 16, 19, 21, 22, 25, 27, 28, and 30 has been provided.     

Apical versus equatorial disposition of substituents in tetraoxyphosphoranes bearing a 1,3,2-dioxaphosphocin ring: implications on apicophilicity in trigonal bipyramidal phosphorus

New spirocyclic (amino/amido)tetraoxyphosphoranes CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P(NRR')(O(2)C(6)Cl(4)) [R = Me, R' = Ph (1), R = R' = i-Pr (2); R = R' = H (3); R = H, R' = Ph (4)] and the isothiocyanatotetraoxyphosphorane CH(2)(6-t-Bu-4-Me-C(6)H(2)O)(2)P(NCS)(O(2)C(6)Cl(4)) (5) have been synthesized. X-ray crystallography for these compounds reveals that -N(Me)Ph, -N(i-Pr)(2), and -NCS groups occupy an apical position whereas -NH(2) and -NHPh groups occupy an equatorial position in a trigonal bipyramidal geometry around phosphorus. These results are in contrast with the common assumption that a sterically bulky and less electronegative substituent [e.g. -N(i-Pr)(2)] should be less apicophilic than a sterically small and more electronegative substituent (e.g. -NH(2)). The possible rationalization for these results is discussed. Variable-temperature ((1)H, (31)P) NMR spectra of these compounds show some unusual features not reported before for pentacoordinate phosphorus. Probable intramolecular processes involving (i) apical-equatorial <--> equatorial-apical exchange, (ii) apical-equatorial <--> equatorial-equatorial exchange, and (iii) boat-chair <--> tub (for the eight-membered ring) interconversion as well as cessation of the P-N bond rotation have been invoked to explain the spectral features.     

Evidence of enhanced reactivity of DAAP nucleophiles toward dephosphorylation and deacylation reactions in cationic gemini micellar media

4,4'-(Dialkylamino)pyridine (DAAP)-based compounds 1-4 catalytically cleave hydrophobic organophosphate and carboxylate esters in various host micellar aggregates at mildly alkaline pH. The role of the micellar reaction medium in such esterolytic reactions has been carefully examined in this work. The cationic gemini surfactant based micellar aggregates provide more than 1 order of magnitude better reaction medium for the above reactions than their conventional single-chain, single-charge, cationic cetyl trimethylammonium bromide (CTABr) micelles. The catalytic turnover behavior of DAAP nucleophiles in the presence of excess substrates is also retained in gemini micellar media.     

Raman-activated cell counting for profiling carbon dioxide fixing microorganisms

Raman microspectroscopy is a label-free and nondestructive technique to measure the intrinsic chemical profile of single cells. The naturally weak Raman signals hampered the application of Raman spectroscopy for high-throughput measurements. Nearly all photosynthetic microorganisms contain carotenoids that are active molecules for resonance Raman at a 532 nm excitation wavelength. Hence, the acquisition time for a single photosynthetic microorganism can be as short as 1 ms. The carotenoid bands in Raman spectra of photosynthetic microorganisms utilizing (13)CO(2) shifted when compared to the spectra of cells utilizing (12)CO(2). Here, a mixture of (12)C- and (13)C-cyanobacterial cells were counted using a microfluidic-device-based Raman-activated cell counting procedure to prove the concept that Raman spectroscopy can be used as a high-throughput method to profile a cell population.     

Novel benzopyranopyridine derivatives of 2-amino-3-formylchromone

Enol lactones such as 4-hydroxy-6-methyl-2H-pyran-2-one (triacetic acid lactone, TAL) and 4-hydroxycoumarin when treated with 2-amino-3-formylchromone under basic conditions afforded 3-acetoacetyl benzopyranopyridones and benzopyranopyridines, respectively. A series of pyrazole derivatives was prepared by the reaction of 3-acetoacetyl benzopyranopyridones with different hydrazines. All compounds were characterised on the basis of spectral data and their antibacterial activity evaluated.     

Enzyme catalysis: tool to make and break amygdalin hydrogelators from renewable resources: a delivery model for hydrophobic drugs

We report a novel approach for the controlled delivery of an antiinflammatory, chemopreventive drug by an enzyme-triggered drug release mechanism via the degradation of encapsulated hydrogels. The hydro- and organogelators are synthesized in high yields from renewable resources by using regioselective enzyme catalysis, and a known chemopreventive and antiinflammatory drug, i.e., curcumin, is used for the model study. The release of the drug occurred at physiological temperature, and control of the drug release rate is achieved by manipulating the enzyme concentration and/or temperature. The byproducts formed after the gel degradation were characterized and clearly demonstrated the site specificity of degradation of the gelator by enzyme catalysis. The present approach could have applications in developing cost-effective controlled drug delivery vehicles from renewable resources, with a potential impact on pharmaceutical research and molecular design and delivery strategies.     

Rapid method for accurate analysis of melatonin, serotonin and auxin in plant samples using liquid chromatography-tandem mass spectrometry

Currently, the information available on the physiological functions of melatonin in higher plants is rather limited and the role of plant melatonin in human health remains undetermined. Research in this area has been slow due to lack of efficient analytical methods for rapid identification and quantification of the melatonin and related compounds in complex plant matrices. In this communication, we report the development of a rapid, accurate method for extraction, detection and quantification of plant melatonin, serotonin and indole-3-acetic acid (IAA) by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI), respectively. The limit of detection (LOD) of melatonin in the plant extraction was 5 pg/ml and the limit of quantification (LOQ) was 0.02 ng/ml, as well as LOD for serotonin was 100 pg/ml and the LOQ was 5 ng/ml, LOD for IAA was 50 pg/ml and the LOQ was 0.7 ng/ml. There was a linear relationship between melatonin, serotonin, and IAA concentration and peak area over a quantifiable range of 0.02 ng/ml to 0.1 mg/ml, 5 ng/ml to 0.1 mg/ml, and 0.7 ng/ml to 0.1 mg/ml, respectively, in the plant extract.     

Synthesis and Mechanistic Study of Triheterocyclic 4H‐Pyrimido[2,1‐b]benzothiazole derivatives,One‐Pot Three‐component Reaction under Solvent‐Free Conditions

An efficient method has been developed for the preparation of 4H‐pyrimido[2,1‐b]benzothiazole derivatives by the condensation of aldehydes, β‐ketoester, and 2‐amino benzothiazole under solvent and solvent‐free conditions using various catalysts. The reaction uses benzothiazole as a new component, and good yield is obtained at 60–65°C under solvent‐free conditions. Atom economies, good yield, environmentally benign, and easy to work‐up are some of the important features of this protocol. The present study suggests that acetic acid and metal catalysts follow different mechanism. In acetic acid, 2‐amino benzothiazole reacts with benzaldehyde, and resultant intermediate reacts with ethyl acetoacetate to give final product, whereas in the presence of metal catalysts, 2‐amino benzothiazole first reacts with ethyl acetoacetate, and resultant intermediate reacts with benzaldehyde to give pyrimido[2,1‐b]benzothiazole.     

Noncovalent Macromolecular Architectures of Oligo(p-phenylenevinylene)s (OPVs): Role of End Functional Groups on the Gelation of Organic Solvents

Summary: Self-assembly of a few OPV derivatives having different end functional groups to aggregates, fibrous networks and organogels are discussed. OPV1 and OPV2 functionalized with ester moieties form gels in nonpolar hydrocarbon solvents whereas OPV3 with carboxylic acid groups form gel from THF and dichloromethane. OPV4 with dicyano moieties form aggregates but could not gelate solvents. AFM and TEM studies revealed considerable difference in the morphology of the self-assembled structures of OPV1-4 . From the optical, morphological and gelation data it is concluded that the nature of the end functional groups strongly influences upon the self-assembly and gelation properties of OPVs.