Colchicine derivatives

Lettre and Fernholz have tested a series of colchicine derivatives, including a group of alkylcolchiceines, on experimentally induced tumours all proved to be less potent than the parent alkaloid. A -Acetyl-j3-p-anisyl-y-(3 4 5-trimethoxyphenyl)-propylamine,... 

Seitz and colleagues108 made 10-ethylcolchicide (138), a colchicine derivative, react with several dienophiles. The reaction of 138 with dimethyl acetylenedicarboxylate (57) afforded a single Diels-Alder adduct (139) which underwent a consecutive [3 + 2] cycloaddition with another equivalent of dimethyl acetylenedicarboxylate to give 140. The formal elimination of C2H6 afforded 141, whereas fragmentation led to 142 (equation 41). 

Alkaloids with ExocycJie Nitrogen Colchicine Derivatives... 

Small molecules modulating microtubule assembly have played major roles as tools in microtubule research, in a manner closely related to their chemotherapeutic interest [1], Tubulin was first purified in the last century as the colchicine-binding protein proposed to be the subunit of cellular microtubules [2], More recently, a colchicine derivative was employed to help crystallization and determine the structure of tubulin by X-ray diffraction [3], The colchicine, vinblastine [4] and paclitaxel [5] sites are main drug binding sites of tubulin, to which many other substances bind. The discovery of microtubule stabilization by paclitaxel [6] prompted its clinical development [7] and a burst of research on new MSAs, as well as the generalized use of paclitaxel or docetaxel as convenient reagents to assemble (see Fig. 1), stabilize or detect microtubules in the laboratory. One example is the development... 

The colchicine binding site in tubulin was initially identified using a colchicine derivative bearing a sulfhydryl group, permitting unambiguous orientation of the ligand in the electron density map [15]. We have also determined the structure of... 

A series of dibenzazocines was designed for application in the synthesis of homochiral polyamide polymers <1998TA3497>. Bis-oxo-tetrahydrodibenzazocines showed picomolar to nanomolar inhibition of 17/ -hydroxysteroid dehydrogenase of type 3 <2006BML1532>. Colchicine derivatives that contain the dibenzazocine moiety have been studied for their biological properties <2000BMC557>. 

No conclusions as to any structure-activity relationship can be made in the field of tumour inhibitory alkaloids, in spite of the enormous amount of work that has been carried out. Structures and origin of alkaloids vary widely and it does not seem to be the prerogative of a few plant families to elaborate tumour inhibiting alkaloids. Two Catharanthus alkaloids and a few colchicine derivatives have become commercial products, but they certainly do not represent a final solution to the enormously complicated cancer problem. 

The first compound of the taxanes series, paclitaxel (Taxol), was isolated from the bark of the Western yew tree in 1971. It and its congenic, the semisynthetic docetaxel (Taxotere), exhibit unique pharmacological actions as inhibitors of mitosis, differing from the vinca alkaloids and colchicine derivatives in that they bind to a different site on P-tubulin and promote rather than inhibit microtubule formation. The drugs have a central role in the therapy of ovarian, breast, lung, esophageal, bladder, and head and neck cancers. 

Structural evidence for a series of colchicine derivatives (113 R = alkyl) has been provided by i.r. spectroscopy. Another series of derivatives, prepared by the... 

ORD-studies conducted on colchicine derivatives, colchinols, and ]8-and y-lumicolchicine (Table II) have clarified some of the stereochemical aspects of these molecules (28). Colchinol (XIX) and its derivatives are essentially bridged and skewed biphenyls. They show a single strong negative Cotton effect at 260 mp which implies an S-configuration (XX), also indicated in the X-ray analysis of colchicine (XXI). 

A number of colchicine derivatives have been analyzed by mass spectroscopy under conditions which allowed clear fragmentation patterns to be observed in the high mass region 40). 

Abu Zarga et al. [33] assigned structure 21 to the alkaloid suhailamine without recognising that this is also the structure of the well known colchicine derivative allocolchicine. Since the spectral data derived from suhailamine do not match those recorded for allocolchicine, the structure proposed for the former compound is presumed to be incorrect. 

Camptothecin Derivatives Polyphenolic Compounds and Sesquiterpene Lactones Antitumor Quassinoids Flavonoid Derivatives Colchicine Derivatives Quinone Derivatives... 

The antileukaemic activity of colchicine derivatives"" and their effects on RNA synthesis,on intestinal disaccharidase activity," " and on the secretion of parathyroid hormone" have been studied. 

Leblanc and Fagnou have presented a synthesis of a colchicine derivative, in which one component of the intramolecular cross-coupling does not need to be activated at the specific and desired carbon atom (Scheme 25). The natural... 

Like other alkaloids, supply of colchicine from traditional sources is limited either due to the gradual decreasing condition of plant sources or due to trace amounts of compounds present in the plants. Therefore, several alternative strategies have been adapted to increase the production of colchicine and colchicine derivatives. 

A number of analogous cases are known in the colchicine series, in which a similar type of structure is believed to exist. Scott and Tarbell [25] have found a strong 1620—1612 cm" band in six colchicine derivatives which they attribute to the carbonyl group, and this is confirmed to some extent by the fact that this band vanishes in tetrahydrocolchicine and is replaced by a 1710 cm band which corresponds to the normal carbonyl frequency of a seven-membered saturated ring. A similar band near 1610 cm" has been found by Nicholls and Tarbell [42] and by Fabian, Delaroff, Poirier and Legrand [165] in a series of benzotropolones and in colchicines [79]. 

SCHEME 12.48 Key steps in Tobinaga s and Evans synthesis of colchicine derivatives. 

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