Maytenus ovatus Maytansinoids

Isolation and Structure Proof. The maytansinoids were (lie first ansamacrolides to be found in plants. The term maytansinoids refers to those ansamacrolides related to maytansinc, whereas the term maytansides refers to maytansinoids lacking the ester side chain at C-3 as well as the corresponding elimination products. Maytansine was first isolated from the alcoholic extract of Maytenus ovatus Loes. Several other maytansinoids and maytansides have been isolated from this species. The structure of niaytan-sine was established by x-ray crystallographic analysis, and the structures of the other maytansinoids and maytansides were arrived at by comparative nmr studies using maytansine. The absolute configuration of maytansine is 3(5), 4(5), 5(5), 6(R), 7(5), 10(5), and 2 (5). 

Maytansine (73) was the first example of a benzenoid ansamycin with a Ci5 ansa chain. Maytansine was isolated originally from the higher plant Maytenus ovatus (Celastraceae). Subsequently, antibiotics related to maytansine were isolated from the fermentation broth of Nocardia sp. as well as other higher plants. Compounds belonging to the maytansinoid group possess a 1,3,5-trisubstituted benzene moiety as a chromophore. 

Maytansine (73), the first benzenoid ansa macrolide isolated from the higher plant Maytenus ovatus was obtained as an antileukemic ansa macrolide [119,120]. The cytotoxic action of 73 was reported in a preliminary communication [122]. Several other maytansinoids, such as normaytancyprine (75) [123], 10-epitrewiasine (76) and nortrewiasine (78) [124], were isolated from Putterlickia verrucosa and Trewia nudiflora. The structural requirements for the antileukemic activity of naturally and semisynthetic maytansinoids were reported [120,125]. 

Very few degradative reactions have been described for the maytansinoids, since their structures were assigned from x-ray analysis of a readily prepared derivative (14). Moreover, the amounts of material available have been small, discouraging chemical investigations. The methyl and ethyl ethers (replacing the hydroxyl at C-9) of maytansine were obtained in the course of the initial extractions from Maytenus ovatus (62), and their ready formation suggested the preparation of the 3-bromopropyl ether (6) for structure determination by x-ray analysis. The ethyl ether was reported to lack antileukemic activity, possibly because the carbinol-amide function is blocked (61). 

---