Aziridine moieties

It is likely that the madurastatins are biosynthesized on a nonribosomal peptide synthetase, from salicylic acid as the starter acid. L-Serine is probably the precursor to the aziridine moiety, with epimerization occurring on the enzyme-bound amino acid as found for other nonribosomal peptides, with aziridine formation occurring at a late stage. Compounds 120 and 123 could therefore be biosynthetic precursors to 119 and 122, respectively. 

The research groups of Mariano and West developed a photoinduced electrocydi-zation/nucleophilic addition sequence. Thus, irradiation of N-alkylpyridinium perchlorates as 5-19 in an aqueous solution led to the aziridine cations 5-20, which react in a nucleophilic addition with OH to give the isolable azabicyclo[3.1.0]hex-2-enols 5-21. These can be further transformed by a nucleophilic ring-opening of the aziridine moiety under acidic conditions to lead to useful unsymmetrically trans,trans-trisubstituted cyclopentenes 5-22 (Scheme 5.5) [10]. 

In this molecule only the bond between the steroid skeleton and the aziridine moiety can rotate freely. A molecular mechanics conformational analysis resulted in two low energy conformations (Fig. 9.4, see p. 264), both of which had almost identical potential energy, as calculated in the Tripos force field [10]. 

Unfortunately, A-(9-fluorenylmethoxycarbonyl)aziridine-2-carboxylic acid cannot be used in peptide synthesis, since N-deprotection of the respective peptides with secondary amines leads to oxazoline or dehydroamino acid side products. Similarly, N-(tert-butoxy-carbonyl)aziridine-2-carboxylic acid is inappropriate due to the instability of the aziridine moiety to TFA treatment. Attempts to convert A-tritylaziridine-2-carboxylic acid into homogenous and stable active esters as useful intermediates in peptide synthesis leads to positive results only in the case of the pentafluorophenyl ester. 47 Consequently, this active ester seems to be the method of choice for acylating peptides. The related Abhydroxysuc-cinimide and A-3-hydroxy-4-oxo-3,4-dihydro-l,2,3-benzotriazine ester could not be isolated in pure form and have therefore been used as crude products. 47 Access to 2-carbonylazir-idine peptides is also possible by carbodiimide-mediated coupling. Additionally, alkylamides of A-tritylaziridine-2-carboxylic acid are prepared by the azide method,1 5 yet this method fails in peptide coupling steps. 85 ... 

Fusion of an aziridine moiety in a structure which cannot open in a conrotatory fashion inhibits the formation of an azomethine ylid by the thermal process. An example of such a compound is 77 which failed to give cycloadditions up to 180°.50 Oida and Ohki80 irradiated a related compound (78) in dioxane at 15° for 2 hours in the presence of 2 equivalents of DMAD. They obtained 4% of compound 79 and 36% of the isomeric 80 mild alkaline hydrolysis of 79 gave the amorphous 82,... 

Diphenylacetylene reacted with both complexes by insertion into the aziridine moiety as shown for the eg complex in Scheme 8.11. Both reactions were inhibited by addition of external PMe3 showing that the dissociation of PMe3 was required for both, even though the eg complex is electronically unsaturated and may have been expected to react by an associative mechanism. 

The nature of the /V-subsiiiuen1 of the aziridine moiety has been found to play an important role in the deprotonation reaction of oxazolinylaziridines.16 An electron-donating group appeared to be the /V-subsiilucnt of choice when the oxazoline moiety has a cis relationship with respect to the proton to be removed. The high stability of the resulting aziridinyllithium may be due to the coordinative effect of the oxazoline ring. 

As with the epoxides, there are two broad categories of synthetic approach to the aziridine moiety (a) addition of a nitrogen center onto an existing alkene or (b) addition of a carbon center onto an imine. The reader is directed to an excellent review of both approaches within the context of enantioselective catalytic aziridination <03CR2905>. Illustrative additional offerings from the past year s literature are also included below. 

Type I aziridines can be prepared via photolysis of functionalized pyridinium ions. Mariano and co-workers have shown that irradiation of pyridinium ion 40 via a 450 W Hanovia lamp with Vycor filter will induce a ring contraction to produce a fused-bicyclic aziridine moiety 41 (Equation 16) <1996JOC4439>. The azabicyclo[3.1.0]hexane prepared through this method can rapidly experience nucleophilic opening to produce an amine-substituted cyclo-pentene. 

N-Alkylation. Silver triflate is essential for an intramolecular alkylation of oxazole that contains an aziridine moiety. A 1,3-dipolar cycloaddition is triggered henceforth. 

In the dinitrobenzenecarboxamide, CB1954 or the quinones AZQ/BZQ (Figure 1, 12, 1 or 2 respectively), the aziridine moiety is deactivated by the electron-withdrawing nitro substituents or the electron-deficient quinone system respectively. However, on reduction the p Ta of the aziridine nitrogen increases, activating the site towards reaction with nucleophiles. 

Azicemicins 1, which consist of a tetracyclic angucycline core structure and a unique aziridine moiety at the C-3 position, were isolated from Kibdelosporangium sp. MJ126-NF4 (formerly known as Amicolatopsis 5/ .[l] and showed antimicrobial... 

Three-membered nitrogen-containing heterocycles (aziridines) have attracted the attention of chemists due to their association with a broad spectrum of biological activity. Many natural products possessing an aziridine moiety have been shown to have high biological activity, such as mytomycins, together with porfiromycin and... 

In 2010, chiral tridentate ligand 25, containing two stereogenic centres, one located on the sulfinyl sulfur atom and the other on the carbon atom in the aziridine moiety, was found by Lesniak and Kielbasinski to be a very efficient nickel ligand for the enantioselective conjugate addition of diethylzinc to chalcones as well as cyclohex-2-enone (Scheme 2.24). The... 

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