438239-28-2

Upstream product

• 138797-71-4 (25,3S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(tert-butoxy)butanoic acid 
• 16966-09-9 N-benzyloxycarbonyl-O-t-butyl-L-threonine 
• 52785-41-8 N-benzyloxycarbonyl-O-tert-butylthreonine methyl ester 
• 71989-35-0 Fmoc-Thr(tBu)-OH 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 

Downstream Products

• 1213705-62-4 C₂₃H₂₇NO₄ 
• 301352-10-3 {(1R,2R)-1-[[(3aR,4R,6R,6aR)-6-(6-Benzoylamino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethoxy]-(2-cyano-ethoxy)-phosphoryloxymethyl]-2-tert-butoxy-propyl}-carbamic acid 9H-fluoren-9-ylmethyl ester 

Relevant academic research and scientific papers

Urea based foldamers

N,N′-linked oligoureas are a class of enantiopure, sequence-defined peptidomimetic oligomers without amino acids that form well-defined and predictable helical structures akin to the peptide α-helix. Oligourea-based foldamers combine a number of features—such as synthetic accessibility, sequence modularity, and folding fidelity—that bode well for their use in a range of applications from medicinal chemistry to catalysis. Moreover, it was recently recognized that this synthetic helical backbone can be combined with regular peptides to generate helically folded peptide-oligourea hybrids that display additional features in terms of helix mimicry and protein-surface recognition properties. Here we provide detailed protocols for the preparation of requested monomers and for the synthesis and purification of homo-oligoureas and peptide-oligourea hybrids.

POLYMYXIN-BASED COMPOUNDS USEFUL AS ANTIBACTERIAL AGENTS

It relates to polymyxin analogues having a disulfide bond and an amino alcohol group adjacent to the disulfide bond, and optionally, an ester bond in the peptide backbone, which are useful as antibacterial agent, as well as to pharmaceutical compositions comprising them. It also relates to a key intermediate compound of formula (II) and its preparation process.

Staudinger/aza-Wittig reaction to access Nβ-protected amino alkyl isothiocyanates

A unified approach to access Nβ-protected amino alkyl isothiocyanates using Nβ-protected amino alkyl azides through a general strategy of Staudinger/aza-Wittig reaction is described. The type of protocol used to access isothiocyanates depends on the availability of precursors and also, especially in the amino acid chemistry, on the behavior of other labile groups towards the reagents used in the protocols; fortunately, we were not concerned about both these factors as precursor-azides were prepared easily by standard protocols, and the present protocol can pave the way for accessing title compounds without affecting Boc, Cbz and Fmoc protecting groups, and benzyl and tertiary butyl groups in the side chains. The present strategy eliminates the need for the use of amines to obtain title compounds and thus, this method is step-economical; additional advantages include retention of chirality, convenient handling and easy purification. A few hitherto unreported compounds were also prepared, and all final compounds were completely characterized by IR, mass, optical rotation, and 1H and 13C NMR studies.

Synthesis method of Fmoc-O-tert-butyl-L-threoninol

The present invention relates to a synthesis method of Fmoc-O-tert-butyl-L-threoninol, and mainly solves the technical problems that in a process of Fmoc-thr(tbu)-oh reduction by sodium borohydride, the reaction temperature is strictly required and a FMoc protecting group is decomposed, resulting in low yield and high cost. The synthesis method of the invention comprises the following steps: a. L-threonine reacts with thionyl chloride to form L-threonine methyl ester hydrochloride; b. the L-threonine methyl ester hydrochloride under the action of sodium hydroxide is reacted with benzyl chloroformate to produce z-thr-ome; c. the Z-thr-ome reacts with introduced isobutene in the presence of methylene chloride and concentrated sulfuric acid, and alkali adjustment treatment is carried out to obtain z-thr (tbu)-ome; d. in the presence of acetone and water, the Z-thr(tbu)-ome is saponified with added alkali to obtain z-thr(tbu)-oh; e. the Z-thr(tbu)-oh is reduced to z-thr(tbu)-ol by sodium borohydride in tetrahydrofuran; f. the z-thr(tbu)-ol is hydrogenated in methanol to obtain H-thr(tbu)-ol; and g. N-(9-fluorenylmethoxycarbonyloxy)succinimide is added to the H-thr(tbu)-ol to obtain the Fmoc-O-tert-butyl -L-threoninol.

3-PYRIMIDIN-4-YL-OXAZOLIDIN-2-ONES AS INHIBITORS OF MUTANT IDH

The invention is directed to a formula (I), or a pharmamceutically acceptable salt thereof, wherein R1, R2a, R2b and R3-R7 are herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

A facile synthesis and crystallographic analysis of N-protected β-amino alcohols and short peptaibols

A facile, efficient and racemization-free method for the synthesis of N-protected β-amino alcohols and peptaibols using N-hydroxysuccinimide active esters is described. Using this method, dipeptide, tripeptide and pentapeptide alcohols were isolated in high yields. The conformations in crystals of β-amino alcohol, dipeptide and tripeptide alcohols were analysed, with a well-defined type III β-turn being observed in the tripeptide alcohol crystals. This method is found to be compatible with Fmoc-, Boc- and other side-chain protecting groups.

Synthesis of peptide alcohols on the basis of an O-N acyl-transfer reaction

(Figure Presented) Getting the better of troublemakers: C-terminal peptide alcohols cannot be synthesized by conventional solidphase peptide synthesis (SPPS) because of the absence of a free carboxylic group to attach to the resin. This problem was circumvented by anchoring a β-amino alcohol residue to the resin to provide a starting point for SPPS. An intramolecular O-N acyl shift completed the synthesis of the desired peptides (see scheme).

Structure-affinity relationships of glutamine mimics incorporated into phosphopeptides targeted to the SH2 domain of signal transducer and activator of transcription 3

In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gln mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC50 values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4- methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC50 of 69 nM, the highest affinity Stat3 inhibitor reported to date. 2009 American Chemical Society.

Solid phase method for synthesis peptide-spacer-lipid conjugates, conjugates synthesized thereby and targeted liposomes containing the same

A solid phase synthesis method for preparing peptide-spacer-lipid conjugates, the peptide-spacer-lipid conjugates synthesized by the method, and liposomes containing the peptide-spacer-lipid conjugates. The present invention provides a convenient solid phase synthesis method for preparing peptide-spacer-lipid conjugates and provides various linkage groups (such as amide group) for conjugating peptide, spacer and lipid, wherein the spacer may comprise PEG. Several advantages can be achieved, such as the synthetic procedure can be simplified, the synthesis process can be set to automation, the purification is easier in each reaction step, and the product losses can be reduced to minimal during synthesis. The present synthesis method is suitable for preparing a wide range of peptide-spacer-lipid conjugates, provides a peptide-spacer-lipid conjugate prepared by the solid phase synthesis method of the present invention, which can be incorporated into a liposome as the targeting moiety for liposomal drug delivery to specific cells, and provides a targeting liposome containing the present peptide-spacer-lipid conjugate.

Solid phase method for synthesis peptide-spacer-lipid conjugates, conjugates synthesized thereby and targeted liposomes containing the same

A solid phase synthesis method for preparing peptide-spacer-lipid conjugates, the peptide-spacer-lipid conjugates synthesized by the method, and liposomes containing the peptide-spacer-lipid conjugates. The present invention provides a convenient solid phase synthesis method for preparing peptide-spacer-lipid conjugates and provides various linkage groups (such as amide group) for conjugating peptide, spacer and lipid, wherein the spacer may comprise PEG. Several advantages can be achieved, such as the synthetic procedure can be simplified, the synthesis process can be set to automation, the purification is easier in each reaction step, and the product losses can be reduced to minimal during synthesis. The present synthesis method is suitable for preparing a wide range of peptide-spacer-lipid conjugates, provides a peptide-spacer-lipid conjugate prepared by the solid phase synthesis method of the present invention, which can be incorporated into a liposome as the targeting moiety for liposomal drug delivery to specific cells, and provides a targeting liposome containing the present peptide-spacer-lipid conjugate.