What general uses do beta-lactam functional groups have?

Question

I am currently working on a mechanistic study that deals with stereoselective $\beta$-lactam formation. I am well aware that there is a class of antibiotics, that involve this particular functional group. However, the wikipedia article of this compound class does not offer very much to continue, apart from the antibiotics.

Are there any other uses of the $\beta$-lactam moiety in general, apart from drug design?

I would like to be able to view my research in a broader scope. Since my part is more focussed on the reaction mechanism of the synthesis, I have not been too much concerned about the main purpose of this particular functional group, yet. This is of course apart from the obvious drug design process. For me this is just a question of interest.

As I am resurrecting this question, I am in particular looking for some interesting publications about the above mentioned question. However, I am willing to recognise, that the most common use is in drug design. If someone from this area of expertise could provide a source as a starting point for more research in this area.

Answer 1

β-lactams, also known as 2-azetidinones, have experienced a resurgence of interest in the last decade or so, with a number of new applications being exploited. Of course, antibiotic activity is well-known, but I hope you don't limit your acceptance of drug design just to this class of chemical.

β-Lactams have found use in a number of fields of medical application, inlcuding gene activation, enzyme inhibition and cholesterol absorption inhibition, and recently there has been growing interest in the use of these molecules as synthetic templates for accessing other target moelcules.

There are lots of sources of references if you go digging, but some key reviews that may interest you include:

• TETRAHEDRON Volume 56, Issue 31, Pages 5553-5742 (July 2000). The entire issue is concerned with developments in β-lactam chemistry;

• EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY Volume 45, Issue 12, Pages 5541-5560 (DEC 2010) "2-Azetidinone - A new profile of various pharmacological activities" gives some very good insights into new medical applications of this class of compound, including anticancer, antiparkinson, antidiabetic, antiinflammatory activities. I think they can also do the washing up and buy your groceries.

• TETRAHEDRON Volume 59, Issue 39, Pages 7631-7649 (Sep 2003) "Recent progress in the synthesis and chemistry of azetidinones" gives a pretty good summary of synthetic approaches to these molecules.

• Alcaide and Almendros do a lot of work using 2-azetidones as reactive synthons in catalytic cyclisations. A recent review by them is

  ACCOUNTS OF CHEMICAL RESEARCH Volume 47, Issue 3, Pages 939-952 (Mar 2014) "Gold-Catalyzed Cyclization Reactions of Allenol and Alkynol Derivatives", but they have a heap of other papers also.

  Another example, probably somewhat similar, of their use as a reactive synthon is BULLETIN OF THE KOREAN CHEMICAL SOCIETY Volume 28, Issue 1, Pages 17-28 (2007) "Indium and gallium-mediated addition reactions" - I have to admit I only read the abstract of this paper, but they appear to use azetidones as synthons in metal-mediated syntheses of a range of compounds.

Finally, the August edition of Chemical Reviews Vol 114, Issue 16 looks at small heterocycles in synthesis and has some interesing papers, inparticular:

• CHEMICAL REVIEWS Volume 114, Issue 16, Pages 7930-7953 "Chemical Synthesis of beta-Lactams: Asymmetric Catalysis and Other Recent Advances". This is a very good paper for you, I think.

• CHEMICAL REVIEWS Volume 114, Issue 16, Pages 8257-8322 "Four-Membered Ring-Containing Spirocycles: Synthetic Strategies and Opportunities". An interesting application of lactams in spiro molecule formation.

• CHEMICAL REVIEWS Volume 114, Issue 16, Pages 7954-8015 "Synthesis and Reactivity of 2-(Carboxymethyl)aziridine Derivatives". This looks at lactams being used as synthons for a range of molecules, here focussing on aziridines.

I hope some of these point you in the direction of what you are looking for.