60079-12-1

Upstream product

• 2177-62-0 β-methyl L-aspartate 
• 507-19-7 t-butyl bromide 
• 3160-47-2 N-(benzyloxycarbonyl)-L-aspartic acid 4-methyl ester 
• 123975-50-8 (S)-N-benzyloxycarbonylaspartic acid α-tert-butyl β-allyl ester 
• 99793-10-9 N-benzyloxycarbonyl-L-asparatic acid β-allyl ester 
• 501-53-1 benzyl chloroformate 
• 75-65-0 tert-butyl alcohol 
• 186581-53-3 diazomethane 
• 47307-26-6 (S)-2-benzyloxycarbonylamino-succinic acid 1-tert-butyl ester 
• 115-11-7 isobutene 

Downstream Products

• 123999-77-9 t-butyl 2-benzyloxycarbonylamino-3-carbomethoxy-4-hydroxy-(2S)-hexanoate 
• 123975-54-2 t-butyl 2-benzyloxycarbonylamino-3-carbomethoxy-(2S)-hex-5-enoate 
• 123975-54-2 tert-butyl (2S,3R)-2-(benzyloxycarbonylamino)-3-carbomethoxyhex-5-enoate 
• 228875-01-2 Di-tert-butyl (2S,3R)-2-benzyloxycarbonylamino-3-methoxycarbonylglutarate 
• 177288-58-3 (2S,3R)-Pyrrolidine-1,2,3-tricarboxylic acid 1-benzyl ester 3-methyl ester 
• 175225-10-2 (2S,3R)-2-Allyl-3-benzyloxycarbonylamino-succinic acid 
• 177288-60-7 (2S,3R)-2-Allyl-3-benzyloxycarbonylamino-succinic acid 1-methyl ester 
• 177288-57-2 (2S,3R)-Pyrrolidine-1,2,3-tricarboxylic acid 1-benzyl ester 2-tert-butyl ester 3-methyl ester 
• 177472-11-6 (2S,3R,5R)-5-Hydroxy-pyrrolidine-1,2,3-tricarboxylic acid 1-benzyl ester 2-tert-butyl ester 3-methyl ester 
• 177288-56-1 (2S,3R)-2-Benzyloxycarbonylamino-3-(2-oxo-ethyl)-succinic acid 1-tert-butyl ester 4-methyl ester 
• 177288-59-4 (2S,3S)-Pyrrolidine-1,2,3-tricarboxylic acid 1-benzyl ester 
• 133125-17-4 2(S)-2-(benzyloxycarbonylamino)-4-iodobutyric acid tert-butyl ester 

Relevant academic research and scientific papers

Structure-Guided Design of a "bump-and-Hole" Bromodomain-Based Degradation Tag

Chemical biology tools to modulate protein levels in cells are critical to decipher complex biology. Targeted protein degradation offers the potential for rapid and dose-dependent protein depletion through the use of protein fusion tags toward which protein degraders have been established. Here, we present a newly developed protein degradation tag BRD4BD1L94V along with the corresponding cereblon (CRBN)-based heterobifunctional degrader based on a "bump-and-hole"approach. The resulting compound XY-06-007 shows a half-degradation concentration (DC50, 6 h) of 10 nM against BRD4BD1L94V with no degradation of off-targets, as assessed by whole proteome mass spectrometry, and demonstrates suitable pharmacokinetics for in vivo studies. We demonstrate that BRD4BD1L94V can be combined with the dTAG approach to achieve simultaneous degrader-mediated depletion of their respective protein fusions. This orthogonal system complements currently available protein degradation tags and enables investigation into the consequences resulting from rapid degradation of previously undruggable disease codependencies.

Synthesis of desmosine-containing cyclic peptide for the possible elucidation of elastin crosslinking structure

Elastin is a vital extracellular matrix protein, which is known for providing elasticity in numerous tissues. It is formed by the self-assembly and subsequent crosslinking of elastin precursor, tropoelastin. Two tetrafunctional, pyridinium-based amino acids desmosine and isodesmosine are exclusively found in elastin and play an important role as crosslinkers. Structural elucidation of elastin has eluded scientists to date, owing to the highly cross-linked structure and insoluble nature. Therefore, in this study, we aimed to synthesize a desmosine-containing cyclic peptide as a partial elastin mimic, in order to eventually facilitate the elucidation of the crosslinking pattern of elastin by mass spectrometric analysis.

Design and synthesis of novel P2 substituents in diol-based HIV protease inhibitors

The synthesis and SAR of HIV-1 protease inhibitors containing novel P2 structural elements are presented. The inhibitors were designed having hydrogen bond accepting P2 substituents to probe potential favorable interactions to Asp-29/Asp-30 of the HIV-1 protease backbone utilizing inhibitor 3 as a model template. Several inhibitors were synthesized from an l-Val methyl amide P2 motif by appending hydrogen bonding moieties from either the isopropyl side-chain or from the methyl amide portion. The most promising inhibitors 4a and 4e displayed Ki values of 1.0 nM and 0.7 nM respectively and EC50 values in the MT4 cell-based assay of 0.17 μM and 0.33 μM respectively, a slight loss in potency compared to lead inhibitor 3. These inhibitors were also tested against an HIV protease inhibitor resistant strain carrying the M46I, V82F, and I84V mutations. Inhibitors 4a and 4e displayed a 3 and 4 fold change respectively compared with HIV wild type, whereas lead inhibitor 3 showed a higher 9 fold change. This study further demonstrate the chemical tractability of the approach where various P2 substituents can be introduced in just one chemical step from lactone 21 enabling facile modifications of the overall properties in this inhibitor class.

PYRIMIDINE DERIVATIVES USEFUL AS DHFR INHIBITORS

Compounds of formula (I) or (II) are dihydrofolatereductase inhibitors, useful for the treatment of, for example, cell proliferative diseases: wherein A and D are independently -CHR6- or -NR6; E and G are independently =CR6/sub

Utility of tetrathiomolybdate and tetraselenotungstate: Efficient synthesis of cystine, selenocystine, and their higher homologues

Efficient synthesis of cystine, selenocystine, and their higher homologues like homo and bishomo amino acid derivatives from natural amino acid derivatives using tetrathiomolybdate and tetraselenotungstate reagents under mild and neutral conditions is reported. The generality of the reaction has been studied by capping various groups to amino and carboxyl components of canonical amino acids.

Synthesis and in vitro enzyme activity of aza, oxa and thia derivatives of bacterial cell wall biosynthesis intermediates

Mechanism based inhibitors of diaminopimelate aminotransferase (DAP-AT) were designed using knowledge of its substrate specificity and mechanism. Synthesis of thiolester and amide substrate analogues was achieved prior to in vitro inhibition studies, but ester analogues proved too unstable to isolate. Thia substrate analogues showed no inhibitory properties, but the aza substrate analogue 12a showed reversible inhibition vs. DAP-AT and time dependent inhibition in the absence of the natural substrate 4. Substrate analogue 12a is thefirst example of an amide inhibitor of PLP dependent enzymes. Antibiotic properties of 12a were also briefly assessed.

Glutamyl-γ-boronate inhibitors of bacterial Glu-tRNAGln amidotransferase

Analogues of glutamyl-γ-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNAGln amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of

Non-Proteinogenic Amino Acid Synthesis: Synthesis of β,γ-Unsaturated α-Amino Acids from Aspartic Acid

A general, stereospecific, synthesis of β,γ-unsaturated α-amino acids using the β-anion derived from aspartic acid is described.Keywords: aspartic acid; unsaturated acids

Non-Proteinogenic Amino Acid Synthesis. The β-Anion Derived from Aspartic Acid, and its Application to α-Amino Acid Synthesis.

Treatment of α-t-butyl β-methyl N-Z-(S)-aspartate (2) with lithium amide bases generates the corresponding β-ester enolate, which can be alkylated with suitable electrophiles.The application of this strategy for synthesis of optically active amino acids h

Asymmetric Amino Acid Synthesis: Preparation of the β Anion derived from Aspartic Acid

(S)-1-t-Butyl 4-methyl N-benzyloxycarbonylaspartate (5a), and (S)-1-t-butyl 4-allyl N-benzyloxycarbonylaspartate (5b) have been synthesized from (S)-aspartic acid (2), and can be readily alkylated and hydroxyalkylated at the β-carbon for asymmetric amino acid synthesis.