113775-22-7

Usage

Uses

Used in Organic Synthesis:
BOC-4-HYDROXY-L-PYRROLIDINE LACTONE is used as a building block in organic synthesis for the preparation of a variety of pharmaceuticals and fine chemicals. Its unique structure and functional groups contribute to the creation of diverse chemical entities with potential applications in the pharmaceutical industry.
Used in Pharmaceutical Industry:
BOC-4-HYDROXY-L-PYRROLIDINE LACTONE is utilized as a key intermediate in the synthesis of drugs and pharmaceutical compounds. Its presence in the synthesis process is crucial for the development of new and innovative medications, enhancing the therapeutic options available to patients.
Used in the Production of Pharmaceutical Products:
Due to its versatile reactivity and functional groups, BOC-4-HYDROXY-L-PYRROLIDINE LACTONE is a valuable compound for the production of a wide range of pharmaceutical products. Its role in the synthesis of these products is essential for meeting the demands of the healthcare sector and improving patient outcomes.

InChI:InChI=1/C10H15NO4/c1-10(2,3)15-9(13)11-5-6-4-7(11)8(12)14-6/h6-7H,4-5H2,1-3H3/t6-,7-/m0/s1

Upstream product

• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 202477-59-6 (2S,4R)-1-(tert-butoxycarbonyl)-4-[(methylsulfonyl)oxy]-2-pyrrolidinecarboxylic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 51-35-4 4R-4-hydroxyproline 
• 1972-28-7 diethylazodicarboxylate 
• 1332341-02-2 benzyl (2S)-2-Boc-amino-3-(2-oxiranyl)propionate 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 

Downstream Products

• 74844-91-0 (2S,4S)-N-tert-butoxycarbonyl-4-hydroxyproline methyl ester 
• 40350-83-2 (2S,4S)-4-(benzyloxy)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid 
• 121148-00-3 1-(1,1-dimethylethyl) 2-methyl (2S,4R)-4-amino-1,2-pyrrolidinedicarboxylate 
• 438452-29-0 1-tert-butyl 2-methyl (2S,4S)-4-{[(4-bromo-phenyl)sulfonyl]oxy}-pyrrolidine-1,2-dicarboxylate 
• 1229626-28-1 (2R,6R,14aR,16aS,Z)-N-(cyclopropylsulfonyl)-6-(2-(3,3-difluoropiperidin-1-yl)-2-oxoethyl)-2-(2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxamide 
• 1252637-02-7 (2S,4R)-4-(4-fluoro-2-trifluoromethylbenzenesulfonyl)-1-(1-trifluoromethylcyclopropanecarbonyl)pyrrolidine-2-carboxylic acid (1-cyanocyclopropyl)amide 

Relevant academic research and scientific papers

Solid-phase synthesis of a novel phalloidin analog with on-bead and off-bead actin-binding activity

Specific effectors of actin polymerization have found use as dynamic probes of cellular morphology that may be used to gauge cellular response to stimuli and drugs. Of various natural products that target actin, phalloidin is one of the most potent and selective inhibitors of actin depolymerization. Phalloidin and related members of the phallotoxin family are macrocyclic heptapeptides bearing a characteristic and rigidifying transannular tryptathionine bridge. Here we describe a solid-phase synthesis of a new phalloidin analog as a prototype for library development with the potential for on- and off-bead screening. To validate our method, we labelled the phalloidin derivative with a fluorescent dye which stained actin in CHO cells. Furthermore, a bioassay was developed allowing actin polymerization on beads carrying a phalloidin derivative.

Aza-wittig-supported synthesis of the a ring of nosiheptide

An array of aza-Wittig reactions: In the unique synthesis of the A ring of the potent thiopeptide antibiotic nosiheptide, mild aza-Wittig thiazole ring closure, a ScIII-mediated regioselective ester hydrolysis, and a highly efficient macrolactam formation

Design, Synthesis, and Biochemical Evaluation of Alpha-Amanitin Derivatives Containing Analogs of the trans-Hydroxyproline Residue for Potential Use in Antibody-Drug Conjugates

Alpha-amanitin, an extremely toxic bicyclic octapeptide extracted from the death-cap mushroom, Amanita phalloides, is a highly selective allosteric inhibitor of RNA polymerase II. Following on growing interest in using this toxin as a payload in antibody-drug conjugates, herein we report the synthesis and biochemical evaluation of several new derivatives of this toxin to probe the role of the trans-hydroxyproline (Hyp), which is known to be critical for toxicity. This structure activity relationship (SAR) study represents the first of its kind to use various Hyp-analogs to alter the conformational and H-bonding properties of Hyp in amanitin.

Automated Radiosynthesis of cis- And trans-4-[18F]Fluoro- l -proline Using [18F]Fluoride

The positron emission tomography imaging agents cis- and trans-4-[18F]fluoro-l-proline are used for the detection of numerous diseases such as pulmonary fibrosis and various carcinomas. These imaging agents are typically prepared by nucleophilic fluorination of 4-hydroxy-l-proline derivatives, with [18F]fluoride, followed by deprotection. Although effective radiofluorination reactions have been developed, the overall radiosynthesis process is suboptimal due to deprotection methods that are performed manually, require multiple steps, or involve harsh conditions. Here we describe the development of two synthetic routes that allow access to precursors, which undergo highly selective radiofluorination reactions and rapid deprotection, under mild acidic conditions. These methods were found to be compatible with automation, avoiding manual handling of radioactive intermediates.

cis-4-Alkoxydialkyl- and cis-4-Alkoxydiarylprolinol Organocatalysts: High Throughput Experimentation (HTE)-Based and Design of Experiments (DoE)-Guided Development of a Highly Enantioselective aza-Michael Addition of Cyclic Imides to α,β-Unsaturated Aldehydes

A diverse family (37 compounds) of cis-4-alkoxydiorganylprolinol derivatives has been prepared and evaluated in organocatalysis for the first time. The combined use of high throughput experimentation (HTE) techniques with efficient analytical methods has led to the identification of two superior catalysts for the enantioselective addition of succinimide to α,β-unsaturated aldehydes. Further optimization of the reaction conditions with design of experiments (DoE) techniques established the catalyst of choice for the considered aza-Michael reaction, the corresponding adducts (12 examples) being obtained in good yields and excellent enantioselectivities (succinimide and maleimide donors). The synthetic versatility of these Michael adducts is illustrated by a two-step sequence leading to enantiopure 1,3-amino alcohols. (Figure presented.).

Synthesis of (1R,4R)-2,5-diazabicyclo[2.2.1]heptane derivatives by an epimerization-lactamization cascade reaction

An epimerization-lactamization cascade of functionalized (2S,4R)-4-aminoproline methyl esters is developed and applied in synthesizing (1R,4R)-2,5-diazabicyclo[2.2.1]heptane (DBH) derivatives. (2S,4R)-4-Aminoproline methyl esters are likely to undergo 2-epimerization under basic conditions, followed by an intramolecular aminolysis of the (2R)-epimer to form the bridged lactam intermediates. Key factors identified for this cascade reaction include the electron-withdrawal N-protective group in the substrates and a strong base as the promoter.

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.

Assembly of the nosiheptide A-ring: A fruitful lesson

The synthesis of a 28-membered thiopeptide macrocycle is described. Key steps are mild aza-Wittig thiazole ring closures, a scandium(III)-mediated regioselective ester hydrolysis, and a highly efficient macrolactam formation with its 3-hydroxypyridine nucleus orthogonally protected. Georg Thieme Verlag Stuttgart, New York.

Solid-phase synthesis of smac peptidomimetics incorporating triazoloprolines and biarylalanines

Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural clues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide-alkyne cycloaddition and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.

ANTIBACTERIAL FLUOROQUINOLONE ANALOGS

Compounds having antibacterial activity are disclosed. The compunds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein A, B, D, E, G, R1, R2, R3, R4, R5, R6 and R7 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.