159303-54-5Relevant articles and documents
Synthesis of Conformationally Constrained Dipeptide Mimetics with Azabicyclo[4,3,0]nonanone and Azabicyclo[5,3,0]decanone Scaffolds
Xi, Wanlin,Du, Lei,Zhang, Liping,Sun, Haiying
, p. 10182 - 10188 (2020)
A general and efficient method for the synthesis of azabicyclo[4,3,0]nonanone and azabicyclo[5,3,0]decanone amino acid derivatives was developed with the palladium-catalyzed coupling of intermediates 9 and 10 with BocNH2 and Boc2NH and the following reduction of the C-C double bond by hydrogenation as the key steps. The exploration of the synthesis of C6-substituted dipeptide mimetics from 9 and 10 using Suzuki coupling as the key reaction has also been performed.
Dipeptide stimulant based on azabicyclo[X, Y, 0]alkanone skeleton, and preparation method thereof
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, (2020/08/30)
The invention discloses a dipeptide stimulant based on an azabicyclo[X, Y, 0]alkanone skeleton, and a preparation method thereof. The dipeptide stimulant has a structure shown in the description; andin the structure, n = 1-4, R is an amino group, an alkylamino group, a substituted alkylamino group, a nitrogen atom-substituted or non-substituted alkylamido group, a nitrogen atom-substituted ornon-substituted aryl amido group, a nitrogen atom-substituted or non-substituted heteroaryl amido group, a nitrogen atom-substituted or non-substituted alkoxy amido group, a hydroxyl group, a substituted alkoxy group, a substituted alkyl group, a substituted aryl group or a substituted heterocyclic aryl group, X is O or NR, R and R are a hydrogen atom, a substituted or unsubstituted alkylgroup, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group, and the substituent refers to an alkyl group, anaphthenic base, an aryl group or a heterocyclic aryl group. The invention also provides a preparation method of the dipeptide stimulant. The dipeptide stimulant has the advantages of good metabolic stability, high bioavailability and strong membrane permeability, and the preparation method has the advantages of short route, high efficiency and versatility.
Paired Utility of Aza-Amino Acyl Proline and Indolizidinone Amino Acid Residues for Peptide Mimicry: Conception of Prostaglandin F2α Receptor Allosteric Modulators That Delay Preterm Birth
Mir, Fatemeh M.,Atmuri, N. D. Prasad,Bourguet, Carine B.,Fores, Jennifer Rodon,Hou, Xin,Chemtob, Sylvain,Lubell, William D.
, p. 4500 - 4525 (2019/05/17)
Peptide mimicry employing a combination of aza-amino acyl proline and indolizidinone residues has been used to develop allosteric modulators of the prostaglandin F2α receptor. The systematic study of the N-terminal phenylacetyl moiety and the conformation and side chain functions of the central turn dipeptide residue has demonstrated the sensitive relationships between modulator activity and topology. Examination of aza-Gly-Pro and aza-Phe-Pro analogs 2a and 2b in a murine preterm labor model featuring treatment with lipopolysaccharide demonstrated their capacity to extend significantly (>20 h) the average time of delivery offering new prototypes for delaying premature birth.
An efficient approach to asymmetric synthesis of dipeptide β-turn mimetics: Indolizidinone amino acids
Wang, Wei,Xiong, Chiyi,Hruby, Victor J
, p. 3159 - 3161 (2007/10/03)
Azabicyclo[X.Y.0] alkane amino acids are rigid dipeptide β-turn mimetics with great potential applications for drug discovery. The lack of efficient methods to synthesize these compounds is a major bottleneck in this field. Herein we report an efficient a
Anodic amide oxidation/olefin metathesis strategies: Developing a unified approach to the synthesis of bicyclic lactam peptidomimetics
Beal, Laura M,Liu, Bin,Chu, Wenhua,Moeller, Kevin D
, p. 10113 - 10125 (2007/10/03)
In connection with efforts to build constrained peptidomimetics for the endocrine hormone TRH, a general strategy for the construction of bicyclic lactam peptide building blocks has been developed. This strategy used an anodic amide oxidation to selective
Rigid dipeptide mimetics: Efficient synthesis of enantiopure indolizidinone amino acids
Lombart, Henry-Georges,Lubell, William D.
, p. 9437 - 9446 (2007/10/03)
An effective means to synthesize indolizidinone amino acids has been developed and furnishes all possible stereoisomers of these conformationally rigid mimetics of peptide secondary structures. Inexpensive glutamic acid was employed as chiral educt in a Claisen condensation/reductive amination/lactam cyclization sequence that furnished stereoselectively azabicyclo[3.4.0]alkane amino acid 1. Enantiopure (3S,6S,9S)- and (3R,6R,9R)-2-oxo-3-N-(BOC)amino-1-azabicyclo[4.3.0]nonane-9-carboxylic acids ((3S,6S,9S)- and (3R,6R,9R)-1) were respectively synthesized from L- and D-N-(PhF)glutamates 2 (PhF = 9-(9-phenylfluorenyl)). Slow addition of sodium bis(trimethylsilyl)amide to 2 provided good to excellent yields of β-keto esters 3, which were subsequently hydrolyzed and decarboxylated to give symmetric α,ω-bis[N-(PhF)amino]azelate δ-ketones 5. Augmentation of hydrogen pressure increased diastereoselectivity in reductive aminations with 5 and afforded 5-alkylprolines 8 and 10. Lactam formation on exposure of 10 to triethylamine and N-protection with di-tert-butyl dicarbonate gave methyl-2-oxo-3-[N-(BOC)amino]-1-azabicyclo[4.3.0]nonane-9-carboxylate (12) which on C-terminal ester hydrolysis with hydroxide ion gave enantiopure [N-(BOC)amino]indolizidinone acid 1. Alternatively, hydride addition to ketone 5a gave symmetric α,ω-bis[N-(PhF)amino]azelate δ-alcohol 7a, which upon mesylation and intramolecular S(N)2 displacement by the PhF amine gave specifically cis-5-alkylproline 15 that was similarly converted to (3S,6S,9S)-1. In addition, epimerization of the C-9 stereocenter of (3S,6S,9S)-[N-(BOC)amino]indolizidinone methyl ester 12 with NaN(SiMe3)2 and ester hydrolysis gave (3S,6S,9R)-indolizidinone amino acid (3S,6S,9R)-1. By providing efficient methodology for synthesizing all of the possible stereoisomers of enantiopure indolizidinone amino acid 1, our route is specifically designed to enhance the general use of these peptide mimetics in the exploration of conformation-activity relationships of various biologically active peptides.
Synthesis of enantiopure α,ω-diamino dicarboxylates and azabicycloalkane amino acids by Claisen condensation of α-[N-(phenylfluorenyl)amino] dicarboxylates
Lombart,Lubell
, p. 6147 - 6149 (2007/10/02)
Enantiomerically pure (3S,6S,9S)-2-oxo-3-(N-BOC-amino)-1-azabicyclo[4.3.0]nonane-9-carboxyli c acid ((3S,6S,9S)-1) was prepared in 39% overall yield from α-tert-butyl γ-methyl N-(9-(9-phenylfluorenyl))glutamate (5) using a Claisen condensation/reductive amination/lactam cyclization sequence.
