The Synthesis of Diastereo- and Enantiomerically Pure β-Aminocyclopropanecarboxylic Acids

Abstract

The synthesis of diastereo- and enantiomerically pure beta-aminocyclopropanecarboxylic acids (beta-ACCs) is described. Starting from pyrrole, (rac)-4 is readily obtained, which was kinetically resolved by enzymatic hydrolysis. Subsequent oxidation of (-)-4 and deformylation gives rise to the cis-beta-ACC derivative (ent)-9, while (+)-10 was converted to the trans-beta-ACC derivative 8. Both 8 and (ent)-9 and their benzyl esters 13 and 16, being conformationally restricted beta-alanine or gamma-aminobutyric acid (GABA) derivatives, represent useful building blocks for peptides containing unnatural amino acids.

A New Strategy for the Stereoselective Synthesis of 1,2,3-Trisubstituted Cyclopropanes

“…[8] Ozonolysis of 5 smoothly yielded the β-amino aldehyde 2 (88% yield), which proved to undergo highly selective addition reactions with nucleophiles. [9] Only a few cases have been reported of nucleophilic additions to cyclopropanecarbaldehydes and cyclopropyl ketones proceeding with high diastereocontrol.…”

Investigation into Factors Influencing Stereoselectivity in the Reactions of Heterocycles with Donor−Acceptor-Substituted Rhodium Carbenoids

“…This reactivity is different from the reactions of ethyl diazoacetate with N-Boc-pyrrole or furan, where the monocyclopropane is typically formed. 13,14,16,17 This behavior presumably demonstrates the greater selectivity of the donor-acceptor carbenoids because they are able to selectively react with the monocyclopropane even in the presence of an excess of aromatic starting material. The reaction with N-Boc-pyrrole 3 is a clear example of this trend because no monocyclopropane product 6 is observed even when 6 equiv of the N-Boc-pyrrole 3 is used (Scheme 2), and even when 3 is used as solvent, a significant amount (34%) of 5 is isolated (Scheme 3).…”

Targeting αvβ3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides

“…In the search for non peptidic RGD-containing cyclic systems based on II'/ arrangement with the -turn centred on Gly, classic dipeptide mimetics based on amino pyrrolidinone motifs were used by Kessler to graft macrocycles (54) and (55) (Fig. (8)) [36].…”

“…The synthetic strategy for the preparation of both enantiomers of -Acc relied on the cyclopropanation of N-Bocpyrrole (96) with methyl diazoacetate, under phenylhydrazine-activated catalytic copper(II) triflate promotion (Scheme 4) [55]. Both enantiomers of (97) were isolated after kinetic resolution by enzymatic hydrolysis with lipase L2.…”