Charles F. Hammer

Reactions of β-substituted amines—II: Nucleophilic displacement reactions on 3-chloro-1-ethylpiperidine

Abstract Synthetic, kinetic and optical activity studies have established that 3-chloro-1-ethylpiperidine undergoes nucleophilic displacement reactions in solution by a two-step, neighboring group participation mechanism. Nitrogen displaces chloride internally, to give an ambident bicyclic aziridinium ion which then reacts with nucleophiles to give pyrrolidine and piperidine isomers. The aziridinium ion. 1-ethyl-1-azoniabicyclo[3.1.0]hexane perchlorate, has been synthesized separately.

A homogeneous immunoassay for the mycotoxin T-2 utilizing liposomes, monoclonal antibodies, and complement

The trichothecene mycotoxin T-2 is a fungal metabolite known to contaminate agricultural products and cause intoxication of humans and animals. We have developed a homogeneous competition inhibition assay for T-2 mycotoxin based on complement-mediated lysis of liposomes. The T-2 mycotoxin was converted to an acid chloride derivative, subsequently coupled to the amino group of phosphatidylethanolamine, and incorporated with the phospholipid into unilamellar liposomes. Carboxyfluorescein, which is self-quenched at high concentrations, was entrapped in the liposomes as a release marker. We used a monoclonal IgG1 antibody specific for T-2 mycotoxin and a polyclonal anti-mouse Ig as a secondary antibody since the anti-T-2 IgG1 does not activate complement. In the absence of free T-2, the liposomes were lysed within 30 min after the addition of complement, releasing carboxyfluorescein into the surrounding buffer. In the presence of free T-2 toxin, the binding of antibodies to the liposomes was reduced, causing a corresponding decrease in lysis. This assay proved to be sensitive to T-2 toxin levels as low as 2 ng, which is 10-fold more sensitive than the present enzyme immunoassay using the same antibodies.

Aspartato(1,2-cyclohexanediamine)platinum(II) complexes: synthesis and characterization; effects of minor impurities on antitumor activity

Abstract Aspartato(1,2-cyclohexanediamine)platinum(II) (ADP), where 1,2-cyclohexanediamine (DAC) is either trans-RR-, trans-SS-, meso-RS-, or a mixture of the three isomers (ADP mixture), has been synthesized and evaluated for antitumor activity. The structures of the complexes have been characterized by various spectroscopic techniques (IR, 1H, 13C, 195Pt and 2D-COSY (1H{1H}) and 2D-HETCOSY (1H{13C}) NMR). Purification and murine antitumor activity of the individual ADP isomers indicate that minor impurities in the ADP mixture have a significant effect on the potency of the platinum complexes.

The action of bromine on Δ7-ergostene and choletene derivatives

Abstract The major product, obtained in yields up to 50% from the action of bromine on 5-dihydroergosteryl acetate (ergosta-7,22-dien-38-yl acetate) is 7,11,22a,23a-tetrabromoergost-8-en-38-yl acetate. It is accompanied by an isomer, 7,8,22a,23a-tetrabromoergost-14-enyl and other Δ 7,22 -ergostadienyl esters in described. Nuclear magnetic resonance chemical shifts of the angular methyl group protons are reported for represented classes and compared with calculated values.

NMR studies of the stereospecificity of 20β-hydroxysteroid dehydrogenase

Abstract We (3,4) previously observed the reduction of 21-dehydrocorticosteroids in the presence of 20β-hydroxysteroid dehydrogenase proceeded at a faster rate than the reduction of the corresponding corticosteroids. The presence of adjacent carbonyl groups suggested the possibility that the increased rate of reduction of the 20-one,21-a1 steroid analogs resulted from a lack of specificity of the enzyme 20β-hydroxysteroid dehydrogenase for either the aldehyde or ketone group. Nuclear magnetic resonance spectroscopy indicated that the angular methyl groups of the steroid were sensitive probes for the constituents on the basic steroid skeleton. The C 18 methyl resonance of 17,21-dihydroxy-4-pregnene-3,20-dione and 17-hydroxy-3,20-dioxo-4-pregnene-21-a1 were 0.722 ppm and 0.728 ppm respectively. The magnitude and sign of the change in chemical shift of the C 18 methyl resonance for the enzymatic products of 17,21-dihydroxy-4-pregnene-3,20-dione and 17-hydroxy-3,20-dioxo-4-pregnene-21-a1 (+0.135 ppm and +0.144 ppm respectively) were consistent with a stereochemical assignment of 20β-hydroxyl.

REACTIONS OF THE FLUORINATING AGENT CF3OF WITH AMINO ACID DERIVATIVES AND PEPTIDES

Abstract A number of Hydrophobic acyl amino acid esters were fluorinated using CF 3 OF, yielding N -fluoroamides. The 1 H, 13 C and 19 F nuclear magnetic resonance (NMR) data for these compounds are reported. The first 14 N NMR spectrum of an N -fluoroamide is also reported, namely that of N -acetyl- N -fluoroglycine ethyl ester. The 14 N resonance of the fluorinated compound was shifted downfield by over 100 ppm from that of the starting material. Reaction of CF 3 OF with N -acetylleucine ethyl ester yielded the N -fluoroamide, as well as the compound in which the γ-hydrogen of leucine is replaced by fluorine. Treatment of the cyclopentapeptide c-(gly-pro-gly- d -ala-pro) with CF 3 OF yielded an intractable mixture of fluorinated hydrocarbons, N -fluoroamides and difluoroamides. Separation of the mixture resulting from treatment of N -acetylproline with CF 3 OF led to recovery of a fraction whose 19 F NMR spectrum indicated fluorination at the proline nitrogen and subsequent opening of the proline ring. Treatment of the cyclopentapeptide c- (gly-leu-gly-gly-gly) with CF 3 OF proceeded to a very limited extent, with the resulting mixture of N -fluoroamides showing no preference for fluorination at a specific site.