2- Imino cyclic ethers synthesis

The discovery of the N-nitroguanidine dinotefiiran (4, 2002, Mitsui Chemicals) [58, 59], resulted from the idea of incorporating an N-nitro-imino group into the ACh structure as lead compound [60]. After synthesis of neonicotinoids containing a N-(3-methoxy-propyl) moiety (hydrogen acceptor site) the investigation of cyclic ether groups led to the discovery of the novel THF moiety, which shows a more than ten-fold increase of insecticidal activity. 

Some particularities of the extraction of ions from an aqueous organic phase, and of the phase catalyzed polyetherification will be summarized. These will represent the fundamentals of our work on the synthesis of some novel classes of functional polymers and sequential copolymers. Examples will be provided for the synthesis of functional polymers containing only cyclic imino ethers or both cyclic imino ethers as well as their own cationic initiator attached to the same polymer backbone ABA triblock copolymers and (AB)n alternating block copolymers and a novel class of main chain thermotropic liquid crystalline polymers containing functional chain ends, i.e., polyethers. 

Three major topics of research which are based on phase transfer catalyzed reactions will be presented with examples. These refer to the synthesis of functional polymers containing functional groups (i.e., cyclic imino ethers) sensitive both to electrophilic and nucleophilic reagents a novel method for the preparation of regular, segmented, ABA triblock and (A-B)n alternating block copolymers, and the development of a novel class of main chain thermotropic liquid-crystalline polymers, i.e., polyethers. 

MacrocycBc lactams. Two key steps in a synthesis of the polyamine alkaloid dihydroperiphylline (4) involve ring expansion of the cyclic imino ether 1 by reaction with the /3-lactam 2 to form 3. Sodium cyanoborohydride in acetic acid reduces 3 in high yield to 4, probably by way of intermediates a and b.2... 

The first stereoselective total synthesis of AI-77B, a gastroprotective substance, was accomplished by Y. Hamada and co-workers. In the final stages of the synthetic effort, the intramolecular Pinner reaction was utilized to convert the cyano group into the corresponding carboxylic acid. The nitrile substrate was dissolved in 5% HCI in methanol, and excess trimethyl orthoformate was added at 5 °C and the reaction mixture was stirred at this temperature for almost two days. Next, the cyclic imino ether hydrochloride salt was treated with water at room temperature followed by basic hydrolysis. Finally, the pH was adjusted with HCI to obtain the natural product. 

C-7 Side-Chain Cleavage. 7-ACA (1), the key intermediate for the synthesis of a large number of the clinical cephalosporins, cannot be made by fermentation, nor can it be readily obtained by enzymatic removal (187) of the aminoadipic acid side chain from cephalosporin C. Because substantial quantities of 7-ACA are used, an efficient method for the chemical cleavage of the acyl side chain of cephalosporin C was sought. The first efficient method involved diazotization using nitrosyl chloride, followed by hydrolysis or alcoholysis, and gave 7-ACA in 50% yield (22,23,87,188). The reaction proceeds via the formation of the cyclic imino ether (57) which is easily hydrolyzed under very mild conditions. 

The reaction of 11 with tosyl chlorides gave imino ether (36). The reduction of 36 yielded 9-deoxo-9a-aza-9a-homo-EM A (37). The synthesis of its N-, O-acyl, and A,0-diacyl azalide derivatives, their 11, 12-cyclic carbonates, and their in vitro antimicrobial activities were studied, but 9a-N monoacyl (acetyl, propionyl) compounds exhibited in vitro activity 10 to 50 times lower than that of 37 [26]. 

Linear poly(n-propylenimine) (PnPI) was first synthesized by the alkaline hydrolysis of poly(2-oxazine)s. This synthesis of poly(2-oxazine)s is analogous to the polymerization of 2-oxazolines, albeit the polymerization rate constants are approximately four times slower for the six-membered ring 2-oxazine monomers due to less ring tension and higher steric hindrance during polymerization. In theory, other PHAIs can also be prepared by hydrolysis of poly(cyclic imino ether)s, but this has not been reported so far. For example, poly( -butylenimine) may be synthesized by hydrolysis of poly(oxazepine)s, although such polymers are difficult to prepare, and poly(tert-butylenimine) may be synthesized by hydrolysis of the poly(cyclic imino ether) resulting from commercially available 2,5,5-trimethyl-2-oxazoline. 

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