Podophyllotoxin derivatives. 3. The remaining diastereo C-4 alcohols and ketone of the L series

Abstract

J = 9 Hz), 6.41 (s, l), 7.24-7.84 (m, 7), and 8.24 (m, 1); HRMS mle (re1 intensity) found 558.21118 (100) [calcd for C30H30N407, 558.21145 (M+)].Oxidation of Deoxytryptoquivaline (3). To a stirred solution of deoxytryptoquivaline (3, 16.7 mg, 0.032 mmol) in dichloromethane (5 ml) at room temperature was added m-chloroperbenzoic acid (m-CPBA, 6.3 mg, 0.037 mmol). The reaction mixture was diluted with dichloromethane (20 ml) after 15 min, and washed with dilute aqueous NaHCOs. The organic layer was dried (anhydrous Na*SO*), evaporated in vacuo, and chromatographed (HPLC, 3% 2-propanol in hexane as solvent) to give tryptoquivaline (1,12.6 mg, 73% yield), identical with authentic material.Oxidation of Deoxytryptoquivalone (8). Deoxynortryptoquivalone (8,19.6 mg, 0.042 mmol) was oxidized with m-CPBA (8.2 mg, 0.048 mmol) to give, after workup and chromatography (HPLC, 3% 2-propanol in hexane), nortryptoquivalone (7, 12.6 mg, 62% yield), identical with authentic material.Oxidation of Deoxynortryptoquivaline (4). Deoxynortryptoquivaline (4,38.4 mg, 0.074 mmol) was oxidized with m-CPBA (14.2 mg, 0.082 mmol) to give, after workup and chromatography (HPLC, 5% 2-propanol in hexane), nortryptoquivaline (2,34.3 mg, 86.6% yield) identical with authentic material. . Am.Chem. SOC.. 97. 663 (1975).In ref 3 the second metabolite was called tryptoquivalone. Following a request by Professor Mikio Yamazaki we have changed its name to nortryptoquivalone.Org. Chem., 36, 1143 (1971). The fungus was later shown to be A. clavatus rather than A. glaucus as stated in that paper. We are indebted to Dr. Dorothy Fennell. USDA Fermentation Laboratory, Peoria, Ill., for this identification.The absolute configuration of the tryptoquivalines could not be determined by the x-ray method and remains unknown. We wish to thank Professor M. Yamazaki for having compared this metabolite with his norisotryptoquivaline.The preparation of L-isopodophyllotoxin ( 5 ) , L-isopicropodophyllin (7), and 1,-isopodophyllotoxone (12) is described. With these compounds the eight possible diastereomeric C-4 alcohols (toxins) and four possible C-4 ketones of the L series2 are all known. Alcohol 5 instead of its epimer 6 was obtained by sodium borohydride reduction of 12 contrary to predictions based on previously reported reduction of DL-12. USPHS Grant CA-11507. W e are indebted t o Mr. Lew Cary of Stanford Research Institute (XL-100) and Dr. Richard Sprecher of Memphis State University (CFT-20) for NMR help. Mass spectral determinations were performed by the mass spectrometry laboratory, University of Tennessee. . Dr. Schreier, who reversed the assignment of Configuration at C4 of M-iS0-and epiisopodophyllotoxin on the basis of NMR studies on the epimeric acetates, had obtained the epimeric alcohols through reactions involving the synthetic DLdihydroxy acids. He did not have access to the Gensler DL-epiisopdophyllotoxin obtained by reduction of the ketone for a direct comparison (private communication from Dr. E. Schreier).

Quantitation of Aryltetralin Lignans in Plant Parts and among Different Populations of Podophyllum peltatum by Reversed-Phase High-Performance Liquid Chromatography

“…c 0 means no detectable peak was present at retention volume of compound. Acetylpodophyllotoxin (8) was chosen as an internal standard because of its structural similarity to the lignans of interest and the ease of synthesis from podophyllotoxin by acetylation of its hydroxyl group using the procedure described by Aiyar and Chang 11 and its elution in a region of the chromatogram devoid of other peaks using the cited methodology 5 (Figure 2). HPLC Analysis.…”

Laser flash photolysis and pulse radiolysis study on chemical activity of VP-16 and podophyllotoxin

“…Though Wessely had studied PPT in the twenties and thirties of the 20th century, eight diastereomers of PPT were not found before the seventies [1,2] . Eight diastereomers have different antitumor activities in clinical trials and toxin side effects.…”