135923-86-3

Upstream product

• 113806-26-1 sodium benzylidene-D-alanilate 
• 501-53-1 benzyl chloroformate 
• 1125-88-8 benzaldehyde dimethyl acetal 
• 26607-51-2 N-benzyloxycarbonyl-D-alanine 
• 100-52-7 benzaldehyde 
• 1142-20-7 N-Cbz-Ala 
• 113806-26-1 Sodium; (S)-2-{[1-phenyl-meth-(E)-ylidene]-amino}-propionate 

Downstream Products

• 143564-90-3 (2R,4R)-4-Benzylsulfanylmethyl-4-methyl-5-oxo-2-phenyl-oxazolidine-3-carboxylic acid benzyl ester 
• 519020-85-0 (R)-4-iodomethyl-4-methyl-5-oxo-2-phenyloxazolidine-3-carboxylic acid benzyl ester 
• 519020-70-3 (R)-4-chloromethyl-4-methyl-5-oxo-2-phenyloxazolidine-3-carboxylic acid benzyl ester 
• 519021-00-2 (R)-4-methyl-4-methylsulfanylmethyl-5-oxo-2-phenyloxazolidine-3-carboxylic acid benzyl ester 
• 537040-12-3 (2R,4S)-2-phenyl-3-(carbobenzyloxy)-4-methyl-4-[(3-methoxy)carbonyl-(1E)-propenyl]oxazolidin-5-one 
• 537040-14-5 (2S,3S,4S)-N-carbobenzyloxy-2-methyl-2-(carboxycyclopropyl)glycine 
• 519020-80-5 (S)-1-benzyloxycarbonyl-2-methylaziridine-2-carboxylic acid methyl ester 
• 519020-76-9 (R)-2-benzyloxycarbonylamino-3-chloro-2-methylpropionic acid 
• 519020-71-4 (R)-2-benzyloxycarbonylamino-3-chloro-2-methylpropionic acid methyl ester 
• 519021-01-3 (R)-2-benzyloxycarbonylamino-2-methyl-3-methylsulfanylpropionic acid methyl ester 
• 519020-86-1 (R)-2-benzyloxycarbonylamino-3-iodo-2-methylpropionic acid methyl ester 
• 519021-06-8 (R)-2-benzyloxycarbonylamino-3-(4-chlorophenylsulfanyl)-2-methylpropionic acid methyl ester 
• 519020-79-2 (R)-2-(1-benzyloxycarbonylamino-2-chloro-1-methylethyl)-5-methyloxazole-4-carboxylic acid methyl ester 
• 519020-78-1 (R)-2-(2-benzyloxycarbonylamino-3-chloro-2-methylpropionylamino)-3-oxobutyric acid methyl ester 

Relevant academic research and scientific papers

Stereoselective Synthesis of (R)-3-Methylthalidomide by Piperidin-2-one Ring Assembly Approach

A simple and stereoselective synthesis of 3-methylthalidomide, a configurationally stable thalidomide analog, is presented. Herein we describe the synthesis of (R)-3-methylthalidomide starting from (S)-alanine by piperidin-2-one ring assembly approach in high yield and enantiomeric purity without using a chiral auxiliary or reagent. Starting from (R)-alanine, the corresponding (S)-3-methylthalidomide can be prepared using the same methodology. Chirality 27:619-624, 2015.

COVALENT RAS INHIBITORS AND USES THEREOF

The disclosure features compounds, or pharmaceutically acceptable salts thereof, alone and in combination with other therapeutic agents, pharmaceutical compositions, and protein conjugates thereof, capable of modulating biological processes including Ras, and their uses in the treatment of cancers.

RAS INHIBITORS

The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.

Method for preparing 2-methylserine

The invention relates to a method for preparing 2-methylserine, and mainly solves the technical problem of being long in route, complicated in operation, and not conducive to mass production of the existing synthetic method. The method comprises the following steps: Cbz-chiral alanine and Benzaldehyde dimethyl acetal are reacted under the action of thionyl chloride and zinc chloride, a reaction product is crystallized to obtain an intermediate 1, the intermediate 1 is reacted under cooperation of an alkaline reagent to obtain an intermediate 2, an intermediate 3 is obtained from the intermediate 2 by the action of lithium hydroxide, and the final product 2-methylserine is obtained from the intermediate 3 by palladium carbon catalytic hydrogenolysis. High purity 2-methylserine can be obtained by the method.

Synthesis of 4-hydroxy-2-methylproline derivatives via pyrrolidine ring assembly: chromatographic resolution and diastereoselective synthesis approaches

4-Hydroxy-2-methylproline diastereomers are successfully prepared without the use of an external chiral auxiliary. Dihydroxylation of the key intermediate 2 resulted in lactone 4 as a mixture of diastereomers in good yield. Mesylation, hydrogenation and c

Design of cell-permeable stapled peptides as HIV-1 integrase inhibitors

HIV-1 integrase (IN) catalyzes the integration of viral DNA into the host genome, involving several interactions with the viral and cellular proteins. We have previously identified peptide IN inhibitors derived from the α-helical regions along the dimeric interface of HIV-1 IN. Herein, we show that appropriate hydrocarbon stapling of these peptides to stabilize their helical structure remarkably improves the cell permeability, thus allowing inhibition of the HIV-1 replication in cell culture. Furthermore, the stabilized peptides inhibit the interaction of IN with the cellular cofactor LEDGF/p75. Cellular uptake of the stapled peptide was confirmed in four different cell lines using a fluorescein-labeled analogue. Given their enhanced potency and cell permeability, these stapled peptides can serve as not only lead IN inhibitors but also prototypical biochemical probes or nanoneedles for the elucidation of HIV-1 IN dimerization and host cofactor interactions within their native cellular environment.

Biaryl-bridged macrocyclic peptides: Conformational constraint via carbogenic fusion of natural amino acid side chains

A general method for constraining peptide conformations via linkage of aromatic sidechains has been developed. Macrocyclization of suitably functionalized tri-, tetra- and pentapeptides via Suzuki-Miyaura cross-coupling has been used to generate side chain to side chain, biaryl-bridged 14- to 21-membered macrocyclic peptides. Biaryl bridges possessing three different configurations, meta-meta, meta-ortho, and ortho-meta, were systematically explored through regiochemical variation of the aryl halide and aryl boronate coupling partners, allowing fine-tuning of the resultant macrocycle conformation. Suzuki-Miyaura macrocyclizations were successfully achieved both in solution and on solid phase for all three sizes of peptide. This approach constitutes a means of constraining peptide conformation via direct carbogenic fusion of side chains of naturally occurring amino acids such as phenylalanine and tyrosine, and so is complementary to strategies involving non-natural, for example, hydrocarbon, bridges.

Synthesis and utilization of chiral α-methylated α-amino acids with a carboxyalkyl side chain in the design of novel Grb2-SH2 peptide inhibitors free of phosphotyrosine

The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. To improve the potency and bioavailability of the Grb2-SH2 inhibitors, the chiral α-methyl-α-carboxyalkyl amino acid [(α-Me)Aa] was designed to cover dual structural and functional features separately contributed by 1-aminocyclohexanecarboxylic acid (Ac6c) and α-aminoadipic acid (Adi) in position Y + 1. The enantiopure L(or D)-(α-Me)Aa bearing various chain length carboxylalkyl side chain was conveniently synthesized by an optimized oxazolidinone methodology. The incorporation of (S)-(α-Me)Aa into the non-pTyr-containing peptide framework with a 5-amino acid sequence binding motif of X-2-Leu- (3′-substituted-Tyr)0-X+1-Asn really improved the inhibitory activity, affording potent (R)-sulfoxide-bridged cyclic and an open-chain series of pentapeptide inhibitors of Grb2-SH2 domain (IC50 = 1.1-5.8 μM). More significantly, these (α-Me)Aa incorporated peptide inhibitors showed excellent activities in inhibiting the growth of erbB2-dependent MDA-MB-453 tumor cell lines with low micromolar IC50 values, owing to the reduced peptidic nature and absence of pTyr or pTyr mimetics.

SULFUR COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE

The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

Potassium trimethylsilanolate induced cleavage of 1,3-oxazolidin-2- and 5-ones, and application to the synthesis of (R)-salmeterol.

A convenient and efficient method for the cleavage of 1,3-oxazolidin-5-ones and 1,3-oxazolidin-2-ones utilising potassium trimethylsilanolate in tetrahydrofuran is described. The benzyloxycarbonyl-protecting group is readily removed under the reaction conditions, whereas the N-benzoyl group is stable. A synthesis of (R)-salmeterol exploiting the 2-oxazolidinone ring as a protecting group for the ethanolamine moiety is also described.