Cytotoxic activity and DNA binding of naphthalimide derivatives with amino acid and dichloroacetamide functionalizations

A series of novel naphthalimide derivatives modified by amino acids and their dichloroacetamide derivatives at the 3-position have been synthesized. Their cytotoxic activities were preliminarily evaluated against Hela, A549 and K562 cells, which showed that the length of the side chains of the amino acids influenced the cytotoxic activities. Moreover, compound 7d showed a very good cytotoxic activity against A549 cells with an IC50 value of 4.78 mmol Là1. Furthermore, the UV–vis, fluorescence,and circular dichroism(CD) spectroscopies and thermal denaturation experiment indicated that compounds 6a, 6d and 7a, 7d, as DNA intercalators, exhibited binding affinities with calf-thymus DNA(Ct-DNA).     

Pyrimidine derivatives. VI. Synthesis of mono-, di-, tri-, and tetrabromo-substituted pyrimidine derivatives

The following bromo-2,4(1H,3H)-pyrimidinediones possessing a bromo substituent at the 5-position and side chains at the 1- and 6-positions were prepared. The three types of mono-bromo derivatives are: 1-(bromoalkyl)-3,6-dimethyl- 3a-d , 5-bromo-3,6-dimethyl-1-(hydroxyalkyl)- 4a-d , and 1-(acetoxyalkyl)-5-bromo-3,6-dimethyl-2,4(1H,3H)-pyrimidinediones 11a-d . The three types of dibromo derivatives are: 5-bromo-1-(bromoalkyl)-3,6-dimethyl- Sa-d , 1-(acetoxyalkyl)-5-bromo-6-bromomethyl- 8a, 8c , and 8d , and 5-bromo-6-bromomethyl 1-(hydroxyalkyl)-2,4(1H,3H)-pyrimidinediones 9a, 9c , and 9d . Likewise one group of tribromo and one group of tetrabromo derivatives are: 5-bromo-1-(bromoalkyl)-6-bromomethyl -7a-d and 5-bromo-1-(bromoalkyl)-6-dibromomethyl-2,4(1H,3H)-pyrimidinediones 6a-d .     

Synthesis and antidiabetic activity of novel triazole derivatives containing amino acids

New series of triazole derivatives coupled with amino acids 1a-h were obtained via multicomponent reaction of 2-hydroxy benzaldehyde or 2-hydroxy acetophenone with thiosemicarbazide and different amino acids. The obtained compounds were reacted with p-toluinesulfonyl chloride 2 to give the corresponding sulfonamides 3a-h . Compound 1b was allowed to react with different aromatic aldehydes or cyclic ketone under alkaline conditions to afford the expected imino compounds 4a-d and 6a-c , respectively. These compounds were allowed to react with ethyl glycolate to yield the expected thiazolidinone derivatives 5a-d or 7a-c , respectively. Structures of the newly synthesized compounds were found to be in accordance with their elemental analyses and spectral data. The obtained compounds exhibited very prominent in vitro and in vivo antihyperglycemic effect at a dose of 40 mg/kg body weight compared to the standard drug gliclazide and control. The antidiabetic effect was investigated using oral glucose tolerance test in normal and non-insulin-dependent diabetes mellitus (NIDDM) in STZ-rat model. Compounds 3a - h , 5b , 5c , 5d , 7a , 7b , and 7c showed significant activity in lowering blood glucose (more than 80%) compared to the NIDDM control.     

Efficient peptide coupling involving sterically hindered amino acids

Hindered amino acids have been introduced into peptide chains by coupling N-(Cbz- and Fmoc-alpha-aminoacyl)benzotriazoles with amino acids, wherein at least one of the components was sterically hindered, to provide compounds 3a-e, (3c +3 c'), 5a-d, (5a + 5a'), 6a-c, (6b + 6b'), 8a-c, 9a-e, 10a-d, and (10a + 10a') in isolated yields of 41-95% with complete retention of chirality as evidenced by NMR and HPLC analysis. The benzotriazole activation methodology is a new route for the synthesis of sterically hindered peptides. (Note: compound numbers written within brackets represent diastereomeric mixtures or racemates; compound numbers without brackets represent enantiomers.).     

Contributions of hydroxyethyl groups to the DNA binding affinities of anthracene probes

Contributions of hydroxyethyl functions to the DNA binding affinities of substituted anthracenes are evaluated by calorimetry and spectroscopy. Isothermal titration calorimetry indicated that binding of the ligands to calf thymus DNA (5 mM Tris buffer, 50 mM NaCl, pH 7.2, 25 degrees C) is exothermic. The binding constants increased from 1.5 x 10(4) to 1.7 x 10(6) M(-1) as a function of increase in the number of hydroxyethyl functions (0-4). DNA binding was accompanied by red-shifted absorption (approximately 630 cm(-1)), strong hypochromism (>65%), positive induced-circular dichroism bands, and negative linear dichroism signals. DNA binding, in general, increased the helix stabilities to a significant extent (DeltaT(m) approximately 7 degrees C, DeltaDeltaH approximately 3 kcal/mol, DeltaDeltaS approximately 6-20 cal/K.mol). The binding constants showed a strong correlation with the number of hydroxyethyl groups present on the anthracene ring system. Analysis of the binding data using the hydrophobicity parameter (Log P) showed a poor correlation between the binding affinity and hydrophobicity. This observation was also supported by a comparison of the affinities of probes carrying N-ethyl (Kb = 0.8 x 10(5) M(-1)) versus N-hydroxyethyl side chains (Kb = 5.5 x 10(5) M(-1)). These are the very first examples of a strong quantitative correlation between the DNA binding affinity of a probe and the number of hydroxyethyl groups present on the probe. These quantitative findings are useful in the rational design of new ligands for high-affinity binding to DNA.     

Improving Gene Delivery Efficiency of Bioreducible Poly(amidoamine)s via Grafting with Dendritic Poly(amidoamine)s

Dendritic poly(amidoamine)s (PAMAM)s were introduced into the side chains of disulfide‐containing poly(amidoamine)s via repetitive Michael addition and amidation. The bioreducible poly(amidoamine)s grafted with dendritic polyamidoamines showed high buffer capacity, low cytotoxicity and strong DNA binding ability at low N/P ratio. They were able to condense DNA into small sized polycation/DNA complexes, which degraded and released the incorporated DNA under reductive conditions. In comparison to the original disulfide‐containing poly(amidoamine) with aminoethyl side chain, the grafting of the bioreducible poly(amidoamine) with dendrimer greatly improved the transfection efficiencies of 293T and HeLa cells with foreign DNA at various N/P ratios. The structure–gene delivery property relations of dendrimer‐grafted polycations will provide valuable insight into the design of highly efficient and less toxic polycationic gene carriers.

     

Quantifying the role of water in protein-carbohydrate interactions

Water-mediated interactions play a key role in carbohydrate-lectin binding, where the interactions involve a conserved water that is separated from the bulk solvent and present a bridge between the side chains of the protein and the carbohydrate ligand. To apply quantum mechanical methods to examine the role of conserved waters, we present an analysis in which the relevant carbohydrate atoms are modeled by methanol, and in which the protein is replaced by a limited number of amino acid side chains. Clusters containing a conserved water and a representative amino acid fragment were also examined to determine the influence of amino acid side chains on interaction energies. To quantify the differential binding energies of methanol versus water, quantum mechanical calculations were performed at the B3LYP/6-311++G(3df,3pd)//B3LYP/6-31+G(d) level in which either a methanol molecule was bound to the conserved water (liganded state) or in which a water molecule replaces the methanol (unliganded state). Not surprisingly, the binding of a water to clusters containing charged amino acid side chains was more favorable by 1.55 to 7.23 kcal/mol than that for the binding of a water to the corresponding pure water clusters. In contrast, the binding energy of water to clusters containing polar-uncharged amino acid side chains ranged from 4.35 kcal/mol less favorable to 4.72 kcal/mol more favorable than for binding to the analogous pure water clusters. The overall trend for the binding of methanol versus water, in any of the clusters, favored methanol by an average value of 1.05 kcal/mol. To extend these studies to a complex between a protein (Concanavalin A) and its carbohydrate ligand, a cluster was examined that contained the side chains of three key amino acids, namely asparagine, aspartate, and arginine, as well as a key water molecule, arranged as in the X-ray diffraction structure of Con A. Again, using methanol as a model for the endogenous carbohydrate ligand, energies of -5.94 kcal/mol and -5.70 kcal/mol were obtained for the binding of methanol and water, respectively, to the Con A-water cluster. The extent to which cooperativity enhanced the binding energies has been quantified in terms of nonadditive three-body contributions. In general, the binding of water or methanol to neutral dimers formed cooperative clusters; in contrast, the cooperativity in charged clusters depended on the overall geometry as well as the charge.     

Synthesis of anticancer compounds, III (Bioorg Med Chem Lett 17, 6091, 2007), carbinol derivatives of azanaphthoquinone annelated pyrroles

Abstract  

A series of carbinols has been synthesized by attachment of different piperidinyl side chains to the quinone structure of azanaphthoquinone annelated pyrroles. The synthesized compounds were screened for their cytotoxic activities. Compared to previously published results, they exhibited only moderate activities, thus showing that the existence of the quinone moiety seems to be essential for anticancer activities of this group.     

Synthesis of thiazo- or thiadiazo- naphthalene carboxamides via mercuric intermediates and their antitumor and DNA photocleavage activities

Two kinds of thiazo- or thiadiazo- naphthalene carboxamides with aminoalkyl side chains at 5- or 6-position modified from naphthalimides were designed, synthesized and quantitatively evaluated as antitumor and DNA photocleaving agents. The compound with aminoalkyl side chain at 6-position showed stronger antitumor (A549, P388) and DNA photocleaving abilities than its isomer with that at 5-position. B₂, the most efficient DNA photocleaver, also exhibited the highest cytotoxicity with the IC₅₀ of 2.53 and 0.11 μM against cell lines of A549 and P388, respectively. These compounds also photocleaved DNA more efficiently than their corresponding naphthalimides.     

Evaluation of metal-mediated DNA binding of benzoxazole ligands by electrospray ionization mass spectrometry

The binding of a series of benzoxazole analogs with different amide- and ester-linked side chains to duplex DNA in the absence and presence of divalent metal cations is examined. All ligands were found to form complexes with Ni2+, Cu2+, and Zn2+, with 2:1 ligand/metal cation binding stoichiometries dominating for ligands containing shorter side chains (2, 6, 7, and 8), while 1:1 complexes were the most abundant for ligands with long side chains (9, 10, and 11). Ligand binding with duplex DNA in the absence of metal cations was assessed, and the long side-chain ligands were found to form low abundance complexes with 1:1 ligand/DNA binding stoichiometries. The ligands with the shorter side chains only formed DNA complexes in the presence of metal cations, most notably for 7 and 8 binding to DNA in the presence of Cu2+. The binding of long side-chain ligands was enhanced by Cu2+ and to a lesser degree by Ni2+ and Zn2+. The cytotoxicities of all of the ligands against the A549 lung cancer and MCF7 breast cancer cell lines were also examined. The ligands exhibiting the most dramatic metal-enhanced DNA binding also demonstrated the greatest cytotoxic activity. Both 7 and 8 were found to be the most cytotoxic against the A549 lung cancer cell line and 8 demonstrated moderate cytotoxicity against MCF7 breast cancer cells. Metal ions also enhanced the DNA binding of the ligands with the long side chains, especially for 9, which also exhibited the highest level of cytotoxicity of the long side-chain compounds.     

Synthesis of diverse (E)-2-((1H-imidazol-1-yl)methyl)-2-((benzyloxy)methyl)-2,3-dihydro-1H-inden-1-one O-benzyl oxime derivatives as potent antileishmanial agents

A series of (E)-2-((1H-imidazol-1-yl)methyl)-2-((benzyloxy)methyl)-2,3-dihydro-1H-inden-1-one O-benzyl oximes ( 6a-j ) were prepared and evaluated for their in vitro antileishmanial potency against Leishmania donovani (in promastigote and amastigote models). At a concentration of 05-μg/mL, compounds 3a-d , 4a-d , 5a , 5b , 6a-d, and 7a-d exhibited 97% to 100% and 87% to 100% inhibition against promastigotes and amastigotes, respectively. Compounds 6a , 6d-6j and 6a , 6i , 6j exhibited equal antileishmanial potency to that of SSG and Pentamidin at lower values of IC₅₀.     

Synthesis and preliminary antimicrobial activities of new arylideneamino-1,3,4-thiadiazole-(thio/dithio)-acetamido cephalosporanic acids

New derivatives of 7-aminocephalosporanic acid 1-8 were synthesized by acylation of the 7-amino group of the cephem nucleus with various arylidinimino-1,3,4-thiadiazole-thio(or dithio)-acetic acid intermediates 3a-d and 5a-d, respectively, so the acyl side chains of these new cephalosporins contained a sulfide or disulfide bond. This unique combination of a Schiff base with the sulfide or disulfide bonds in the acyl side chain afforded new cephalosporins of reasonable potencies, some of which were found to possess moderate activities against the tested microorganisms. Their chemical structures were characterized by 1H-NMR, IR spectroscopy and elemental microanalysis. Preliminary in vitro antimicrobial activities of the prepared cephalosporins were investigated using a panel of selected microorganisms. Results indicated that the newly synthesized cephalosporins containing disulfide bonds (compounds 5-8) exhibited better activities against Staphylococcus aureus and Escherichia coli. The cephalosporins cross-linked by a sulfide bond (compounds 1-4) showed a slight change in antimicrobial activities when compared with that of the reference cephalosporin (cephalexin).     

Tunable inhibition and denaturation of alpha-chymotrypsin with amino acid-functionalized gold nanoparticles

Water-soluble gold nanoparticles bearing diverse l-amino acid terminals have been fabricated to probe the effect of receptor surface on protein surface binding. The interaction of these nanoparticles with alpha-chymotrypsin (ChT) was investigated by activity assay, gel electrophoresis, zeta-potential, circular dichroism, and fluorescence spectroscopy. The results show that both electrostatic and hydrophobic interactions between the hydrophobic patches of receptors and the protein contribute to the stability of the complex. The microscopic binding constants for these receptor-protein systems are 10(6)-10(7) M(-1), with the capacity of the nanoparticle receptors to bind proteins determined by both their surface area and their surface charge density. Furthermore, it is found that the hydrophilic side chains destabilize the ChT structure through either competitive hydrogen bonding or breakage of salt bridges, whereas denaturation was much slower with hydrophobic amino acid side chains. Significantly, correlation between the hydrophobicity index of amino acid side chains and the binding affinity and denaturation rates was observed.     

Synthesis of novel apio carbocyclic nucleoside analogues as selective a(3) adenosine receptor agonists

On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine (apio-ddA), novel apio-neplanocin A analogues 5a-d, combining the properties of two nucleosides, were stereoselectively synthesized. The apio moiety of the target nucleosides 5a-d was stereoselectively introduced by treating lactol 10 with 37% formaldehyde in the presence of potassium carbonate. The carbasugar moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs catalyst in methylene chloride. The final nucleosides 5a-d were synthesized from the condensation of the glycosyl donor 14 with nucleic bases under the standard Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio-methanocarbaadenosine 7 were derived from the common intermediate 13 using catalytic hydrogenation and Simmons-Smith cyclopropanation as key steps. All of the final nucleosides 5a-d, 6, and 7 did not show significant inhibitory activity against S-adenosylhomocysteine hydrolase (SAH) up to 100 muM, maybe due to the absence of the secondary hydroxyl group at the C3'-position, which should be oxidized by cofactor-bound NAD(+). However, apio-neplanocin A (5a) showed potent and highly selective binding affinity (K(i) = 628 +/- 69 nM) at the A(3) adenosine receptor without any binding affinity at the A(1) and A(2A) adenosine receptors. In conclusion, we have first developed novel carbocyclic nucleosides with unnatural apio-carbasugars using stereoselective hydroxymethylation and RCM reaction and also discovered a new template of human A(3) adenosine receptor agonist, which play a great role in developing new A(3) adenosine receptor agonist as well as in identifying the binding site of the receptor.     

sp carbon chains surrounded by sp(3) carbon double helices: directed syntheses of wirelike Pt(CC)(n)Pt moieties that are spanned by two P(CH(2))(m)P linkages via alkene metathesis

Reactions of trans-(C6F5)(Ph2P(CH2)m'CH=CH2)2PtCl (1; m' = a, 6; b, 7; c, 8; d, 9; e, 10) and H(CC)2H (HNEt2, cat. CuI) give trans-(C6F5)(Ph2P(CH2)m'CH=CH2)2Pt(CC)2H (3a-e, 80-95%). Oxidative homocouplings of 3a-d under Hay conditions (O2, cat. CuCl/TMEDA, acetone) yield trans,trans-(C6F5)(Ph2P(CH2)m'CH=CH2)2Pt(CC)4Pt(Ph2P(CH2)m'CH=CH2)2(C6F5) (4a-d, 64-84%). Treatment of 3c-e with excess HCCSiEt3 under Hay conditions gives trans-(C6F5)(Ph2P(CH2)m'CH=CH2)2Pt(CC)3SiEt3 (56-73%). Homocouplings (n-Bu4N+ F-, Me3SiCl, Hay conditions) afford trans,trans-(C6F5)(Ph2P(CH2)m'CH=CH2)2Pt(CC)6Pt(Ph2P(CH2)m'CH=CH2)2(C6F5) (13c-e, 59-64%). Reactions of 4a-d and 13c-e with Grubbs' catalyst, followed by hydrogenation, give mixtures of trans,trans-(C6F5)(Ph2P(CH2)mPPh2)Pt(CC)nPt(Ph2P(CH2)mPPh2)(C6F5) with termini-spanning diphosphines and trans,trans-(C6F5)(Ph2P(CH2)mPPh2)Pt(CC)nPt(Ph2P(CH2)mPPh2)(C6F5) with trans-spanning diphosphines (m = 2m' + 2; n = 4, 6). The latter (n = 4) are independently synthesized by similar metatheses/hydrogenations of 1a-d to give trans-(C6F5)(Ph2P(CH2)mPPh2)PtCl (49-59%), followed by analogous introductions of (CC)4 chains (66-77%). Crystal structures of complexes with termini-spanning diphosphines show sp3 chains with both double-helical (m/n = 20/4) and nonhelical (m/n = 20/6) conformations, and highly shielded sp chains. The sp3 chains of complexes with trans-spanning diphosphines exhibit double half-clamshell conformations. The dynamic properties of both classes of molecules are analyzed in detail.     

Structural and energetic effects in the molecular recognition of protonated peptidomimetic bases by 18-crown-6

Absolute 18-crown-6 (18C6) affinities of nine protonated peptidomimetic bases are determined using guided ion beam tandem mass spectrometry techniques. The bases (B) included in this work are mimics for the n-terminal amino group and the side chains of the basic amino acids, i.e., the favorable sites for binding of 18C6 to peptides and proteins. Isopropylamine is chosen as a mimic for the n-terminal amino group, imidazole and 4-methylimidazole are chosen as mimics for the side chain of histidine (His), 1-methylguanidine is chosen as a mimic for the side chain of arginine (Arg), and several primary amines including methylamine, ethylamine, n-propylamine, n-butylamine, and 1,5-diamino pentane as mimics for the side chain of lysine (Lys). Theoretical electronic structure calculations are performed to determine stable geometries and energetics for neutral and protonated 18C6 and the peptidomimetic bases, as well as the proton bound complexes comprised of these species, (B)H(+)(18C6). The measured 18C6 binding affinities of the Lys side chain mimics are larger than the measured binding affinities of the mimics for Arg and His. These results suggest that the Lys side chains should be the preferred binding sites for 18C6 complexation to peptides and proteins. Present results also suggest that competition between Arg or His and Lys for 18C6 is not significant. The mimic for the n-terminal amino group exhibits a measured binding affinity for 18C6 that is similar to or greater than that of the Lys side chain mimics. However, theory suggests that binding to n-terminal amino group mimic is weaker than that to all of the Lys mimics. These results suggest that the n-terminal amino group may compete with the Lys side chains for 18C6 complexation.     

Structures, photoluminescence, and reversible vapoluminescence properties of neutral platinum(II) complexes containing extended pi-conjugated cyclometalated ligands

Reacting K2PtCl4 with the tridentate R-C(wedge)N(wedge)C-H2 ligands 2,6-di-(2'-naphthyl)-4-R-pyridine (R = H, 1a; Ph, 1b; 4-BrC6H4, 1c; 3,5-F2C6H3, 1d) in glacial acetic acid, followed by heating in dimethyl sulfoxide (DMSO), gave complexes [(R-C(wedge)N(wedge)C)Pt(DMSO)] (2a-d). In the crystal structures of 2a-c, the molecules are paired in a head-to-tail orientation with Pt...Pt separations >6.3 A, and there are extensive close C-H...pi (d = 2.656-2.891 A), pi...pi (d = 3.322-3.399 A), and C-H...O=S (d = 2.265-2.643 A) contacts. [(Ph-C(wedge)N(wedge)C)Pt(PPh3)] (3) was prepared by reacting 2b with PPh3. Reactions of 2a-d with bis(diphenylphosphino)methane (dppm) gave [(R-C(wedge)N(wedge)C)2Pt2(mu-dppm)] (4a-d). Both head-to-head (syn) and head-to-tail (anti) conformations were found for 4a.6CHCl3.C5H12, whereas only one conformation was observed for 4b.2CHCl3 (syn), 4c.3CH2Cl2 (syn), and 4d.2CHCl3 (anti). In the crystal structures of 4a-d, there are close intramolecular Pt...Pt contacts of 3.272-3.441 A in the syn conformers, and long intramolecular Pt...Pt separations of 5.681-5.714 A in the anti conformers. There are weak C-H...X (d = 2.497-3.134 A) and X...X (X = Cl or Br; d = 2.973-3.655 A) interactions between molecules 4a-d and occluded CHCl3/CH2Cl2 molecules, and their solvent channels are of varying diameters (approximately 9-28 A). Complexes 2a-d, 3, and 4a-d are photoluminescent in the solid state, with emission maxima at 602-643 nm. Upon exposure to volatile organic compounds, 4a shows a fast and reversible vapoluminescent response, which is most intense with volatile halogenated solvents (except CCl4). Powder X-ray diffraction analysis of desolvated 4a revealed a more condensed molecular packing of syn and anti complexes than crystal 4a.6CHCl3.C5H12.     

Thermally Stabilized Blue Luminescent Poly(p‐phenylene)s Covered with Polyhedral Oligomeric Silsesquioxanes

A novel series of poly(p‐phenylene)s (PPPs) with polyhedral oligomeric silsesquioxanes (POSSs) on their side chains was prepared. The obtained POSS‐modified PPPs are as follows: 25POSS‐PPP ( 2b , containing 25 mol‐% of POSS units in all side chains), 50POSS‐PPP ( 2c , containing 50 mol‐% of POSS units in all side chains), 100POSS‐PPP ( 2d , containing 100 mol‐% of POSS units in all side chains), and 0POSS‐PPP ( 2a , as a blank polymer). Films polymer 2d showed the same absorption and photoluminescence (PL) spectra as those in CHCl₃ solution, indicating that bulky POSS units strongly suppressed intermolecular aggregation of the PPP backbone. Polymer 2d showed the same PL spectra even after thermal annealing at 150 °C for 6 h. This enhancement of PL stability is due to the significant effect of the bulky POSS units.

     

Deoxysugars via microbial reduction of 5-acyl-isoxazolines: application to the synthesis of 3-deoxy-D-fructose and derivatives

5-Acylisoxazolines 3a-d were obtained by 1,3-dipolar cycloaddition from acetoxymethyl vinyl ketone and nitro precursors. Compounds 3a-d were biotransformed by Aspergillus niger into a 1:1 mixture of stereomers of 5-dihydroxyethyl isoxazolines (+)-4a-d (anti) and (-)-5a-d (syn). Both stereomers were obtained in good yields and with high optical purities. Carbonyl reduction by Aspergillus niger produces alcohols of R-configuration thus giving an access to D-sugar analogues: Compound (+)-4d was converted to 3-deoxy-D-erythro-hexulose and several protected derivatives. Total synthesis of 3-deoxy-D-fructose-6-phosphate was also achieved in two steps and 64% overall yield from (+)-4d.     

Preparation and antimicrobial studies of acyclic sulfamates.

A series of acyclic sulfamates have been prepared and tested for antimicrobial activity. Thus, the oxysulfonyl isocyanates, ROSO2NCO (1a, R = 4-methoxyphenyl; 1b, R = phenyl; 1c, R = 4-chlorophenyl and 1d, R = 2,2,2-trifluoroethyl) have been prepared in 76-91% yield from chlorosulfonyl isocyanate. Treatment of 1a-d with glycidol gave the glycidyl carbamates 2a d. Internal cyclisation afforded the corresponding 4-hydroxymethyl-2-oxazolidinones 3a-d, which in turn were hydrolysed to give the free amino alcohols 4a-d. The yields were in the range 39-85%. A preliminary agar diffusion test of 2a-d, 3a-d, 4a-d indicated 2a-d and 3c to be possible antimicrobial agents. A more thorough analysis of these compounds revealed a minimum inhibition concentration (MIC) of 128 and 64 mg l-1 for glycidyl p-methoxyphenoxysulfonylcarbamate (2a) and glycidyl phenoxysulfonylcarbamate (2b) respectively, against Branhamella catarrhalis.