Asymmetric Synthesis of β-Lactams Through the Staudinger Reaction and Their Use as Building Blocks of Natural and Nonnatural Products

Abstract

In the last two decades, the better understanding of the mechanistic aspects of the beta-lactams' biological activity and their inhibition, and the chemical exploitation of beta-lactams as synthetic intermediates in organic chemistry, have experienced a continuous and somewhat complementary advance. A prerequisite for such a development has been the accessibility of enantiopure beta-lactams. The latter are now routinely prepared most often through the ketene-imine cycloaddition reaction, also termed the Staudinger reaction. This review accounts for the recent progress made in the asymmetric synthesis of beta-lactams (with special emphasis in the Staudinger reaction approach), as well as in their use as synthetic intermediates en route to natural products, including alpha- and beta-amino acids and peptides derived therefrom.

Development of the β-lactam type molecular scaffold for selective estrogen receptor α modulator action: synthesis and cytotoxic effects in MCF-7 breast cancer cells

“…We are specifically interested in the development of novel heterocyclic ring scaffolds as ER antagonists 32 . Natural and synthetic azetidinone derivatives occupy a central place among medicinally important compounds due to their diverse and interesting biological activities 33 . Their importance is no longer exclusive due to the extensive clinical use of the b-lactam antibiotics but also because of their potential as intermediates in the synthesis of other types of compounds of biological interest.…”

Synthesis of novel spiro fused polycyclic β-lactam derivatives

“…We also conducted the reaction of the 2-unsubstituted dibenzo[b,f] [1,4]oxazepine (4a) with pentamethyleneketene affording spiro-β-lactam derivative 5a in satisfactory yield (56%) companied by amide 6a (Entry 6, Table 1). According to our previous results and suggested model, 28,29 imines with electron-deficient substituents favor the formation of β-lactam derivatives with an increased ring closure rate.…”

“…[1][2][3][4][5][6] For instance, the antibiotics penicillin, penam and penem have fused thiazolidine-β-lactam structures, and the antibiotics cephalosporin and cephem are fused dihydrothiazine-β-lactams. [1][2][3][4][5][6] The synthesis of bicyclic β-lactams has been a desirable goal since the discovery of penicillin and cephalosporin. Numerous heterocycle-fused β-lactam derivatives have been synthesized and assayed for biological activities.…”

“…Numerous heterocycle-fused β-lactam derivatives have been synthesized and assayed for biological activities. 1,4,5 Recently, spiro-β-lactams became particularly interesting compounds because their antiviral 7 and antibacterial properties 8 as well as their inhibition of cholesterol absorption 9 make them potentially useful candidates for drug development. They can also be used as β-turn mimetics in peptide chemistry [10][11][12] and, particularly 4-spiro-β-lactams, are synthetic precursors for cyclic α,α-disubstituted β-amino acids and peptide derivatives.…”

Simple, Highly Enantioselective Access to Quaternary 1,3,4,4‐Tetrasubstituted β‐Lactams from Amino Acids: A Solid‐Phase Approach

“…[9,10] Moreover, b-lactams are practical intermediates for the synthesis of a variety of high added value products (b-lactam synthon method). [11,12] In the peptidomimetics field, the blactam nucleus has also been used to stabilize peptide conformations, namely reverse b-turns. [13] The interest of b-lactams in these three fields, biomedicine, organic synthesis and peptidomimetics, has encouraged extensive efforts toward the preparation of new 2-azetidinone derivatives.…”