The Ojima lactam is an organic compound of some importance in the commercial production of Taxol. This lactam was first synthesized by Iwao Ojima.[1] The organic synthesis is an illustration of asymmetric synthesis via a chiral auxiliary.
The reaction centers around an imine - lithium enolate cycloaddition. In order to ensure the correct stereochemistry (the phenyl group and the silyl ether must adopt a cis configuration) in the β-lactam a chiral auxiliary is used in the enolate synthesis. The enolate synthesis starts from glycolic acid. The hydroxyl group is protected by a benzyl group and the carboxylic acid is activated by reaction with thionyl chloride to the acid chloride. The acid chloride reacts with the chiral auxiliary trans-2-phenyl-1-cyclohexanol. The benzyl group is then removed and replaced by a TES silyl ether by reaction with triethylsilyl chloride. Reaction with phenyllithium affords the enolate.
Ojima lactam I
The imine synthesis is a reaction of hexamethyldisilazane with phenyllithium to a strong amide base followed by a condensation reaction with benzaldehyde.
Ojima lactam II
Both imine and enole intermediate join in a cycloaddition reaction followed by an intramolecular nucleophilic acyl substitution of the amine with expulsion of the chiral auxiliary to the cis-lactam. The triethylsilyl group is removed by hydrogen fluoride and the benzoyl group is added in a Schotten-Baumann reaction.
Ojima lactam III
^Iwao Ojima; Ivan Habus; Mangzhu Zhao; Martine Zucco; Young Hoon Park; Chung Ming Sun; Thierry Brigaud (1992). "New and efficient approaches to the semisynthesis of taxol and its C-13 side chain analogs by means of lactam synthon method". Tetrahedron. 48 (34): 6985–7012. doi:10.1016/S0040-4020(01)91210-4.
The Ojimalactam is an organic compound of some importance in the commercial production of Taxol. This lactam was first synthesized by Iwao Ojima. The...
Abitibi-Ouest, in Quebec, Canada Ou Island, an island in Okinawa, Japan Ojimalactam, an organic compound of some importance in the commercial production...
and the Heck reaction. Taxol resulted from the tail addition of the Ojimalactam to alcohol 51, which is baccatin III (the original target molecule of...
method has been successfully applied for the practical synthesis of the Ojimalactam, a key intermediate for the commercial production of paclitaxel (Taxol)...
stage addition of the tail, a process (except for one) based on the Ojimalactam. Holton Taxol total synthesis - year: 1994 - precursor: Patchoulol strategy:...
compound before the addition of the amide tail. As shown in Scheme 7, Ojimalactam 7.1 reacted with alcohol 7.2 with sodium bis(trimethylsilyl)amide as...
envisaged that Taxol (51) could be accessed through tail addition of the Ojimalactam 48 to alcohol 47. Of the four rings of Taxol, the D ring was formed last...
Example of use of trans-2-phenyl-1-cyclohexanol as chiral auxiliary: Ojimalactam Valine as a Chiral auxiliary in the Schöllkopf method Key Chiral Auxiliary...
starting material and for being the only total synthesis not to use the Ojimalactam to create the amide tail. Instead, the tail is created from scratch by...
In common with the other efforts the tail addition is based on the Ojimalactam. The 20 carbon frame is constructed from several pieces: propargyl alcohol...
49 and the benzoate group re-introduced in 50. Tail addition of the Ojimalactam 51 was not disclosed in detail but finally taxol 52 was formed in several...
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