β-Lactams as Versatile Intermediates in α- and β-Amino Acid Synthesis

Abstract

ACCOUNT 1813 b-Lactams as Versatile Intermediates in aand b-Amino Acid Synthesis b-Lactams a s V e r s a t i l e I n t e r m e d i a t e s i n a-a n d b-Amino A c i d S y n t h e s i s Abstract: The use of b-lactams as synthetic intermediates has recently found considerable interest, driven by the accessibility of enantiomerically pure b-lactam building-blocks and by the discovery of selective methods for the b-lactam ring opening. N 1 -C 2 and C 2 -C 3 bond cleavage of b-lactams can now be effected cleanly by different nucleophiles, in an intra-or intermolecular fashion, under isomerization-free conditions. By this way, an array of diverse, densely functionalized, cyclic as well as open chain, aand b-amino acid derivatives, including peptides, have been synthesized. Examples from our laboratory and from others are provided.

Crystal structure of N-[1',1'-(diphenyl)-hydroxymethyl]-3(S)-[1'(R)- hydroxyethyl]-4(S)-(t-butyl-oxomethyl)-azetidin-2-one, C23H27NO4, an unexpectedly stable intermediate in the photochemical cleavage of N-benzhydryl protecting group

“…Chiral functionalized azetidinones (b-lactams) are valuable key-intermediates in organic synthesis for the preparation of various biologically active compounds [1], particularly in the field of antibiotics related to the large family of penicillins [2]. Recently, we became interested in the synthesis of novel precursors of carbapenems [3,4].…”

Advanced procedure for the enzymatic ring opening of unsaturated alicyclic β-lactams

“…7 Such compounds can be used as precursors of b-lactams; 8;9 as building blocks for the synthesis of modified peptides with increased activity and stability 10;11 or in drug research. [12][13][14] Cyclic b-lactams are also important as intermediates in the synthesis of b-amino acids, 15 short peptide segments, 16 taxoid antitumour agents, 17 alkaloids 18 and heterocycles of biological and medicinal importance. 19 A number of enzymatic syntheses of b-amino acids or their derivatives and b-lactams in enantiomerically pure form have been elaborated over the past few years.…”

Chemoenzymatic preparation of fluorine-substituted β-lactam enantiomers exploiting Burkholderia cepacia lipase

“…Step 4. donor which, as was shown previously for the reaction of N-Boc activated b-lactams with alcohols, 5,6,8 likely gives fluorotaxol analogues when coupled with the free alcohol group of the taxane ring.…”

“…[1][2][3][4][5][6][7] The substitution of one or more of the hydrogen atoms with isosteric fluorine in the b-lactam skeleton can further enhance their importance for medicinal chemistry, often leading to derivatives with desirable effects on physiological activity and metabolism. The (S)-enantiomer of 3,3-difluoro-4-phenyl-2-azetidinone (S)-1a (Scheme 1) is a good example of an activated acyl 0957-4166/$ -see front matter Ó 2007 Elsevier Ltd. All Step 1.…”