150458-43-8

Upstream product

• 94744-50-0 N-[(9H-fluoren-9-ylmethoxy)carbonyl]-α-aminoisobutyric acid 

Downstream Products

• 211372-14-4 Fmoc-Aib-Aib-OBzl 

Relevant academic research and scientific papers

Fmoc Amino Acid Fluorides: Convenient Reagents for the Solid-Phase Assembly of Peptides Incorporating Sterically Hindered Residues

Fmoc amino acid fluorides, recently shown to be a new class of rapid-acting acylating agents in peptide synthesis are well suited for the solid-phase synthesis of medium-sized peptides such as ACP(65-74), magainin-II-amide, and h-CRF.The most important advantage of these reagents is their high reactivity in the coupling of sterically hindered amino acid residues, such as α-aminoisobutyric acid (Aib), results which are at least partly due to the small size of the fluoride leaving group.Both h-(Aib32-35)-CRF(1-41), bearing four consecutive Aib-residues, and alamethicin acid, neither previously accessible by solid-phase synthesis, were successfully synthesized via acid fluorides using unusually short coupling times.In contrast, attempted syntheses via UNCA's and PyBroP activation, both reported to be well suited for sterically hindered systems, failed to give the desired peptides.These remarkable differences prompted a more detailed comparison of the acid fluorides with symmetric anhydrides, UNCA's, and the PyBroP activation technique.Side products formed during the acylation of hindered amino components by Fmoc-Aib-NCA were identified and their formation rationalized.These side products could have their origin in the demonstrated instability of Fmoc-NCA's in the presence of tertiary bases or in a diversion of the position of attack on the NCA from the more hindered to the less-hindered carbonyl function by a bulky nucleophile.Clearly caution is required when such bases are employed to enhance coupling rates for hindered systems.

Pyrrolo[3,2-e][1,4]diazepin-2-one synthesis: A head-to-head comparison of soluble versus insoluble supports

Aryldiazepin-2-ones are known as "privileged structures", because they bind to multiple receptor types with high affinity. Toward the development of a novel class of aryldiazepin-2-one scaffolds, the synthesis of pyrrolo[3,2-e][1,4]diazepin-2-ones on a support was explored starting from N-(PhF)-4-hydroxyproline and featuring an acid-catalyzed Pictet-Spengler reaction to form the diazepine ring. Three supports [Wang resin, tetraarylphosphonium (TAP) soluble support, and Merrifield resin] were examined in the synthesis of the heterocycle and exhibited different advantages and disadvantages. Wang resin proved effective for exploratory optimization of the synthesis by identification of intermediates after resin cleavage under mild conditions; however, the acidic conditions of the Pictet-Spengler reaction caused premature loss of resin-bound material. Direct monitoring of reactions by TLC, RP-HPLC-MS, and in certain cases NMR spectroscopy was possible with the TAP support, which facilitated purification of intermediates by precipitation; however, incomplete precipitation of material led to overall yields lower than those from solid-phase approaches on resin. Merrifield resin proved stable to the conditions for the synthesis of the pyrrolo[3,2-e][1,4]diazepin-2-one targets and would be amenable to "split-and-mix" chemistry; however, relatively harsh conditions were necessary for final product cleavage. Perspective for the application of different solid-phase approaches in heterocycle library synthesis was thus obtained by demonstration of the respective utility of the three supports for preparation of pyrrolo[3,2-e][1,4] diazepin-2-one.

Complex polyfluoride additives in Fmoc-amino acid fluoride coupling processes. Enhanced reactivity and avoidance of stereomutation.

[reaction: see text] Isolated Fmoc amino acid fluorides have previously been shown to be among the most efficient reagents for peptide bond formation. Now, it has been found that anionic, polyhydrogen fluoride additives are capable of diverting many of the classical peptide coupling processes to acid fluoride couplings. Examples include the use of N-HBTU or N-HATU and the carbodiimide technique. As HF-containing species, these additives provide a more suitable medium for the coupling of systems that are sensitive to loss of configuration at the reactive carboxyl function.

Convergent synthesis of (-)-mirabazole C using a chloroimidazolidium coupling reagent, CIP

Convergent synthesis of (-)-mirabazole C (1), a tetra thiazoline/thiazole alkaloid isolated from blue-green alga, has been described. The successive thiazoline rings of (-)-mirabazole C were formed by a single-step cyclization mediated by TiCl4 treatment of tripeptide amide 4. Convergent synthesis of the key intermediate 33 derived from three 2-methylcysteine residues was first achieved using a newly developed coupling reagent, 2-chloro-1,3-dimethylimidazolidium hexafluorophosphate (CIP). The effectiveness of CIP for the coupling of α,α-dialkyl amino acids and the reaction pathway of the activation were clarified by the syntheses of model peptides containing an α,α-dimethylamino acid. A practical method of asymmetric synthesis of 2-methylcysteine by alkylation of 2,4-cis-oxazolidinone 23 has also been described.

Efficient coupling of α,α-dimethyl amino acid using a new chloro imidazolidium reagent, CIP

CIP (2-chloro-1,3-dimethylimidazolidium hexafluorophosphate) was an efficient coupling agent for N(α)-protected α-aminoisobutyric acid (Aib) in the presence of an additive. The reactivity was enhanced markedly by a catalytic amount of additive in the order of HOAt ~ HODhbt > DMAP > HOBt. These couplings occurred without detectable racemization.