Synthesis of β-lactams by transition metal promoted Staudinger reactions: alternative synthetic approaches from transition metal enhanced organocatalysis to in situ, highly reactive intermediate synthesis and catalytic tandem reactions

Abstract

The development of new types of β-lactam antibiotics is a relevant field of contemporary pharmaceutical research. Although many types of antibiotics are available on the market and widely used, β-lactam antibiotics are considered to be one of the best choice as they are highly effective while having reasonable safety profiles. The wide application however has led to the appearance of resistant bacteria suppressing their efficacy. In the last decade fewer and fewer new antibiotics have been launched into the market, however more and more multiresistant germs have appeared posing significant threats especially to patients who are suffering from chronic diseases and have weakened immune systems. The development of new, highly efficient antibiotics is now direly needed. One of the options to accelerate β-lactam antibiotic research is the development of alternative robust, convenient, versatile and cheap synthetic procedures in which the β-lactam molecules can be easily synthesized with the desired diastereoselectivity. The most general way to introduce diastereoselectivity in the chemical reactions is the application of chiral catalyst systems. While there are several systems for the synthesis of β-lactams the transition metal assisted Staudinger reaction – [2 + 2] cycloaddition between a ketene and an imine – remained the most simple and most versatile methodology. The motivation behind this brief review is to draw the chemical community's attention to the relevance and applicability of transition metal promoted Staudinger reactions in β-lactam based antibiotic development. This article summarizes the most relevant pioneer works completed on this field in order to open new ideas for the forthcoming organometallic systems based bioactive material development.