Aziridines fragmentation

Actnally, 4-methylene-3-oxa-l-azabicyclo[3.1.0]hexanes represent new heterocyclic systems, in which exocyclic double bond is conjugated with both oxygen atom and the aziridine cycle. The combination of three pharmacologically and synthetically important fragments (aziridine, 1,3-oxazolidine, and vinyl ether) in a one molecnle can impart essentially new, nontypical for each functionality separately, properties to these systems. 

The reaction of carbon atoms with A-unsubstituted aziridines leads to alkenes and hydrogen cyanide (72IA3455), probably via extrusion from the initially formed adduct (285). The fragmentation does not appear to be concerted, although this would be a symmetry-allowed process, since only about half the alkene formed retains the aziridine stereochemistry in the case of cM-2,3-dimethylaziridine. 

Aziridine hydrazides, e.g. (310), undergo an interesting fragmentation reaction which results in ring opening and diimide formation (68JA3592). 

Very recently, the Shipman group have made a further step towards a comprehensive structure/activity profile for noncovalent interactions between azinomycin B and DNA [152]. They synthesized simplified azinomycin analogues 69 and 96-98 (Scheme 11.13), retaining both the epoxide and aziridine alkylating functionalities, with systematically altered substitution on the naphthoate fragment, and analyzed their DNA crosslinking by gel electrophoresis. They found that cross-... 

Figure 11.14 Predicted labeling of the enol and aziridine fragments, via oxaloacetate (99) and threonine (100) for the enol fragment, and via a-ketoglutarate (101) for the aziridine fragment. a) First pass through Krebs cycle, b) Second pass through Krebs cycle, c) Third and subsequent passes through Krebs cycle.

Some fragmentation reactions from cyclopropyl carbenes and aziridine derivatives are as follows ... 

The production of 69 and 70 in this photoreaction is in accord with the operation of mechanistic pathways involving the generation and competitive cleavage of aziridinyl-dicarbinyl biradical 71 (Scheme 12). Thus, the major photoproduct 69 is formed by C—N bond cleavage in 71 (path a). The alternative fragmentation of the C—C bond in 71 affords intermediate 72, which cyclizes yielding aziridine 70 (path b). As such, this represents the first example of a 2-aza-di -rr-methane (2-ADPM) rearrangement that occurs via a three-membered-... 

Mitomycin is an antibiotic isolated from the products of living microorganisms of the family Streptomyces caepitosus and contains quinone, urethane, and aziridine fragments [109-114], and it was later synthesized [115,116]. 

Benzothiazepines can be constructed from substrates of type (376) and an appropriate C—C— N fragment thus, 2,3-dihydro-1,4-benzothiazepin-5-one (377) can be prepared by reaction of (376 R = OH) with aziridine. The reaction of 2-mercaptoaryl ketone (376 R=Ph) with 2-bromoethylamine is a two-stage process intermediate (378) cyclizes in the presence of pyridine to give (379). The reaction of (376 R=OMe) with chloroacetonitrile in the presence of alcohols (R OH) gives (380) (740PP287). 

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