Highly fluorescent and stable 6,7-dimethoxy-2-oxoquinoline-4-carbonitriles (11) were synthesized starting from appropriate 4-hydroxyquinolones 3 via reactive 4-chloroquinolones 8 by using toluenesulfinates as catalysts. In contrast to the well-described 4-trifluoromethyl-substituted analogues 18, N-substituted derivatives 11 fluoresce in water, polar, and apolar solvents in a narrow 430-440-nm window with almost constant quantum yield of 0.5. Equal excitation is possible in the broad double maximum between 385 and 410 nm yield-

Reactions of 2,4‐dichloroquinolines (2a–f) with sodium azide in DMF lead either regioselectively to 4‐azido‐2‐chloroquinolines (3a–f) or with excess of sodium azide and catalysts to 5‐azido‐tetrazolo[1,5‐a]quinolines (4a–f). 2,4‐Dichloroquinolines (2g–i) having electron donating substituents in 3‐position react with sodium azide in DMF to a mixture of 4‐azido‐2‐chloroquinolines (3g–i) and 5‐chlorotetrazolo[1,5‐a]quinolines (5g–i). When the reaction of the 2,4‐dichloroquinolines (2a–i) with sodium azide is carried out in ethanol with addition of methanesulfonic acid, regioselectively 5‐chloro‐tetrazolo[1,5‐a]quinolines (5a–i) are obtained. Structural assignments of 3 and 5 have been carried out by 13C‐NMR spectra, IR spectra and degradation reactions of the azido‐ and tetrazolo group to aminoquinolines (7 and 10) via iminophosphoranes (8 and 9). It could be shown that in 2‐azido/tetrazolo‐quinolines (4 and 5) the tetrazole ring structure is the dominant species.

4‐Azido‐2(1H)‐quinolones 1 are thermolyzed in the presence of carboxylic acids and polyphosphoric acid to yield oxazolo[4,5‐c]quinolones 3. Formation of other possible isomeric ring closure products such as oxazolo[5,4‐c]quinolones 2 or isoxazolo[4,3‐c]quinolones 4 could be excluded by independent syntheses.

Thus, the determination of the percent of IgG1 by itself and/or in combination with conventional markers may provide relevant information regarding the noninvasive detection of early stages of gynecologic carcinoma.

A reactive disulfide bond (SS)* was detected and characterized in IgG of humans, rats and mice by virtue of disulfide interchange with dithionitrobenzoate. (SS)* was found exclusively in human IgG1 and rat IgG2b. In human IgG1 (SS)* was identified as the upper one of the two interheavy bridges in the hinge, where it appears to take part in complement activation. The biological significance of (SS)* in IgG was underlined by the fact that no other serum proteins were found to exhibit a similar reactivity.

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METHODS.Using affinity chromatography, IgG1, IgG2, and total IgG were determined in 36 patients with colorectal carcinoma of different stages and compared 1 Department of Biochemistry, University of with 162 apparently healthy controls. Graz, Graz, Austria. RESULTS.It was found that: 1) the mean values for %IgG1 and %IgG2 of all carci-2 Department of Surgery, University of Graz, noma patients differed significantly from those of the controls; 2) no quantitative Graz, Austria.association was found with tumor stages, and four of five patients with incipient adenocarcinoma within a polyp exhibited the characteristic shift in IgG subclasses; 3 Department of Medical Chemistry, University 3) based on a calculated cutoff, the specificity and sensitivity of %IgG1 to discrimiof Graz, Graz, Austria.nate between controls and carcinoma patients was found to be 88% and 74%, 4 Department of General and Experimental Parespectively; and 4) a quantitative correlation between individual %IgG1 values thology, University of Graz, Graz, Austria.and the probability of correct assignment to carcinoma patients or controls was established.CONCLUSIONS. The significant decrease in %IgG1 accompanied by an increase in %IgG2 in total serum IgG represents an indirect, tissue nonspecific, and early marker of malignant proliferation that distinguishes colorectal carcinoma patients from healthy controls with a specificity of 88% and sensitivity of 74%. T he profile of subclasses within total serum immunoglobulin (Ig)G in healthy persons is tightly regulated to 60 -70% IgG1, 20 -30% IgG2, 5 -8% IgG3, and 0.7 -4% IgG4, independently of absolute serum levels of total IgG ranging between 8 and 18 mg/ml. The authors have previously reported a characteristic shift in the composition of IgG subclasses in close association with malignant tumors of various tis- nign diseases did not show comparable findings, nor was such a dysproteinemia observed in other nonmalignant diseases. With cerReceived July 31, 1996; revision received December 3, 1996; accepted December 23, 1996. tain tumors this phenomenon exhibited diagnostic sensitivities and

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