851909-08-5

Basic information

• Product Name: (S)-N-Fmoc-2-(3'-butenyl)glycine
• Synonyms: (2S)-2-(Fmoc-amino)-5-hexenoic acid;Fmoc-(2S)-2-AMINO-5-HEXENOIC ACID;(S)-N-Fmoc-2-(3'-butenyl)glycine;(2S)-2-[[(9H-Fluoren-9-ylmethoxy)carbonyl]amino]-5-hexenoic acid;(S)-2-((((9H-Fluoren-9-yl)Methoxy)carbonyl)aMino)hex-5-enoic acid;(9H-Fluoren-9-yl)MethOxy]Carbonyl L-Homoallylglycine
• CAS NO: 851909-08-5
• Molecular Formula: C₂₁H₂₁NO₄
• Molecular Weight: 351
• EINECS: -0
• Mol File: 851909-08-5.mol

Chemical Properties

• Boiling Point: 573.744 °C at 760 mmHg
• Flash Point: 300.79 °C
• Appearance: /
• Density: 1.222
• Storage Temp.: 2-8°C
• PKA: 3.85±0.10(Predicted)
• CAS DataBase Reference: (S)-N-Fmoc-2-(3'-butenyl)glycine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-N-Fmoc-2-(3'-butenyl)glycine(851909-08-5)
• EPA Substance Registry System: (S)-N-Fmoc-2-(3'-butenyl)glycine(851909-08-5)

Safety Data

• Hazardous Substances Data: 851909-08-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-N-Fmoc-2-(3'-butenyl)glycine is used as a key building block for the synthesis of pharmaceuticals, particularly in the development of peptide-based drugs. Its unique chemical properties and reactivity enable the production of biologically active peptides with specific therapeutic effects.
Used in Biochemical Research:
In the field of biochemical research, (S)-N-Fmoc-2-(3'-butenyl)glycine serves as an essential component in the synthesis of novel peptides and proteins. Its presence allows researchers to explore the structure-function relationships of these biomolecules and gain insights into their biological activities.
Used in Peptide Synthesis:
(S)-N-Fmoc-2-(3'-butenyl)glycine is used as a crucial amino acid building block in peptide synthesis. The Fmoc protecting group ensures controlled reactivity and selectivity during the synthesis process, enabling the production of peptides with desired sequences and properties.
Used in Drug Discovery:
(S)-N-Fmoc-2-(3'-butenyl)glycine is employed as a valuable component in drug discovery efforts. Its incorporation into peptide and protein structures allows for the development of new therapeutic agents with potential applications in various diseases and conditions.
Used in Chemical Synthesis:
In the realm of chemical synthesis, (S)-N-Fmoc-2-(3'-butenyl)glycine is utilized as a versatile building block for the creation of complex organic molecules. Its unique functional group and reactivity contribute to the synthesis of novel compounds with potential applications in various industries, including pharmaceuticals, materials science, and agrochemicals.

Upstream product

• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 90989-12-1 (2S)-2-amino-5-hexenoic acid 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 
• 102774-86-7 9-fluorenylmethyl N-succinimidyl carbonate 

Downstream Products

• 851909-04-1 N-(N-(Fmoc)-L-homoallylglycyl)-N-(2,4-dimethoxybenzyl)-L-allylglycine methyl ester 
• 851908-96-8 methyl (E,3S,9S)-3-N-(Fmoc)amino-1-(2,4-dimethoxybenzyl)-2-oxo-2,3,4,5,8,9-hexahydro-1H-azonine-9-carboxylate 
• 1186613-29-5 C₈₀H₁₁₂N₇O₁₈P 
• 1312681-99-4 (3S,6R,7S,10S)-methyl 2-oxo-3-N-(Fmoc)amino-6-phenoxy-1-azabicyclo[5.3.0]decane-10-carboxylate 
• 1338002-17-7 N-9-fluorenylmethoxycarbonyl-L-decanylglycine 

Relevant articles and documents

Macrocyclic BACE1 inhibitors with hydrophobic cross-linked structures: Optimization of ring size and ring structure

Based on the X-ray crystallography of recombinant BACE1 and a hydroxyethylamine-type peptidic inhibitor, we introduced a cross-linked structure between the P1 and P3 side chains of the inhibitor to enhance its inhibitory activity. The P1 and P3 fragments bearing terminal alkenes were synthesized, and a ring-closing metathesis of these alkenes was used to construct the cross-linked structure. Evaluation of ring size using P1 and P3 fragments with various side chain lengths revealed that 13-membered rings were optimal, although their activity was reduced compared to that of the parent compound. Furthermore, the optimal ring structure was found to be a macrocycle with a dimethyl branched substituent at the P3 β-position, which was approximately 100-fold more active than the non-substituted macrocycle. In addition, the introduction of a 4-carboxymethylphenyl group at the P1′ position further improved the activity.

Rational Design and Synthesis of Modified Teixobactin Analogues: In Vitro Antibacterial Activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa

Teixobactin, a recently discovered depsipeptide that binds to bacterial lipid II and lipid III, provides a promising molecular scaffold for the design of new antimicrobials. Herein, we describe the synthesis and antimicrobial evaluation of systematically modified teixobactin analogues. The replacement of the Ile11 residue with aliphatic isosteres, the modification of the guanidino group at residue 10 and the introduction of a rigidifying residue, that is, dehydroamino acid, into the macrocyclic ring generated useful structure–activity information. Extensive antimicrobial susceptibility assessment against a panel of clinically relevant Staphylococcus aureus and Propionibacterium acnes strains led to the identification of the new lead compound, [Arg(Me)10,Nle11]teixobactin, with an excellent bactericidal activity (minimum inhibitory concentration (MIC)=2–4 μg mL?1). Significantly, the antimicrobial activity of several of the teixobactin analogues against the pathogenic Gram-negative Pseudomonas aeruginosa was “restored” when combined with the sub-MIC concentration of the outer membrane-disruptive antibiotic colistin. The antimicrobial effectiveness of a [Tfn10,Nle11]teixobactin (32 μg mL?1)–colistin (2 μg mL?1; 0.5×MIC) combination against P. aeruginosa PAO1 reveals, for the first time, an alternative therapeutic option in the treatment of Gram-negative infections.

Insight into Transannular Cyclization Reactions to Synthesize Azabicyclo[X.Y.Z]alkanone Amino Acid Derivatives from 8-, 9-, and 10-Membered Macrocyclic Dipeptide Lactams

An efficient method for synthesizing different functionalized azabicyclo[X.Y.0]alkanone amino acid derivatives has been developed employing electrophilic transannular cyclizations of 8-, 9-, and 10-membered unsaturated macrocycles to form 5,5-, 6,5-, 7,5-, and 6,6-fused bicylic amino acids, respectively. Macrocycles were obtained by a sequence featuring peptide coupling of vinyl-, allyl-, homoallyl-, and homohomoallylglycine building blocks followed by ring-closing metathesis. X-ray crystallographic analyses of the 8-, 9-, and 10-membered macrocyclic lactam starting materials as well as certain bicyclic amino acid products provided insight into their conformational preferences as well as the mechanism for the diastereoselective formation of specific azabicycloalkanone amino acids by way of transannular iodolactamization reactions. (Chemical Equation Presented).

Influence of α-methylation in constructing stapled peptides with olefin metathesis

Ring-closing metathesis is commonly utilized in peptide macro-cyclization. The influence of α-methylation of the amino acids bearing the olefin moieties has never been systematically studied. In this report, controlled reactions unambiguously indicate that α-methylation at the N-terminus of the metathesis sites is crucial for this reaction to occur. Also, we first elucidated that the E-isomers of stapled peptides are significantly more helical than the Z-isomers.

Prolonged stability by cyclization: Macrocyclic phosphino dipeptide isostere inhibitors of β-secretase (BACE1)

Cyclization of recently reported linear phosphino dipeptide isostere inhibitors of BACE1 via side chain olefin metathesis yielded macrocyclic BACE1 inhibitors. The most potent compound II-P1 (IC50 of 47 nM) and the corresponding linear analog I were tested for serum stability. The approach led to three times prolonged half life serum stability of 44 min for the macrocyclic inhibitor II-P1 compared to the linear compound I.

Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increased stability

The neuropeptide oxytocin 1 controls mammary and uterine smooth muscle contraction. Atosiban 2, an oxytocin antagonist, is used for prevention of preterm labor and premature birth. However, the metabolic lifetimes of such peptide drugs are short because of in vivo degradation. Facile production of oxytocin analogues with varying ring sizes wherein sulfur is replaced by carbon (methylene or methine) could be achieved by standard solid-phase peptide synthesis using olefin-bearing amino acids followed by on-resin ring-closing metathesis (RCM). These were tested for agonistic and antagonistic uteronic activity using myometrial strips taken from nonpregnant female rats. Peptide 8 showed agonistic activity in vitro (EC50 = 1.4 × 103 ± 4.4 102 nM) as compared to 1 (EC50 = 7.0 ± 2.1 nM). Atosiban analogues 17 (pA2 = 7.8 ± 0.1) and 18 (pA2 = 8.0 ± 0.1) showed substantial activity compared to the parent oxytocin antagonist 2 (pA2 = 9.9 ± 0.3). Carba analogue 35 (pA2 = 6.1 ± 0.1) had an agonistic activity over 2 orders of magnitude less than its parent 3 (8.8 ± 0.5). A comparison of biological stabilities of 1,6-carba analogues of both an agonist 8 and antagonist 18 versus parent peptides 1 and 2 was conducted. The half-lives of peptides 8 and 18 in rat placental tissue were shown (Table 2) to be greatly improved versus their parents oxytocin 1 and atosiban 2, respectively. These results suggest that peptides 8 and 18 and analogues thereof may be important leads into the development of a long-lasting, commercially available therapeutic for initiation of parturition and treatment of preterm labor.

Systematic study of the synthesis of macrocyclic dipeptide β-turn mimics possessing 8-, 9-, and 10- membered rings by ring-closing metathesis

A systematic study was performed to establish general synthesis protocols for forming enantiomerically pure macrocyclic dipeptide lactams. Focusing on macrocycles of 8-, 9-, and 10-membered rings, effective syntheses were achieved by a sequence featuring