Maytansinoids Maytansinol

Several semisynthetic maytansinoids have been prepared by acylating the C-3 hydroxyl group of maytansinol. Some of these derivatives have antiprotozoal and antitumor activity similat to maytansine (104) and ansamitocin P-3 (127) (52,254). 3-Epimaytansinoids have been synthesized and were not biologically active (255). 

Biological Activity. The maytansinoids possess antitumor activity, particulady against P 388 lymphocytic leukemia, B 16 melanocarcinoma, and Lewis lung carcinoma. A number of semisynthetic esters of maytansinol have been prepared and exhibit good antileukemic activity (52,255). The maytansides lack antitumor activity, indicating that the ester at C-3 is a requirement for activity (50,52). The carbinolamide also appears to be necessary for... 

Recently Kupchan et al.219 isolated two Maytansinoids Maytanacine and Maytansinol. They differ from the previously described Maytansinoids by different substituents at C-3, both being without an amino acid residue at that position. Semisynthetic Maytansinoids have also been prepared by esterification of the 3-OH group of Maytansinol. 

Oxazines without a nitro group have also been suggested as antitumor compounds.56 Maytansinoids possess antileukemic and antitumor activity275"279,288 with the exception of Maytansinol.279... 

Maytansinoids continue to be isolated or synthesized in attempts to improve anti-tumour activity, and a review of the results of their preclinical and clinical testing has appeared.31 A variety of maytansinol esters has been prepared by... 

This method was employed by Meyers et al. [142] in the synthesis of ( )-maytansinol 233), the common precursor to the ansa macrocyclic antitumor agents, maytansinoids, to construct the macrocycle. As shown in Scheme 77, the cyclization of amide ester 231 to 232 was accomplished in 58% yield by using 4 equiv of lithium(hexamethylsilyl mide at — 78 °C for 4 h. 

Two new maytansinoids, maytanacine (228) and maytansinol (229), were isolated from the alcoholic extract of the stem of Putterlickia verrucosa Szyszyl. [260], the richest reported source of maytansine (218) and related antileukemic esters. Maytanacine (228), which exhibited... 

The coupling between the aliphatic and aromatic segments (75 + 77) yielded 78. The geometry of the olefin was a mixture of E and Z. The allylic acetal in 78 was the part most reactive to acid, and it was hydrolyzed with dil. acetic acid to the unsaturated aldehyde 79 (Scheme 10). This compound was the key intermediate for the syntheses of all the maytansinoids such as N-methylmaysenine, maysine [13] and maytansinol [14]. 

These alkaloids were named as ansamitocins, and the chemical structures of ansamitocins P-1,2, 3, 3, and 4 are shown in the figure. These alkaloids are based on ansamitocin P-0, a common parent skeleton, by a reductive hydrolysis of ansamitocins P-1,2,3,3, and 4 using LiAlH4. Ansamitocin P-0 corresponds to maytansinol, which is the parent skeleton of the above-mentioned maytansine. On the other hand, it was found that ansamitocins P-1 and P-2 isolated from Maytenus plants corresponded to maytanacine and maytansinol propionate, respectively [7].The alkaloids possessing the maytansinol (ansamitocin P-0) skeleton are also referred to as maytansinoids. The synthesis of maytansinol (ansamitocin P-0) as a racemic mixture has been reported [8]. 

Kupchan SM, Branfman AR, Sneden AT, Verma AK et al. 1975 Novel maytansinoids. Naturally occurring and synthetic antileukemic esters of maytansinol. J Am Chem Soc 97 5294... 

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