synthesis and modifications of phosphinic dipeptide analogues次膦二肽类似物的合成和修改.pdfVIP

Molecules 2012, 17, 13530-13568; doi:10.3390/molecules171113530 OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Review Synthesis and Modifications of Phosphinic Dipeptide Analogues Artur Mucha Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland; E-Mail: artur.mucha@pwr.wroc.pl; Tel.: +48-71-320-3446; Fax: +48-71-320-2427 Received: 17 October 2012; in revised form: 9 November 2012 / Accepted: 12 November 2012 / Published: 15 November 2012 Abstract: Pseudopeptides containing the phosphinate moiety (-P(O)(OH)CH -) have been 2 studied extensively, mainly as transition state analogue inhibitors of metalloproteases. The key synthetic aspect of their chemistry is construction of phosphinic dipeptide derivatives bearing appropriate side-chain substituents. Typically, this synthesis involves a multistep preparation of two individual building blocks, which are combined in the final step. As this methodology does not allow simple variation of the side-chain structure, many efforts have been dedicated to the development of alternative approaches. Recent achievements in this field are summarized in this review. Improved methods for the formation of the phosphinic peptide backbone, including stereoselective and multicomponent reactions, are presented. Parallel modifications leading to the structurally diversified substituents are also described.