Colchicine amide

Iphigenia indica Bak. (Syn. Tulipa edulis) Shan Ci Kodfghvb (aerial part) Colchicine, colchicine amide, N-formyl-N-deacetylcolchine, comigerine, P-lumicolchicine.50 Antitumor activity against hepatoma, lymphosarcoma. 

Hydrolysis reactions are illustrated by the deacylation of colchicine (10) (amide hydrolysis), olivomycin A (29), Rifamycin B (46) or thymoxamine (52) (ester hydrolysis). The reduction of pentoxyfylline (32), zearalenone (56) or warfarin (65) are examples of the common reduction of keto groups, generally affording, with a high stereospecificity, one of the alcohol stereoisomers. 

The synthesis of five-, six-, and seven-membcrcd cyclic esters or amides uses intramolecular condensations under the same reaction conditions as described for intermolecular reactions. Yields are generally excellent. An example from the colchicine synthesis of E.E. van Ta-melen (1961) is given below. The synthesis of macrocyclic lactones (macrolides) and lactams (/ > 8), however, which are of considerable biochemical and pharmacological interest, poses additional problems because of competing intermolecular polymerization reactions (see p. 246ff.). Inconveniently high dilution, which would be necessary to circumvent this side-... 

The availability of ketone 68 made possible for the first time the introduction of an amide group at C-5 instead of C-7, as found in natural colchicine (1) and N-acetylcolchinyl methyl ether (58), and to study the effects of this modification on biological activity. The synthesis of the... 

Colchicine is built from an aromatic ring with three methoxy groups, a 7-membered ring, to which is bound an acetylated aminogroup and a tropolone-ring with a methoxy group. Since the nitrogen is amide-bound, colchicine lacks the properties of a base. Demecolchine is N-desacetyl-N-methylcolchicine. 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antip3rrine, atenolol, atropine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorcyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimeti-dine, cisapride, clomipramine, clonazepam, clonidine, clozapine, coceune, colchicine, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvox-amine, furosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydroxychloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, levorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol. 

Pharmacology V., together with vincristine and the semisynthetic vindesine (deacetyl-V.-23-amide), is now established in modem cytostatic therapy (i.v.). It acts in the same was as colchicine (see phenethyltetra-hydroisoquinoline alkaloids) as an inhibitor of mitosis and arrests the metaphase by binding to microtubular proteins. In addition, V. inhibits DNA polymerase and thus also DNA biosynthesis. In combination with other cytostatic agents it is used in therapy for (non)-Hodgkin s lymphomas, testicular, breast, and lung cancer. ... 

Alkaloids are not limited to those natural products which are basic in character. For example, colchicine isolated from Colchicum autumnale (Ldiaceae) and used for the treatment of gout, etc. is not basic because the nitrogen atom in the molecule is present in a neutral amide group. However, the biosynthetic precursor of colchicine is autumnaline, a typical, basic phenethylisoquinoline alkaloid. Therefore any compound derived from such an intermediate should be classified as an alkaloid. 

The amide nitrogen of colchicine is not basic, and some have argued that colchicine is not a true alkaloid. However, as the precursors and the pathway leading to this compound are typical for those of alkaloids, colchicine is considered an alkaloid for present purposes. Although this compound is the best known of the group, more than 30 other tropolonic alkaloids occur in Colchicum autumnale and related plants (Capraro and Brossi, 1984). The physical constants and spectral data of colchicine and related alkaloids have been tabulated (Tojo, 1989). 

AMIDES AND IMIDES Narciclasine Anthramycin Colchicine Colcemid Showdomycin... 

Now let s take a little side journey into the field of alkaloid synthesis. Alkaloids are loosely defined as natural products that contain a basic nitrogen. Some peptides that contain basic nitrogen (lysine and imidazole residues for example) are not classifed as alkaloids, and some amides that do not contain basic nitrogen (colchicine for example) have been called alkaloids, and that is why I use the phrase loosely defined .I have already mentioned that the pyrrolizidine alkaloids are popular synthetic targets and thus, at this point we will examine a few other approaches to these natural products. 

Figure 6.11), pterins and ommachromes, could be included under this heading, while some neutral plant amides like colchicine are always considered among alkaloids. 

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