Tetracyclic diterpenoids with a new carbon skeleton forming products of the cyclization of labdane diterpenoids
From the product of the cyclization of a mixture of isomeric ent-copalols (i) [i] with a mixture of formic and concentrated acids, we have isolated an oxygen-containing fraction (yield 47%) consisting of a mixture of five alcohols and their formates. Three of the alcohols proved to be known: isoagath-12-en-15-ols epimeric at Cz4 [2] and 14~-hibanol [3]. For the other two alcohols, with the composition C2oH3~O, structures (2) and (3) were shown, these being based on a new carbon skeleton [4].
Cationic cyclization of bicyclic diterpenes
Manool and agathadiol cyclize in formic acid to the 13-epimeric pimara-8,15-dienes and 14α-hydroxyhibane derivatives. The mechanistic and biosynthetic implications of these results are discussed in relation to other work involving cations in tetracyclic diterpenes. The nuclear magnetic resonance spectra of relevant tricyclic and tetracyclic diterpenes are documented.
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.