Natural product synthesis via aziridines

Natural products, synthesis via aziridine intermediates, 39, 181 New developments in the chemistry of oxazolones, 21, 175 Nitration of phenyl-substituted heterocycles, 58, 215 Nitrenes, carbenes and, intramolecular reactions of, 28, 231... 

The synthesis of triazoles by 1,3-dipolar cycloaddition between azides and alkynes has been extensively studied recently with numerous synthetic applications in the field of click chemistry. However, the Huisgen cycloaddition between azides 39 and alkenes 40 (Scheme 41.9) although less studied offers interesting opportunities for the stereoselective formation of C N bonds in the context of natural products synthesis. The triazolines 41 thus formed are in fact good precursors of aziridines via ring contraction and expulsion of N2. 

Aziridines represent an important class of building block within synthesis. This structural motif is also embedded within a number of biologically significant natural products, and thus robust and efficient methods for their construction represent an important contribution to the synthetic toolkit. Cordova reported an enantiose-lective aziridination of a,P-unsaturated aldehydes catalysed by diarylprolinol ether 30 using protected hydroxylamine 91 as the nitrogen source (Scheme 38) [150]. The reaction was proposed to proceed via iminium ion formation followed by... 

Quinazolinone annelation of the 0-protected chiral pyrolidinone 74 (derived from L-aspartic acid) forms pyrrolo[2,l-fc]quinazohn-9(lH)-one 75 subsequent desilylation affords (S)-(-)-vasicinone 10, which is identical with the natural /-product (Scheme 16) [212,213]. Asymmetric oxidation of de-oxyvasicinone 11 (via the imine enolate) with either (R)- or (S)-Davis ox-aziridine reagent (lO-camphorsulfonyloxaziridine) [214,215] provides a convenient route to both enantiomers, thus confirming the recently revised stereochemistry of natural vasicinone (Scheme 16) [212,213]. Recently another approaches to optically active pyrrolo[2,l-fo]quinazolinones 10 have been reported by Kamal et al. (lipase-catalyzed resolution) [56], and Argade et aL (asymmetric synthesis from (S)-acetoxysuccinic anhydride) [216]. One-pot synthesis of 11, and related alkaloids has been also developed by utilizing microwave irradiation by Liu et al. [217]. Biogenetically patterned short-step synthesis of pyrroloquinazolinone alkaloids is well established by On-aka [218], and for many other synthesis, see the references cited in these papers. 

A synthesis of the C1-C17 fragment of the cytotoxic natural product carzinophilin (azinomycin B) 193 has been reported. The synthesis proceeds via the known pyrrolidinone 190 converted to the thiolactam 191, then elaborated to intomediate 192 (Scheme 45). The key E alkene stereochemistry is obtained by isomerization of the E/Z mixture of 192 on standing, and the aziridine ring is then introduced using fluoride catalysis. 

Mechanistic approaches to asymmetric aziridine synthesis have been carried out systematically using a variety of p-substituted benzaldehydes (Table 4.16). Two kinds of reaction mechanism, controlled by the nature of the p-substituent of aryl aldehydes, are proposed an S i-like mechanism, via cationic-like transition state for the fragmentation of intermediate adducts to aziridine products (step 2) by intramolecular nucleophihc substitution, when EDG-substituted benzaldehydes are used and an Sielectron-withdrawing group (EWG) substituted benzaldehydes are used [99]. 

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