40916-80-1

Upstream product

• 5856-63-3 (2R)-2-aminobutan-1-ol 
• 100-52-7 benzaldehyde 

Downstream Products

• 6257-49-4 (2R)-2-(benzylamino)butan-1-ol 
• 1329682-33-8 (5R,15R)-6,14-dibenzyl-5,15-diethyl-3,17-dioxa-6,14,23,24-tetraazatricyclo[17.3.1.1(8,12)]tetracosa-1⁽²³⁾,8,10,12⁽²⁴⁾19,21-hexaene 
• 1258208-16-0 (2R)-2-{benzyl[(6-[[benzyl-(2R)-(1-hydroxybutan-2-yl)amino]methyl]pyridin-2-yl)methyl]amino}-butan-1-ol 
• 1227918-14-0 [(2S,5R)-5-ethyl-4-(phenylmethyl)-2-morpholinyl]methanol 
• 158554-95-1 (R)-3-Benzyl-4-ethyl-1,1-dioxo-1λ⁶-thiazolidin-2-one 
• 158554-92-8 (R)-3-Benzyl-4-ethyl-thiazolidine-2-thione 
• 194661-95-5 (R)-3-Benzyl-4-ethyl-thiazolidin-2-one 
• 225939-71-9 (R)-N-(1-Allyloxybut-2-yl)-benzylidenamin-N-oxid 
• 225939-67-3 (R)-N-(1-Allyloxybut-2-yl)-benzylamin 
• 888494-16-4 [benzyl-(1-hydroxymethyl-propyl)-amino]-acetic acid tert-butyl ester 
• 888494-25-5 [benzyl-(2-chloro-butyl)-amino]-acetic acid tert-butyl ester 

Relevant academic research and scientific papers

Stereoselective synthesis of 1,4,2-oxazaphosphorines as precursors of chiral α-aminophosphonic acids by intramolecular heterocyclization of β-aldiminoalkylphosphites

The intramolecular version of nucleophilic addison of phosphites to imines was carried out for the first time taking as an example β-aldimino-alkylphosphites, formed from chlorophosphites and β-aldiminoalcohols [N-(benzylidene)-2-aminoethanol and R-(+)-N-(benzylidene)-2-aminobutanol-1]. In these reactions, stereoisomeric 1,4,2-oxazaphospho-rines were obtained in good yields. R-(+)-N-(benzylidene)-2-aminobutanol-1 being used as a precursor, nucleophilic attack by P(III) atone on electrophilic C atom of the C=N group proceeds stereospecifically with participation of only re-face of the two possible diastereotopic faces of the imine double bond to give the epimeric at phosphorus (3R, 5R)-2-(β-chloroethyl)-2-oxo-3-phenyl-5-ethyl-1,4,2-oxazaphosphorines as precursors of nonracemic α-aminophosphonic acids.

Manganese catalyzed reductive amination of aldehydes using hydrogen as a reductant

A one-pot two-step procedure was developed for the alkylation of amines via reductive amination of aldehydes using molecular dihydrogen as a reductant in the presence of a manganese pyridinyl-phosphine complex as a pre-catalyst. After the initial condensation step, the reduction of imines formed in situ is performed under mild conditions (50-100 °C) with 2 mol% of catalyst and 5 mol% of tBuOK under 50 bar of hydrogen. Excellent yields (>90%) were obtained for a large combination of aldehydes and amines (40 examples), including aliphatic aldehydes and amino-alcohols.

Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors

Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

Pyridine containing chiral macrocycles: Synthesis and their enantiomeric recognition for amino acid derivatives

Four novel C2-symmetric enantiomerically pure, chiral pyridine-18-crown-6 type macrocycles containing lipophilic chains at the stereogenic centers were prepared. The enantioselectivity of the new ligands toward the enantiomers of d-,l-amino acid methyl ester derivatives were also determined by 1H NMR titration method. These novel macrocycles have been showed to be strong complexing agents for d- and l-amino acid methyl ester hydrochloride salts (with Kass up to 13590 M-1 and G 0 up to 23.3 kJ mol-1 and selectivity ratio: 80:20) by 1H NMR titration methods. These macrocyclic hosts exhibited enantioselective binding towards the d-enantiomer of valine methyl ester hydrochloride with Kd/Kl up to 5.08 in CDCl3 with 0.25% CD3OD.

Stereocontrolled synthesis of 3-substituted azetidinic amino acids

A set of enantiomerically pure N-disubstituted β-amino alcohols was chlorinated by treatment with thionyl chloride. This reaction gave a mixture of regioisomeric chlorides that could be equilibrated to the more stable regioisomer by heating in DMF. The chlorides thus obtained were engaged in an intramolecular anionic ring-closure and gave access to fully protected enantio- and diastereomerically pure 2,3-cis-disubstituted azetidinic amino acids. One of the latter was deprotected and included in a short peptide sequence. Georg Thieme Verlag Stuttgart.

Reactions of 1,2-imino alcohols with phosphoromonochloridites: Formation of 2-iminoalkyl(phenyl) phosphites

1,2-Imino alcohols existing in a tautomeric equilibrium with the corresponding 1,3-oxazolidines react with phosphoromonochloridites in ether in the presence of triethylamine to form 2-iminoalkyl(phenyl) phosphites as the only reaction products.

Preparation of chiral heterocyclic esters of β-amino acids

Chiral β-amino alcohols were successively prone to N-benzylation, O-allylation and oxidation of the resulting benzylamino group to give nitrones 3 which on hydrolysis afforded chiral hydroxylamines HO-NH-CH(R)-CH2-O-CH2-CH=CH2 ((S)-4: R = Me, Bn, iPr, (R)-4: R = Et). Swern oxidation of methyl 2,2-dimethyl-3-hydroxypropionate (16) and treatment of the resulting aldehyde 17 with hydroxylamines (S)-4b (R = Bn) or (R)-4d (R = Et) provided nitrones 18 that underwent an intramolecular 1,3-dipolar cycloaddition on heating yielding the bicyclic β-amino-acid esters 19b and ent-19d, respectively. Reductive cleavage of the N,O-bond of compounds 19 afforded the eight-membered ring compounds 20b and ent-20d, respectively. N-Benzylalaninol (22) was treated with β-bromo-methacrylate to give the amino alcohol 23. Swern oxidation and subsequent treatment with N-tert-butylhydroxylamine provided the bicyclic ester 26a (R = t-Bu) via the corresponding nitrone 24. Oxime 25 was prepared in an analogous way as 24 with unsubstituted hydroxylamine. It underwent an intramolecular 1.3-dipolar cycloaddition yielding 26b on heating in toluene. Reduction of 26a afforded the pyrrolidine-carboxylic ester 27a.

Synthesis and pyrolytic behaviour of thiazolidin-2-one 1,1-dioxides

Four examples of the chiral thiazolidin-2-one 1,1-dioxides 5 have been prepared by reaction of the appropriate amino alcohols 11 with CS2 in aqueous sodium hydroxide to give the thiazolidine-2-thiones 12, followed by oxidation with KMnO4 under phase-transfer conditions in the presence of benzoic acid, either directly or via the thiazolidin-2-ones 13. Upon flash vacuum pyrolysis (FVP) at 650°C, 5a-c decompose mainly by loss of SO2 to give an alkene and benzyl isocyanate together with other products from fragmentation of the N-benzyl group. A significant minor pathway involves net loss of CO2 and water to give the 2-phenyl-4,5-dihydrothiazoles 21 together with their aromatisation products 22 and 23. A mechanism for this new heterocyclic transformation is proposed involving initial expansion to a cyclic carbamic-sulnnic anhydride (2,1,4-oxathiazin-3-one 1-oxide). The fully assigned 13C NMR spectra are presented for 5, 12 and 13 and the 33S NMR spectrum has been obtained for 5c.