Stereoselective Synthesis of l-2-(Carboxycyclopropyl)glycines via Stereocontrolled 1,3-Dipolar Cycloadditions of Diazomethane on Z- and E-3,4-l-Didehydroglutamates OBO Esters
“…For example, β-cyclopropylalanine ( 12 , 15, and 16 , Scheme , n = 1, R 1 = R 2 = H) is a potent antagonist to E. coli ATCC 9723 and inhibits spore germination of Pyricularia oryzae Cav., the causative agent of rice blast disease . The cyclopropane ring can be introduced into amino acids by a number of methods, which include (1) metal-promoted cyclopropanation or carbene addition reactions, (2) glycine enolate alkylation with cyclopropylmethyl halides, and (3) Michael-induced ring closure by glycine enolates …”
[reaction: see text] Photolysis at 254 nm of neat (no solvent) unsymmetrical diacyl peroxides derived from cyclopropane carboxylic acids and l-aspartic acid generates protected beta-cyclopropylalanines in reasonable yields. Orthogonally protected 3-(trans-2-aminocyclopropyl)alanine (21), a key constituent of the antitumor agent belactosin A, as well as protected hypoglycin A (26), a causative agent of Jamaican vomiting sickness, is synthesized by this approach with coupling of the intermediate substituted cyclopropyl radicals proceeding predominantly with retention of configuration (dr >or= 95:5).
“…For example, β-cyclopropylalanine ( 12 , 15, and 16 , Scheme , n = 1, R 1 = R 2 = H) is a potent antagonist to E. coli ATCC 9723 and inhibits spore germination of Pyricularia oryzae Cav., the causative agent of rice blast disease . The cyclopropane ring can be introduced into amino acids by a number of methods, which include (1) metal-promoted cyclopropanation or carbene addition reactions, (2) glycine enolate alkylation with cyclopropylmethyl halides, and (3) Michael-induced ring closure by glycine enolates …”
[reaction: see text] Photolysis at 254 nm of neat (no solvent) unsymmetrical diacyl peroxides derived from cyclopropane carboxylic acids and l-aspartic acid generates protected beta-cyclopropylalanines in reasonable yields. Orthogonally protected 3-(trans-2-aminocyclopropyl)alanine (21), a key constituent of the antitumor agent belactosin A, as well as protected hypoglycin A (26), a causative agent of Jamaican vomiting sickness, is synthesized by this approach with coupling of the intermediate substituted cyclopropyl radicals proceeding predominantly with retention of configuration (dr >or= 95:5).
“…Recently, Lajoie and co-workers have developed a new strategy for the synthesis of a variety of amino acids based on the elaboration of a chiral serine aldehyde equivalent in which the carboxylic acid is protected as a 2,6,7-trioxabicyclo[2.2.2]octane (OBO ester). 5,6 In this work, we chose a 2,7,8-trioxabicyclo[3.2.1]octane (ABO ester) as a carboxyl protecting group. The ABO ester is more Brønsted acid-stable and easy to prepare.…”
mentioning
confidence: 99%
“…4 Cyclopropanation of the olefin 4 was carried out by 1,3-dipolar cycloaddition of diazomethane followed by photolysis of the resultant pyrazoline 7 in the presence of benzophenone as a photosensitizer. 6 When Pd(OAc) 2 -catalyzed cyclopropanation of the olefin 4 with diazomethane was tried, no cycloadduct was produced. Generally, this type of cyclopropanation gives a mixture of diastereomers; however, the bicyclic compound 8 was obtained as a single diastereomer in 61% yield, which could be converted to enantiomerically pure ( > 99% ee) (2S,3S,4R)-(carboxycyclopropyl)glycine (9, CCG-III) 9 in a single step by acid hydrolysis in 61% yield.…”
Some reactions such as catalytic hydrogenation, Diels-Alder reaction, cyclopropanation, dihydroxylation, and Michael addition of a novel 3,4-didehydropyroglutamate derivative, in which the carboxylic group is protected as an ABO ester, are examined and found to take place in a stereospecific manner giving 3- and/or 4-substituted pyroglutamate derivatives without loss of enantiomeric purity at the alpha-position.
“…(2 S ,1‘ S ,2‘ S )-2-(Carboxycyclopropyl)glycine ( l -CCG-I), which restricts the conformation of l -glutamic acid in the extended form, is a potent and selective agonist of m-GluRs. The neurobiological activity of these compounds has led to several synthetic studies of this class of molecules. , 1 …”
Introduction of natural menthol as the chiral auxiliary in a gamma-Br-alpha,beta-unsaturated ester leads to enantioselective generation of three chiral centers in a single step on reaction with a glycine anion equivalent to provide L-CCG-I in 94% ee.
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