Ring-opening reactions of certain 2-carbonyl-substituted cyclopropylamines

Ring-opening, cycloaddition and rearrangement reactions of nitrogen-substituted cyclopropane derivatives

“…163,164 However, the related amides or carbamates are usually fairly stable. 165 It is worth noting that 85 is formally a rearranged form of the zwitterion resulting from ringcleavage of 84. An earlier particularly elegant related example is shown in Scheme 101,…”

Incorporation of Conformationally Constrained ?-Amino Acids into Peptides

“…It appeared attractive to investigate the synthesis of cyclopropane containing peptide derivatives using this methodology since there is significant interest in the synthesis of cyclopropane derivatives of amino acids and peptides [8,64,65]. Most work to date has concentrated on h-aminocyclopropane carboxylic acid and its derivatives [66], rather than i-aminocyclopropane carboxylic acid which, like all cyclopropanes bearing electron withdrawing and electron donating substituents on adjacent ring positions, is prone to ring-opening [67][68][69][70] as shown in Scheme 8. Peptides derived from i-aminocyclopropane carboxylic acid should be stable however, due to delocalization of the nitrogen lone pair of electrons [71,72].…”

Synthetic analogs for the study of GABA as a neurotransmitter

“…Only muscimol and dihydromuscimol are more potent at inhibiting GABA binding. With respect to uptake, the (+)-cis-IS,dR (48) and (-)-trans-lR,dR stereoisomers were potent inhibitors being approximately twice as potent as GABA 106 …”

“…While 5-(2-aminoethyl)hydantoin ( 9 3 ) is inactive with respect to GABA binding, uptake and tran~amination,~' quisquaIamine (94) de-92 93 94 112 ALLAN pressed electrical activity in frog, rat, and mouse spinal cord preparations presumably by a predominately GABA mimetic action although bicuculline antagonism could not be demonstratedin uiuo or was accompanied by strychnine antagonism in The acidic heterocyclic functionality of kojic amine (95),144 like muscimol (82), allows the molecule to penetrate the blood-brain barriers in contrast to GABA. As in the case of noncyclized derivatives of muscimol, the activity of kojic amine derivatives decreased on (i) alkyl substitution with an N-methyl, an a-methyl or a 6-methyl substitutent, (ii) introduction of a nitrogen into the heterocyclic ring as in 96a,b, or (iii) on changing the spatial separation of the amino group and the acidic functionality as in 97 and 98.144 103 106 natural products such as tutin and coriamyrtin share the convulsant action of picrotoxin but are also nonionic in solution and therefore difficult to investigate microelectrophoretically.4 Dihydropicrotoxinin is only slightly less active as a convulsant than picrotoxinin. It can be made in radiolabeled form and has been used to investigate convulsant binding SiteS.147,148 Unlike bicuculline, picrotoxin appears to act at GABA regulated membrane chloride channels rather than at the GABA receptors of the GABA receptor-ionophore complex149 consistent with the noncompetitive nature of its antagonism.…”