84111-38-6

Upstream product

• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 21760-98-5 L-valine benzyl ester 
• 2462-34-2 L-valine benzyl ester hydrochloride 
• 100-51-6 benzyl alcohol 
• 16652-76-9 L-valine benzyl ester p-toluenesulfonate salt 

Downstream Products

• 84111-39-7 L-leucyl-L-valine benzyl ester 
• 84111-40-0 L-leucyl-L-valine benzyl ester TFA salt 

Relevant academic research and scientific papers

Paclitaxel micelle based on (S)-2-decanoylamino-3-(1-naphthyl) propionyl-leucyl-valine

The invention provides a paclitaxel micelle based on (S)-2-decanoylamino-3-(1-naphthyl) propionyl-leucyl-valine. The paclitaxel micelle comprises the (S)-2-decanoylamino-3-(1-naphthyl) propionyl-leucyl-valine and paclitaxel. In the paclitaxel micelle based on (S)-2-decanoylamino-3-(1-naphthyl) propionyl-leucyl-valine, the paclitaxel micelle based on (S)-2-decanoylamino-3-(1-naphthyl) propionyl-leucyl-valine has a carboxyl aliphatic chain, can increase the intracellular property of an active drug, and has the effects of reversing the drug resistance of an anti-tumor drug, resisting tumor cell migration and resisting tumor cell invasion after being prepared into micelles with the paclitaxel.

Fluorescence traceable amino acid derivative and preparation method and application thereof

The invention provides a fluorescence traceable amino acid derivative and a preparation method and application thereof, and belongs to the technical field of biological medicines. According to the amino acid derivative provided by the invention, an amino acid skeleton is modified by mainly adopting a functional group capable of realizing fluorescence tracing, the NBD-Cl (4-chloro-7-nitro-2, 1, 3-benzoxaoxadiazole) has the characteristics of low polarity and strong fluorescence, can be used for subcellular imaging by modifying the N end of an amino acid skeleton with the NBD-Cl, and has the advantages of small relative volume, lack of reaction orthogonality and small interference on the biochemical reaction of organisms. Results of the embodiment show that the amino acid derivative capableof being subjected to fluorescence tracing is good in biological activity and can be subjected to fluorescence tracing in vitro and vivo.

Design, synthesis, and evaluation of cystargolide-based β-lactones as potent proteasome inhibitors

The peptidic β-lactone proteasome inhibitors (PIs) cystargolides A and B were used to conduct structure-activity relationship (SAR) studies in order to assess their anticancer potential. A total of 24 different analogs were designed, synthesized and evaluated for proteasome inhibition, for cytotoxicity towards several cancer cell lines, and for their ability to enter intact cells. X-ray crystallographic analysis and subunit selectivity was used to determine the specific subunit binding associated with the structural modification of the β-lactone (P1), peptidic core, (Px and Py), and end-cap (Pz) of our scaffold. The cystargolide derivative 5k, structurally unique at both Py and P1, exhibited the most promising inhibitory activity for the β5 subunit of human proteasomes (IC50 = 3.1 nM) and significant cytotoxicity towards MCF-7 (IC50 = 416 nM), MDA-MB-231 (IC50 = 74 nM) and RPMI 8226 (IC50 = 41 nM) cancer cell lines. Cellular infiltration assays revealed that minor structural modifications have significant effects on the ability of our PIs to inhibit intracellular proteasomes, and we identified 5k as a promising candidate for continued therapeutic studies. Our novel drug lead 5k is a more potent proteasome inhibitor than carfilzomib with mid-to-low nanomolar IC50 measurements and it is cytotoxic against multiple cancer cell lines at levels approaching those of carfilzomib.

N-linked peptidoresorc[4]arene-based receptors as noncompetitive inhibitors for α-chymotrypsin

This paper deals with the design, synthesis, and evaluation of a new series of receptors for protein surface recognition. The design of these agents is based around the attachment of four constrained dipeptide chains onto a central resorc[4]arene scaffold. By varying the sequence, nature, and stereochemistry of the chains we prepared anionically functionalized N-linked peptidoresorc[4] arenes 12, 13, and 17 by Pd/C-catalyzed hydrogenation of the corresponding benzyl esters 10, 11, and 16. From this family of receptors we have identified noncompetitive inhibitors of α-chymotrypsin (ChT), which function by binding to the surface of the enzyme in the neighborhood of the active site cleft (Ki values ranging from 12.4 ± 5.1 μM for free carboxylic acid (+)-12b to 0.76 ± 0.14 μM for benzyl ester (-)-16a). For anionically functionalized receptors 12, 13, and 17 the ChT inhibition is based essentially on electrostatic interaction, and the bound enzyme can be released from the resorcarene surface by increasing the ionic strength, with its activity almost completely restored. For receptors with terminal benzyl ester groups (10 and 16) a hydrophobic network can be suggested.

Total synthesis of the antimitotic bicyclic peptide celogentin C

An account of the total synthesis of celogentin C is presented. A right-to-left synthetic approach to this bicyclic octapeptide was unsuccessful due to an inability to elaborate derivatives of the right-hand ring. In the course of these efforts, it was discovered that the mild Braslau modification of the McFadyen-Stevens reaction offers a useful method of reducing recalcitrant esters to aldehydes. A leftto-right synthetic strategy was then examined. The unusual Leu-Trp side-chain cross-link present in the left-hand macrocycle was fashioned via a three-step sequence comprised of an intermolecular Knoevenagel condensation, a radical conjugate addition, and a SmI2-mediated nitro reduction. A subsequent macrolactamization provided the desired ring system. The high yield and concise nature of the left-hand ring synthesis offset the modest diastereoselectivity of the radical conjugate addition. Formation of the Trp-His sidechain linkage characteristic of the right-hand ring was then accomplished by means of an indole-imidazole oxidative coupling. Notably, Pro-OBn was required as an additive in this reaction. Detailed mechanistic investigations indicated that Pro-OBn moderates the concentration of NCS in the reaction mixture, thereby minimizing the production of an undesired dichlorinated byproduct. The natural product was obtained after macrolactamization and deprotection. The chemical shifts of the imidazole hydrogen atoms exhibited significant dependence on temperature, concentration, and pH. Antitumor screening indicated that celogentin C inhibits the growth of some cancer cell lines.