¹³C‐ and ¹H‐NMR. Assignments for colchicine derivatives

Abstract

SummaryThe I3C-NMR. spectra of a number of colchicine derivatives are given comprising examples of the normal series (4+10), is0 series (11416) and colchiceine series (17), which were either reported in the literature or obtained by partial synthesis or degradation reactions. The I3C-NMR. assignments were made by comparisons with known compounds and selective single-frequency offresonance decoupling experiments. Selective proton decoupling experiments have also allowed assignments of the H-C(l1) and H-C(12) protons of the is0 and colchiceine series.In a recent publication, the results of a study of the microbial transformation of colchicine (1) were reported [l]. With the aid of the proton-coupled I3C-NMR. data, selective single-frequency off-resonance decoupling experiments and by comparison of the data with those of 1 and its hydrolysis products 10-0-demethylcolchicine (colchiceine, 18) and trimethylcolchicinic acid (19), the correct structure to the metabolites obtained, 2-0-demethylcolchicine (2) and 3-0-demethylcolchicine (3) was assigned.We have now examined the 13C-NMR. spectra of other colchicine derivatives comprising examples from the normal series (4 + lo), is0 series (11 + 16) and colchiceine series (17). The I3C-NMR. spectra offer an excellent way to distinguish between derivatives of each series. These compounds are natural products (eg. 2,3, 6, 7) [2], or obtained by partial synthesis (e.g. 8, 9, 11-15, 17) [3-71, or by degradations (e.g. 4, 5, 10, 16, 18, 19) [8-11]9, and have recently been prepared again in connection with another project [7].1-0-Demethylcolchicine (4) was reported to be a microbial metabolite of colchicine (1) [ 121, although only 2-0-demethylcolchicine (2) and 3-0-demethylcolchicine (3) were identified as microbial metabolites using the fermentation I )The isomeric 0-methyl ethers 10 and 16 were obtained by methylation of Woodwarcfs dehydrodeacetylaminocolchiceine, an intermediate in Eschenmoser's total synthesis of colchicine (1) [ 1 I] with CH2N2. The position of the double bond in ring B of 10 and 16 is not firmly established and may well have to be assigned to the 5,6-position.

The importance of the phenyl‐tropolone ‘aS’ configuration in colchicine's binding to tubulin

“…Unnatural (+)-(7R)-colchicine was prepared as in [7]. Deacetamidocolchicine was made by catalytic reduction (Pd/C in ethyl acetate) of deacetamido-5, 6-dehydrocolchicine, prepared according to [8]. Deacetamidocolchicine, thus prepared, showed chemical and physical properties identical with material obtained by total synthesis [9].…”

From Colchicine and Some of Its Derivatives to 1,2,3,9,10‐Pentamethoxybenzo[a]heptalenes

“…5,6-and4,7-Didehydro-7-deacetumidocolchiceine (5b and 5a, resp. ; cf [I 1 h] [34] [35]). Iodide 4 (5.08 g, 9.9 mmol) was dissoleved in 2N NaOH (25 ml) and ethyleneglycol(50 ml).…”

“…Indeed, Brossi and coworkers [34] (cf. [35]) showed later by 'H-decoupling experiments of Sband of the corresponding 9-and 10-O-methyl derivatives 7a and 7b (see Scheme 2) that the double bond is in the 5,6-position.…”

Synthesis of colchifoline from deacetylcolchiceine

“…The chifoline (5) and the iso structure of isocolchifoline first eluted material was identical with colchifoline (6) were evident from a comparison of their IH nmr (5), a minor contaminant of commercial colchicine spectra (aromatic protons) with those of reference (1). The second compound, obtained in at least substances (3,4) reported recently (6)(7)(8). Mass equal amounts, was assigned the structure of spectra of colchifoline (5) and isocolchifoline (6) isocolchifoline (6).…”

“…A mixture of 1 and 2 was obtained from deacetylcolchiceine (8) by the procedure of Raffauf HCl into colchifoleine (9), glycolyl a h~d r o x~a c e t~l a t i n g illustrated with the same arrangements of the oxyagent, was prepared glycolic acid by treat-gen functionalities in ring C as in colchiceine (10) ment with trifluoroacetic anhydride and treatment of the acid with refluxing thionyl chloride in the (5). form of a colorless liquid (see Experimental).…”