Preparation of maytansinol
A scaled process of preparing maytansinol, FORMULA II, is provided by reacting a compound of Formula I, wherein R is selected from the group consisting essentially of alkyl, branched alkyl, aryl, alkenyl, alkynyl, as well as substituted variations thereof, with at least one organometallic reagent to produce the compound of Formula II; and, isolating the compound of Formula II.
1. A method of preparing a compound of Formula II
comprising reacting, in a polar aprotic ethereal solvent, a compound of Formula I, wherein R is selected from the group consisting of alkyl, branched alkyl, aryl, alkenyl, alkynyl, as well as substituted carbon or heteroatom containing alkyl, branched alkyl, aryl, alkenyl or alkynyl, with at least one organometallic reagent to produce the compound of Formula II; and, isolating the compound of Formula II.
2. The method according to claim 1 wherein the compound of Formula I is provided from ansamitocins.
3. The method according to claim 2 wherein the compound of Formula I is provided as Ansamitocin P-3 (AP-3).
4. The method according to claim 1 wherein the organometallic reagent is an organomagnesium reagent.
5. The method according to claim 4 wherein the organometallic reagent is selected from the group consisting of methyl magnesium halide, ethyl magnesium halide, propyl magnesium halide, butyl magnesium halide, and hexyl magnesium halide, where the halide is chloride, bromide, or iodide.
6. The method according to claim 5 wherein the organometallic reagent comprises magnesium bromide.
7. The method according to claim 6 wherein the organometallic reagent is methyl magnesium bromide.
8. The method according claim 1 wherein the organometallic reagent is a nucleophilic organometallic reagent.
9. The method according to claim 8 wherein the nucleophilic organometallic reagent is selected from the group-consisting of organocuprate, methyl-lithium, ethyl-lithium, n-butyl-lithium, hexyl-lithium and alkylaluminum reagents.
10. The method according to claim 1 , wherein the polar aprotic ethereal solvent is selected from the group consisting of 1,4-dioxane, diethyl ether, cyclopropylmethyl ether, cyclopentylmethyl ether, dimethoxyethane, methyl tert-butyl ether, diglyme, tetrahydropyran and 2-methyltetrahydrofuran.
11. The method according to claim 9 , wherein the nucleophilic organometallic reagent is trimethylaluminum.