Maytansine 3-bromopropyl ether

Fig. 4. Three-dimensional stereo models of ansamycins and their derivatives A) atropiso-streptovaricin C triacetate cyclic p-bromobenzeneboronate (1), B) rifamycin B p-iodo-anilide (2), C) rifamycin Y p-iodoanilide (3), D) tolypomycinone tri-m-bromobenzoate (5), E) maytansine 3-bromopropyl ether (6), F) geldanamycin. All drawings except that for geldanamycin are from Wang and Paul 148) that for geldanamycin was obtained from Dr. D. J. Duchamp, The Upjohn Company (25)...

The structure and absolute configuration of maytansine (72 R = H) has been established by V-ray crystallographic analysis of its 3-bromopropyl ether [72 R = (CH2)3Br]. °° Maytansine represents the first ansa macrolide-type compound that shows in vivo tumour inhibitory properties. ... 

The crystal and molecular structure and the absolute configuration of maytansine (73) were studied using its 3-bromopropyl ether [121] and the cytotoxicity of 73 [122] was reported. Several other maytansinoids, such as colubrinol (74), normaytancyprine (75) [123], 10-epitrewiasine (76), trewiasine (77) and nortrewiasine (78) [124], were isolated from Putterlickia verrucosa and Trewia nudiflora, respectively, and the structure elucidation, and the structural requirements for antileukemic activity of natural and semisynthetic maytansinoids were reported [120, 125]. As described above, maytansine (73) was isolated initially from a higher plant, although it was evident that the content of this compound was extremely low. 

Maytansine is an alkaloid first isolated from Maytems ovatus (Celastraceae) [1], and maytansine is classified as a benzenoid ansamycin. The structure, including absolute stereochemistry, was determined by x-ray crystallography of its 3-bromopropyl ether derivative [2], and a total synthesis has been achieved [3]. 

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). 

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