Methanoamino acids

Applying only a few simple operations, the dibenzylaminocyclopropanes 133-R, prepared as described above from N,N-dibenzyl-a-benzyloxyacetamide in 33—48% yield (see Scheme 11.16 and Table 11.9), have been transformed into N-Boc-protected methyl esters of amino acids 138-R containing a cyclopropane moiety (Scheme 11.35) [109,110], Several such analogues of natural amino acids, also referred to as methanoamino acids, exhibit important biological activities [128],... 

Amino-4-cyclopropylidenebutanoic acid (2S)-56, is a methylenecyclopro-pane substituted alanine which can be considered as a non-natural isomer of hypoglycine A 51. It has recently been synthesized racemic [61] and enantiome-rically pure [62]. Biological assays have shown that at relatively high concentration the 5,6-methanoamino acid 56 inhibits the metabolism of pyruvate into glucose, but 56 is not active in inducing the mitochondrial oxidation of fatty acids,Eq. (21) [63]. 

Due to their physiological importance, considerable efforts are currently devoted towards the total synthesis of 2,3-methanoamino acids (ACCs). The parent compound ACC 71 has been readily prepared from acrolein, through the base-induced (K2CO3) cyclization of 2-amino-4-chlorobutyronitrile [96] or from one-pot Strecker reaction of cyclopropanone hemiacetal [97]. 

L-2-(l-Methylcyclopropyl)glycine 105 was isolated from the culture broth of M. miyakanonensis, and this 3,4-methanoamino acid exhibits an antimicrobial activity against E. coli on a synthetic medium, Eq. (41) [137]. 

Preparative Methods substituted 2,3-methanoamino acids are difficult to prepare. Unfortunately, most of the reported syntheses give racemic materials whereas stereochemically pure compounds are required for studies of cyclopropane-based peptidomimetics. The only 2,3-methanologs of protein amino acids prepared in optically active form are ( )- and (Z)-cyclo-Phe and -Tyr, all four stereoisomers of cyc/o-Met, (Z)-cyclo-Arg and (25,35)-(Z)-cyc/o-Trp, although several routes to enantio-enriched 2,3-methanologs of simple nonproteogenic amino acids have been reported. " The most practical synthesis of the title compound is that based on a diastereoselective, rhodium-catalyzed cyclopropanation reaction. ... 

At the present time, 2,3-methanoamino acid analogs can only be viewed as reagents in the context of syntheses of peptidomimetics. Consequently, this entry describes only that chemistry related to incorporation of protein amino acid methanologs into peptide sequences. 

Charette, A B, Cote, B, Stereoselective s3mthesis of all four isomers of coronamic acid a general approach to 3-methanoamino acids, J. Am. Chem. Soc., 117, 12721-12732, 1995. 

Natural occurrence, syntheses, and the use of 1-aminocyclopropanecar-boxylic acid (ACA) and other 2,3-methanoamino acids for preparation of cyclic peptides and heterocyclic derivatives of ACA 07CRV4493. 

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