Synthesis of 1,3-diazaazulene derivatives of colchicinoids and isocolchicinoids via ipso- or tele-substitution-condensation with amidines

Tetrahedron

Volumn 54, Issue 46, 1998, Pages 14059-14064

  Cavazza, Marino ^a   Pietra, Francesco ^b  

^a UNIVERSITY OF PISA   (Italy)

^b UNIVERSITY OF TRENTO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; AMIDINE; AZULENE DERIVATIVE; BENZAMIDINE; COLCHICINE (10 METHOXYCOLCHICIDE); COLCHICINE DERIVATIVE; GUANIDINE; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL STRUCTURE; DRUG STRUCTURE; DRUG SYNTHESIS; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; THIN LAYER CHROMATOGRAPHY;

EID: 0032511942     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(98)00856-4     Document Type: Article

References (12)

1. 1 Brossi, A. J. Med. Chem. 1990, 33, 2311-2319.
2. 2 Cavazza, M.; Pietra, F. J. Chem. Soc., Perkin Trans 1 1995, 2657-2661.
3. 3 Cavazza, M.; Cabrino, R.; Del Cima, F.; Pietra, F. J. Chem. Soc., Perkin Trans 1 1978, 609-612.
4. 4 Reaction rates were only roughly estimated from scattered yield vs. time data but no reaction orders could be measured for heterogeneous systems due to the low solubility of the amidines.
5. 5 Anyway, HR-MS data are far more reliable than elemental analysis for these compounds that tend to occlude solvents of crystallization.
6. 6 Pietra, Acc. Chem. Res. 1979, 12, 132-138.
7. 7 Cavazza, M.; Pietra, F. J. Chem. Soc., Chem. Commun. 1994, 897-898.
8. 8 Cavazza, M.; Pietra, F. Z. Naturforsch. 1996, 5Ib, 1347-1351.
9. 9 9-Alkoxyisocolchicides, like isocolchicine (Scheme 3, X = OMe), can be prepared by diazoalkane alkylation of colchiceine. However, this requires tedious chromatographic separation of 9-alkoxycolchicides from the 10-isomers that are also formed. Therefore, we have devised here a more direct route to 9-alkoxyisocolchicides from the easily available 9-tosyloxyisocolchicide 10 (Staretz, M.E.; Hastie, S.B. J. Org. Chem. 1991, 56, 428-432) via nucleophilic substitution by titanium tetraalkoxides. This reagent has been used to bring about the exchange the alkoxy groups at C-10 in 10-alkoxycolchicides (Kouroupis, P.; Kessler, J.; Hansen, H.-J. Helv. Chim. Acta 1996, 79, 208-212).
10. 9 9-Alkoxyisocolchicides, like isocolchicine (Scheme 3, X = OMe), can be prepared by diazoalkane alkylation of colchiceine. However, this requires tedious chromatographic separation of 9-alkoxycolchicides from the 10-isomers that are also formed. Therefore, we have devised here a more direct route to 9-alkoxyisocolchicides from the easily available 9-tosyloxyisocolchicide 10 (Staretz, M.E.; Hastie, S.B. J. Org. Chem. 1991, 56, 428-432) via nucleophilic substitution by titanium tetraalkoxides. This reagent has been used to bring about the exchange the alkoxy groups at C-10 in 10-alkoxycolchicides (Kouroupis, P.; Kessler, J.; Hansen, H.-J. Helv. Chim. Acta 1996, 79, 208-212).
11. 2 To compare with present condensations, the above reaction has now been run in dry benzene at room temperature, with the same result.
12. 11 Cavazza, M.; Pietra, F. Synth. Commun. 1997, 27, 3405-3413.