170115-98-7

Usage

Uses

Used in Pharmaceutical Industry:
(R,R)-(-)-Pseudoephedrine Glycinamide is used as a building block for the synthesis of macrocyclic trypanosomal cysteine protease inhibitors. These inhibitors are essential in the development of treatments for trypanosomal diseases, such as African sleeping sickness, by targeting and inhibiting the activity of specific proteases in the parasite.
Additionally, (R,R)-(-)-Pseudoephedrine Glycinamide is used as a building block in the synthesis of α-amino acids. These amino acids are vital components in the development of various pharmaceutical compounds, including those with potential applications in the treatment of neurological disorders, cancer, and other diseases. The unique structural properties of (R,R)-(-)-Pseudoephedrine Glycinamide make it a valuable asset in the design and synthesis of novel therapeutic agents.

Upstream product

• 4530-20-5 BOC-glycine 
• 321-97-1 (1R,2R)-pseudoephedrine 
• 616-34-2 methoxycarbonylmethylamine 
• 170115-96-5 2-amino-N-[(1S,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N-methylacetamide 
• 3282-30-2 pivaloyl chloride 
• 5680-79-5 glycine ethyl ester hydrochloride 

Downstream Products

• 176754-77-1 Carbonic acid 5-{(S)-2-amino-2-[((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-carbamoyl]-ethyl}-4-(tert-butoxycarbonylamino-methyl)-2-methyl-pyridin-3-yl ester tert-butyl ester 
• 225938-47-6 <1R(S),2R>-N-(2-hydroxy-1-methyl-2-phenethyl)-2-amino-N-methyl-4-pentenamide 
• 652990-46-0 (2S)-2-amino-N-[(1R,2R)-2-hydroxy-1-methyl-2-phenylethyl]-N-methyl-4-methylpent-4-enamide 
• 634585-80-1 (S)-2-Amino-11-methoxy-undecanoic acid ((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide 
• 872607-58-4 (S)-2-Amino-6-trimethylsilanyl-hex-4-ynoic acid ((1R,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-methyl-amide 

Relevant academic research and scientific papers

NUCLEIC ACID BINDING COMPOUNDS, METHODS OF MAKING, AND USE THEREOF

The present invention relates to oligomer compounds, including dimers and trimers, formed by a disulfide, sulfinyl thio, olefin or hydrocarbon bond, or a hydrazone exchange bond between two or more monomers. Methods of making the monomers and the oligomers is also disclosed. Use of the compounds for inhibiting the activity of target RNA molecules, particularly those having a secondary structure that include a stem or stem-loop formation. Dimer compounds capable of inhibiting the activity of an HIV-1 RNA frameshifting stem-loop and a (CUG)n expanded repeat stem- loop are disclosed, as are methods of treating diseases associated with these target RNA molecules.

SULFONAMIDE COMPOUNDS

Certain sulfonamide compounds are dual CCK1/CCK2 inhibitors useful in the treatment of CCK1/CCK2 mediated diseases.

Enantioselective Synthesis of Non-Natural Aromatic α-Amino Acids

We present two complementary methods for the stereoselective synthesis of non-natural α-amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R- or S-configured enantiopure amino acids with either C2 or C3 linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium-catalyzed Suzuki cross-coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final "racemization-proof" procedures. The protecting groups chosen for the α-amino acids should be compatible with solid-phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.

Aspartyl protease inhibitors

The present invention provides compounds having the formula: wherein R1, R′, R2, R3, R3′, R4, X1, X2 and X3 are as defined herein, and pharmaceutical compositions thereof. The present invention also provides methods of inhibiting proteases, more specifically aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimer's Disease). The present invention also provides methods for preparing compounds of the invention.

The Synthesis of Two Furan-Based Analogues of the α′,β ′-Epoxy Ketone Proteasome Inhibitor Eponemycin

Myers's methodology for enantioselective amino acid synthesis was employed to prepare the N-Boc didehydroleucine amide derivative 15 and to effect its conversion into the acylfuran intermediate 17. Coupling of 19 (R = H) with N-(isooctanoyl)serine provided the furan-based analogue 4 of eponemycin (de = 96 %), a peptide epoxide with potent cytotoxic and anti-angiogenesis properties. In an identical fashion the corresponding unsaturated analogue 5 of eponemycin was prepared (de = 48%). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

ASPARTYL PROTEASE INHIBITORS

The present invention provides compounds having formula (I): wherein R’, R0, R1, X1, R2, R3, R3’, X2, X3, and R4 are as defined herein, and pharmaceuticals compositions thereof. The present invention also provides methods of inhibiting proteases, more specially aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimer’s Disease). The present invention also provides methods for preparing compounds of the invention.

Greatly simplified procedures for the synthesis of α-amino acids by the direct alkylation of pseudoephedrine glycinamide hydrate

A modified procedure for the synthesis of highly enantiomerically enriched α-amino acids is described that involves the direct alkylation of pseudoephedrine glycinamide hydrate (1 · H2O) followed by hydrolysis. The modified procedure was developed to overcome several inconvenient aspects of our earlier reported procedure. Advantages of the new method include (1) a greatly simplified one-step synthesis of the alkylation substrate (1 · H2O) by the direct combination of glycine methyl ester hydrochloride with pseudoephedrine in the presence of lithium tert-butoxide, (2) the use of the weaker base lithium hexamethyldisilazide (LHMDS) in lieu of lithium diisopropylamide (LDA) for the enolization reaction, (3) a protocol for the direct alkylation of 1 · H2O without the need for prior drying of the alkylation substrate, and (4) a one-step alkylation procedure that generates LHMDS and anhydrous lithium chloride simultaneously from the reaction of lithium metal with n-hexyl chloride in the presence of hexamethyldisilazane.

Highly practical methodology for the synthesis of D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids

Full details are provided for an exceedingly practical method to synthesize D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids, employing as a key step the asymmetric alkylation of pseudoephedrine glycinamide (1) or pseudoephedrine sarcosinamide (2). Practical procedures for the synthesis of 1 and 2 from pseudoephedrine and glycine methyl ester or sarcosine methyl ester, respectively, are presented. Optimum protocols for the enolization and subsequent alkylation of 1 and 2 are described. Alkylation reactions of 1 and 2 are found to be quite efficient with a wide range of alkyl halide substrates, and the products are formed with high diastereoselectivity. The products of these alkylation reactions are hydrolyzed efficiently and with little to no racemization simply by heating in water or water-dioxane mixtures. This protocol provides an exceedingly practical method for the preparation of salt-free α-amino acids of high enantiomeric purity. Alternatively, the alkylation products may be hydrolyzed in high yield and with little to no racemization by heating with aqueous sodium hydroxide. The alkaline hydrolyzate can then be treated with an acylating reagent to provide directly highly enantiomerically enriched N-protected derivatives such as N-Boc and N-Fmoc. Key features necessary for the successful execution of these experimental procedures are identified.

A One-Step Synthesis of Pseudoephedrine Glycinamide, a Versatile Precursor for the Synthesis of a α-Amino Acids

Both enantiomers of pseudoephedrine glycinamide were synthesized by either of two procedures: (1) a standard two-step coupling of N-Boc-Gly with pseudoephedrine followed by deprotection, or (2) a more economical one-step coupling reaction of Gly-OMe with pseudoephedrine mediated by LiCl and base.