Addition of pyridine-N-imine to a variety of acetylenic mono-(Scheme I) and di-(Scheme 11) carboxylic ester dipolarophiles was carried out. Several of the 3-azapyrrocoline esters obtained were further converted into acids, amides and hydrazides as shown in Schemes I and 11.
Twonovel antifungal agents, lanomycin and glucolanomycin, as well as a biologically inactive degradation product, lanomycinol, were isolated from liquid fermentations of Pycnidiophora dispersa.All three compoundsshare an £,£,£-triene appendedto a pyran ring. Lanomycincontains a glycine ester and glucolanomycin possesses a glucose unit attached to the glycine nitrogen. The structures, including absolute stereochemistry, were determined by spectroscopic analysis and partial chemical degradation. Both of the glycine containing compounds show activity against several pathogenic fungi in vitro.In the course of our antifungal screening program, two compounds, lanomycin and glucolanomycin, were identified with activity against Candida species and dermatophytes. These compoundswere found to be inhibitors of the cytochrome P-450 enzyme, lanosterol demethylase. The compounds were isolated from fermentations of a fungus, Pycnidiophora dispersa, by ethyl acetate extraction of the whole broth followed by a number of chromatographic steps. Details of the fermentation, taxonomic identification of the producing organism, isolation and biological characterization of these compoundscan be found in the preceding paper in this journal.1}
A series of 2-and 4-quinolones substituted in the hetero-ring have been evaluated using 13C NMR techniques. Substituent effects are discussed as an aid to evaluation of potential tautonnerimtion in the 2-quinolone systems. The observed substituent shifts for systems having a hydroxy function at the 4-position in the 2-quinolones can be explained without implementing the tautomerism to a 4-quinolone.During the course of some synthetic investigations involving the preparation of substituted 2-and 4-quinolones, it became necessary to use 13C NMR for the analysis of the products. A search of the literature for model systems revealed that very little work has been done in this area, other than for the parent compounds and some ring methylated derivatives.' It seemed of interest to extend these studies to include compounds substituted in the hetero ring, such as 1 and 2 shown below.From the data given in Table 1 it can readily be observed that several of the I3C chemical shifts vary over a large range. The C-2 and C-3 chemical shifts, which range over 18ppm and 32ppm, respectively, can be explained on the basis of substituent shifts inherent to the type of substitution involved. The N-CH, and C-4 chemical shifts also show a large range, and in both cases the shifts are to higher field than the parent system. The upfield substituent shift reflects the steric environment of these carbons. Interestingly, the N-CH, resonance seems sensitive to electronic effects, as seen in a comparison of shifts for l c and Id. The remaining carbon chemical shifts are much less affected by substituents at C-2 and C-3, with C-4a and C-6 showing the largest variations. In all, the substituent chemical shifts for 1 appear to be unexceptional and, therefore, should be useful for the analysis of the tautomerism possibilities in the 2-quinolones discussed below.
4-QuinolonesThe chemical shift data are given in Table 1, and the system numbering is shown above. The assignments are relatively straightforward and were made by comparison with the parent compound and the unmethylated material previously assigned in the literature.'
2-Quinolones
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