89813-47-8

Usage

Chemical Properties

Yellowish oil

Upstream product

• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 100-44-7 benzyl chloride 
• 24424-99-5 di-tert-butyl dicarbonate 
• 51-35-4 4R-4-hydroxyproline 
• 100-51-6 benzyl alcohol 
• 871979-68-9 3-[2-((4R)-acetoxy-1-tert-butoxycarbonyl-(2S)-pyrrolidinyl)-5-thiazolyl]propionic acid methyl ester 
• 1738-76-7 glycine benzyl ester p-toluenesulfonic acid salt 
• 1332341-02-2 benzyl (2S)-2-Boc-amino-3-(2-oxiranyl)propionate 
• 100-39-0 benzyl bromide 
• 88501-00-2 (2S,4R)-4-hydroxyproline benzyl ester p-toluenesulfonate 

Downstream Products

• 134286-67-2 N-(tert-Butoxycarbonyl)-O-(3,4,6-tri-O-acetyl-2-desoxy-2-iod-α-D-mannopyranosyl)-L-hydroxyprolin-benzylester 
• 154456-97-0 2-benzyl 1-(tert-butyl) (S)-4-oxopyrrolidine-1,2-dicarboxylate 
• 185304-16-9 (2S,4S)-4-(Toluene-4-sulfonyloxy)-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester 
• 288582-37-6 N-[(2S,4S)-4-[2-(benzyloxycarbonyl)-1-(tert-butyloxycarbonyl)pyrrolidinyl]]-D-serine benzyl ester 
• 288582-33-2 N-[(2S,4S)-4-[2-(benzyloxycarbonyl)-1-(tert-butyloxycarbonyl)pyrrolidinyl]]-L-serine benzyl ester 
• 587888-04-8 N-tert-butoxycarbonyl-(2S,4S)-4-fluoroproline benzyl ester 
• 874162-95-5 (2S,4S)-1-(tert-butoxycarbonyl)-4-bromoproline benzyl ester 
• 865295-35-8 2-benzyl 1-(tert-butyl) (2S,4R)-4-((methylsulfonyl)oxy)pyrrolidine-1,2-dicarboxylate 
• 862079-84-3 benzyl (2S,4S)-1-tert-butoxycarbonyl-4-cyano-2-pyrrolidinecarboxylate 
• 132622-69-6 (2S,4R)-4-amino-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid 
• 132622-66-3 cis-1-(1,1-dimethylethyoxycarbonyl)-4-amino-L-proline 
• 185304-19-2 (2S,4R)-2-benzyl 1-tert-butyl 4-azidopyrrolidine-1,2-dicarboxylate 
• 470482-41-8 (2S,4S)-1-[(tert-butoxy)carbonyl]-4-(trifluoromethyl)pyrrolidine-2-carboxylic acid 
• 474417-79-3 (2S,4S)-N-tert-butoxycarbonyl-4-difluoromethylproline 

Relevant academic research and scientific papers

PI3K INHIBITORS AND USES THEREOF

The development of a new, targeted drug delivery paradigm coupled to improved PI3K inhibitors (e.g., PI3Kα inhibitors) represents a significant advance in cancer therapy. Provided herein are compounds, such as compounds of Formula (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds provided herein are PI3K (e.g., PI3Kα) inhibitors and are therefore useful for the treatment and/or prevention of various diseases (e.g., proliferative diseases such as cancer). Also provided herein are nanoparticles and nanogels (e.g., P-selectin targeting nanoparticles) comprising PI3K inhibitors, such a compound described herein. In certain embodiments, a nanoparticle or nanogel described herein encapsulates a compound described herein for targeting delivery to cancer cells or tumors.

Design and synthesis of plant cyclopeptide Astin C analogues and investigation of their immunosuppressive activity

To further investigate on the structure-activity relationships of immunosuppressive Astin C, seventeen analogues 1–17 were designed and synthetized via amino acid substitution strategy by the solid-phase peptide synthesis method for the first time. In comparison with Astin C (IC50 = 12.6 ± 3.3 μM), only compounds 2 (IC50 = 38.4 ± 16.2 μM), 4 (IC50 = 51.8 ± 12.7 μM), 5 (IC50 = 65.2 ± 15.6 μM), and 8 (IC50 = 61.8 ± 12.4 μM) exhibited immunosuppressive activity in the Lymph node cells of mice. These results showed that the Astin C analogues containing D-amino acid residues, hydrophobic long-chain alkyl substituents, and aryl substituents performed better than those carrying hydrophilic amino acid residues and short-chain alkyl substituents. Moreover compounds 15, 16, and 17 had no immunosuppressive activity, which suggested that cis-3,4-dichlorinated proline played an important role in the immunosuppressive activity of Astin C.

A short diastereoselective synthesis of cis-(2S,4S) and cis-(2R,4R)-4-hydroxyprolines

A concise synthesis of (2R,4R)-4-hydroxyproline (1) and (2S,4S)-4-hydroxyproline (2) has been developed in enantiomerically pure form from commercially available starting materials with excellent diastereoselectivity. The tightly bound chelation controlled transition state formed during the 5-exo-tet ring closure reaction is assumed to be the origin of high diastereoselectivity.

Epoxy amino acids produced from allylglycines intramolecularly cyclised to yield four stereoisomers of 4-hydroxyproline derivatives

Derivatives of 2-amino-4-pentenoic acid (allylglycine) were efficiently resolved using Subtilisin or acylase. The side-chain unsaturated bond of the enantiomerically pure amino acid with tert-butoxycarbonyl (Boc) protection was smoothly epoxidized with m-chloroperbenzoic acid. When the Boc protection of the amino group was removed, the amino group intramolecularly attacked the side-chain epoxide, generating compounds with five-membered rings: the 4-hydroxyproline derivatives. Two diastereomeric products were formed through the cyclisation reaction, for example, (2S,4S)-4-hydroxyproline benzyl ester (cis-8) and (2S,4R)-4-hydroxyproline benzyl ester (trans-8) were formed from (2S)-amino acid with a side-chain epoxide. Compound (2S,4S)-4-hydroxyproline benzyl ester (cis-8) was transformed to a lactone (cis-hydroxyproline lactone, 10) with the removal of benzyl alcohol. The cis-conformation was essential for the intramolecular ester exchange reaction; in fact, no lactone formation was observed for the trans isomer (trans-8). The separation of cis-hydroxyproline lactone and the trans-isomeric hydroxyproline benzyl ester was facile and clear, in contrast to the difficult separation of cis- and trans-hydroxyproline derivatives. Thus, two diastereomers of hydroxyproline derivatives for l-hydroxyproline and also for d-hydroxyproline were obtained, i.e., four diastereomers of hydroxyproline derivatives.

SUBSTITUTED BICYCLIC 1-CARBOXYLIC-ACID (BENZYL-CYANO-METHYL)-AMIDES INHIBITORS OF CATHEPSIN C

This invention relates to bicyclic 1-carboxylic-acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and their use in methods of treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

SUBSTITUTED BICYCLIC 1-CARBOXYLIC-ACID (BENZYL-CYANO-METHYL)-AMIDES INHIBITORS OF CATHEPSIN C

This invention relates to bicyclic 1-carboxylic-acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.

Direct asymmetric aldol reactions in water catalysed by a highly active C2-symmetrical bisprolinamide organocatalyst

A novel C2-symmetrical bisprolinamide organocatalyst was synthesised and used to facilitate asymmetric direct aldol reactions in a water emulsion. Reactions were performed at room temperature with very low catalyst loadings (1-2.5 mol%) without the required use of additives, co-catalysts or extended reaction times (24 h). This catalyst system was then used with a variety of aldehyde substrates showing good reaction generality for benzaldehydes with cyclohexanone (dr range 77/23 to 99/1, anti/syn; ee range 33% to 99%) and moderate scope with cyclopentanone (dr range 45/55 to 76/24, anti/syn; ee range 14% to 68%). Ultra-low catalysts loadings (0.1 and 0.05 mol%) were also investigated demonstrating catalyst turnover numbers in the order of 1000.

Novel sulfur and selenium containing bis-α-amino acids from 4-hydroxyproline

The synthesis of new substituted prolines carrying at C-4 a second α-amino acid residue is reported. The amino acid, l-cysteine or l-selenocysteine, is linked to the proline ring through the sulfur or the selenium atom, respectively. The products were prepared with different stereochemistry at C-4, in few and clean high-yielding steps, with suitable protections for solid phase applications. The introduction of both sulfur and selenium atoms at C-4 of the proline ring seems to enhance significantly the cis geometry at the prolyl amide bond.

Rationally designed 4-phenoxy substituted prolinamide phenols organocatalyst for the direct aldol reaction in water

A rationally designed 4-phenoxy substituted prolinamide phenols as an efficient hydrophobic organocatalyst for direct asymmetric aldol reaction in water has been developed. High yield (up to 99%), diastereoselectivity (up to 99:1), and enantioselectivity (up to 97%) were obtained under optimal condition. The influence of substituent groups on the reactivity of catalysts was studied in detail. Crown Copyright

Highly diastereo- and enantioselective direct aldol reactions by 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamides in water

A new set of 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamide has been designed and proved to be effective in catalyzing the direct aldol reactions of cyclic ketones with a series of aromatic aldehydes. Furthermore, to the best of our knowledge, there are no reports on the aldol reaction generating the products in very good yields (>99%) and with excellent diastereoselectivities up to >99:1 and enantioselectivities up to >99% by using lower catalyst loadings (only 3 mol %), without using any additives in a large amount of water under mild conditions.