A comparative study of the IR spectra of alkaloids containing piperidine and quinolizidine rings in the 2500–2830 cm−1 region
Summary1. A comparative method of studying the conformational states of alkaloids of the piperidine and quinolizidine series by comparing the intensities of the IR bands in the 2500–2830 cm−1 region in the solid and liquid states has been proposed.2. It has been shown that the process of inversion and other labile conformational transformations affect the number, frequency, and intensity of the vibrational transitions in the “Bohlmann region.”
Conformation of the C15 lupine alkaloids
Methods have been developed for preparing 17α-deuterio-, 17β-deuterio-, and l7-dideuteriolupanines. The nuclear magnetic resonance and infrared spectra of these provided strong evidence that ring C in the alkaloid is in a boat conformation in solution. Reduction of these compounds to the deuterated sparteines confirmed the same geometry for sparteine. In contrast, moilodeuteration of aphylline at C-17 showed that i t had an all-chair conformation in solution. 13β-Hydroxylupanine was shown to have the same conformation as lupanine in solution, but to adopt an all-chair conformation in the solid state. Interpretation of the nuclear magnetic resonance spectra enabled the conformation of ring C of 15-oxosparteine to be assigned. The oxidation and reductions involving C-17 of lupanine have been shown to be highly stereospecific, and an interpretation is given of the difference betmeen the dehydrogenation of lupanine by mercuric acetate and those by Nbromosuccinimide or by the mercuric acetate - ethylenediatnin...
Pharmacokinetics of amikacin and chloramphenicol in the aqueous humor of rabbits
Composite data describing ocular pharmacokinetics are unreliable because of intersubject variation. To address this problem, an animal model was developed in which multiple aqueous samples from single subjects were obtained. Following direct anterior chamber or intravenous administration of amikacin or chloramphenicol, pharmacokinetic analysis of drug concentrations in the serum and anterior chamber was performed by using a nonlinear least-squares regression program. The number of anterior chamber paracenteses performed did not alter the beta elimination rates or percent penetration into the anterior chamber. The aqueous humor and peripheral-compartment terminal slopes were identical. These data indicate that complete ocular concentration-time curves can be obtained without altering antibiotic pharmacokinetics. Following direct injection into the anterior chamber, the elimination rates for both antibiotics followed a one-compartment model, whereas those following intravenous administration best fit an open, first-order, two-compartment model. Following intravenous administration, the anterior chamber elimination rate constants for both drugs were equal to that of the serum and significantly longer than that following direct injection. The elimination rates of both drugs following direct injection were similar. Systemic administration resulted in drug levels in aqueous humor that persisted longer than those following direct injection. Chloramphenicol, a lipophilic compound, gave higher mean concentrations in aqueous humor than did amikacin. Our model provides a new approach which rigorously examines ocular pharmacokinetics and provides data which suggest that for selected compounds the parenteral route of administration is preferable.