215596-38-6

Upstream product

• 1080-06-4 L-Tyr-OMe 
• 541-41-3 chloroformic acid ethyl ester 
• 3417-91-2 L-tyrosine methyl ester HCl 
• 60-18-4 L-tyrosine 

Downstream Products

• 385842-97-7 (S)-2-amino-N-ethoxycarbonyl-3-(4-hydroxyphenyl)-propanol 
• 726181-69-7 (S)-3-(4-hydroxy-3-nitrophenyl)-2-[(ethoxycarbonyl)amino]-1-propanoic acid methyl ester 
• 215596-40-0 ethoxycarbonyl-L-tyrosine cyclohexyl-ammonium salt 
• 187332-12-3 (4S)-4-(4-hydroxybenzyl)-1,3-oxazolidin-2-one 
• 849041-79-8 (S)-2-Ethoxycarbonylamino-3-[4-(4-methoxy-benzyloxy)-phenyl]-propionic acid methyl ester 
• 442128-78-1 methyl (2S)-3-(4-benzyloxyphenyl)-2-ethoxycarbonylaminopropionate 
• 442129-00-2 methyl N-[(2S)-3-(4-benzyloxyphenyl)-2-(tert-butoxycarbonylmethylamino)propyl]aminoacetate 
• 442128-91-8 1,1-dimethylethyl N-[(1S)-2-hydroxy-1-{[4-(phenylmethoxy)phenyl]methyl}ethyl]-N-methylcarbamate 
• 442129-04-6 methyl N-[(2S)-3-(4-benzyloxyphenyl)-2-methylaminopropyl]aminoacetate 
• 442128-96-3 (1S)-3-(4-benzyloxyphenyl)-2-[(N)-tert-butoxycarbonyl]methylaminopropanal 
• 442129-08-0 (6S)-6-(4-benzyloxybenzyl)-1-methylpiperazin-2-one 
• 442128-85-0 (S)-N-(1-(4-(benzyloxy)phenyl)-3-hydroxypropan-2-yl)-N-methylamine 
• 442129-12-6 (6S)-6-(4-hydroxybenzyl)-1-methylpiperazin-2-one 
• 726181-70-0 Fmoc-3-amino-L-tyrosine 

Relevant academic research and scientific papers

Discovery of a novel nonphosphorylated pentapeptide motif displaying high affinity for Grb2-SH2 domain by the utilization of 3′-substituted tyrosine derivatives

The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. An impressive number of synthetic Grb2-SH2 domain inhibitors have been identified; however, clinical agents operating by this mechanism are lacking, due in part to the unique requirement of anionic phosphate-mimicking functionality for high SH2 domain-binding affinity or the extended peptide nature of most inhibitors. In the current study, a new binding motif was successfully developed by the incorporation of 3′-substituted tyrosine derivatives into a simplified nonphosphorylated cyclic pentapeptide scaffold (4), which resulted in high affinity Grb2-SH2 inhibitors without any phosphotyrosine or phosphotyrosine mimetics. The new L-amino acid analogues bearing an additional nitro, amino, hydroxy, methoxy or carboxy group at the 3′-position of the phenol ring of tyrosine were prepared in an orthogonally protected form suitable for solid-phase peptide synthesis using Fmoc protocols. The incorporation of these residues into cyclic peptides composed of a five-amino acid sequence motif, Xx′-Leu-(3′- substituted-Tyr)-Ac6c-Asn, provided a brand new class of nonphosphorylated Grb2 SH2 domain inhibitors with reduced size, charge and peptidic character. The highest binding affinity was exhibited by the 3′-aminotyrosine (3′-NH2-Tyr)-containing (R)-sulfoxide-cyclized pentapeptide (10b) with an IC50 = 58 nM, the first example with low-nanomolar affinity for a five-amino acid long sequence binding to Grb2-SH2 domain free of any phosphotyrosine or phosphotyrosine mimics. However, the incorporation of 3′-NO2-Tyr, 3′-OH-Tyr or 3′-OCH3-Tyr surrogates in the pentapeptide scaffold is detrimental to Grb2-SH2 binding. These observations were rationalized using molecular modeling. More significantly, the best Grb2-SH2 inhibitor 10b showed excellent activity in inhibiting the growth of erbB2-dependent MDA-MB-453 tumor cell lines with an IC50 value of 19 nM. This study is the first attempt to identify novel nonphosphorylated high affinity Grb2 SH2 inhibitors by the utilization of 3′-substituted tyrosine derivatives, providing a promising new strategy and template for the development of non-pTyr-containing Grb2-SH2 domain antagonists with potent cellular activity, which potentially may find value in chemical therapeutics for erbB2-related cancers.

Development of L-3-aminotyrosine suitably protected for the synthesis of a novel nonphosphorylated hexapeptide with low-nanomolar Grb2-SH2 domain-binding affinity

Synthesis of orthogonally protected (2S)-2-amino-3-(3-amino-4-hydroxy- phenyl)-propionic acid (10) suitable for solid phase peptide synthesis and its first use for the preparation of nonphosphorylated Grb2-SH2 domain antagonists (4a-c) are reported. The 3-aminotyrosine containing sulfoxide-cyclized hexapeptide (4b) exhibited potent Grb2-SH2 domain binding affinity with IC 50=50nM, which represents the highest affinity yet reported for a peptide inhibitor against Grb2-SH2 domain with only 6 residues free of phosphotyrosine or phosphotyrosine mimics. This potent small peptidomimetic 4b may be representative of a new class of therapeutically relevant Grb2-SH2 domain-directed agents, and acts as a chemotherapeutic lead for the treatment of erbB2-related cancers.

A formal synthesis of a muscarinic M1 receptor antagonist, (-)-TAN1251A

An aromatic oxidation reaction of a secondary amine, prepared from L-tyrosine and glycine, with hypervalent iodine reagent gave a spirocyclic product, which was further converted into the key intermediate for the synthesis of (-)-TAN1251A.

Synthesis of Carbamates Using Yttria-Zirconia Based Lewis Acid Catalyst

A variety of amines react with chloroformates in the presence of catalytic amount of yttria-zirconia based catalyst to afford the corresponding carbamates in excellent yields.

Facile synthesis of enantiopure (-)-TAN1251A

Formal total synthesis of enantiopure (-)-TAN1251A, a muscarinic M1 receptor antagonist, was achieved via a spirocyclic carbon-nitrogen bond formation by the use of aromatic oxidation with bis(acetoxy)iodobenzene as a key step.

Solid supported chiral auxiliaries in asymmetric synthesis. Part 2: Catalysis of 1,3-dipolar cycloadditions by Mg(II) cation

1,3-Dipolar cycloadditions of supported Evans' chiral auxiliary with nitrile oxides and nitrones in the presence of Mg(II) cation as catalyst were evaluated. The presence of acetonitrile as co-solvent was found to be fundamental for the Lewis acid catalysis on solid-phase. The regio- and stereochemical outcome of nitrile oxide cycloadditions is influenced by nearly stoichiometric quantities of the cation, whilst catalytic amounts of Mg(II) influence both the reactivity and the stereoselectivity of the nitrone cycloadditions. The results obtained support a reaction mechanism involving the coordination of the Mg(II) to the dicarbonyl fragment of the chiral auxiliary.

(4S)-p-hydroxybenzyl-1,3-oxazolidin-2-one as a solid-supported chiral auxiliary in asymmetric 1,3-dipolar cycloadditions

Evans' chiral auxiliary was grafted onto both Merrifield and Wang resins and, after functionalisation, they were used as chiral dipolarophiles in a 1,3-dipolar cycloaddition involving both a nitrile oxide and a nitrone. The cycloadducts were cleaved and analysed by chiral HPLC: the recovered supported chiral oxazolidinone was functionalised and reused in further cycloadditions. The stereochemical results as well as the possibility of recycling the chiral linker supports the applicability of solid-supported chiral auxiliaries. (C) 2000 Elsevier Science Ltd.