182958-73-2

Upstream product

• 676-58-4 methylmagnesium chloride 
• 182959-29-1 1-oxa-4-azaspiro[4,5]decane-(3S)-3,4-dicarboxylic acid 4-tert-butyl ester 3-methyl ester 
• 182957-71-7 (S)-4-(1-hydroxy-1-methylethyl)-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 
• 2766-43-0 N-tert-butyloxycarbonyl-L-serine methyl ester 
• 95715-86-9 (S)-2,2-dimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 4-methyl ester 
• 75-16-1 methylmagnesium bromide 
• 95715-85-8 2-(tert-butoxycarbonylamino)-3-hydroxypropionic acid methyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 182958-67-4 (3S)-3-(1-hydroxy-1-methylethyl)-1-oxa-4-azaspiro[4.5]decane-4-carboxylic acid tert-butyl ester 

Downstream Products

• 288159-40-0 (R)-2-((tert-butoxycarbonyl)amino)-3-hydroxy-3-methylbutanoic acid 
• 102507-13-1 N-(tert-butoxycarbonyl)-3-hydroxy-L-valine 

Relevant academic research and scientific papers

Organic total synthesis method of D-penicillamine

The invention discloses an organic total synthesis method of D-penicillamine, which comprises the following steps: carrying out Grignard reaction on a derivative of Lserine ester and a methyl Grignardreagent to obtain a first intermediate; carrying out oxidation reaction on the first intermediate and an oxidizing agent to obtain a second intermediate; carrying out sulfonylation reaction on the second intermediate and a sulfonylation reagent to obtain a third intermediate; carrying out thiolation reaction on the third intermediate and a vulcanization reagent to obtain a fourth intermediate; and carrying out hydrolysis reaction on the fourth intermediate to obtain the D-penicillamine. The initial raw materials are cheap and easy to obtain, particularly, cheap, easy-to-obtain and high-optical-purity Lserine ester derivatives can be used as the raw materials, the whole synthetic route for preparing the Dapenem is a new organic total synthesis process route, the process is simple, the reaction condition requirement is low, no toxin is left, and the safety performance is good; the product yield and the optical purity are high; and large-scale production is easy to realize.

NIPECOTIC ACID DERIVATIVE AND USE THEREOF FOR MEDICAL PURPOSES

The present invention aims to provide a compound having an sEH-inhibiting activity and to provide a pharmaceutical having a therapeutic effect and a prophylactic effect on chronic renal disease and pulmonary hypertension based on the sEH-inhibiting action. The present invention provides nipecotic acid derivatives represented by the chemical formula below and pharmaceutically acceptable salts thereof.

Total synthesis of the large non-ribosomal peptide polytheonamide B

Polytheonamide B is by far the largest non-ribosomal peptide known at present, and displays extraordinary cytotoxicity (EC50 =68 pg ml -1 , mouse leukaemia P388 cells). Its 48 amino-acid residues include a variety of non-proteinogenic d- and l-amino acids, and the absolute stereochemistry of these amino acids alternate in sequence. These structural features induce the formation of a stable β-strand-type structure, giving rise to an overall tubular structure over 30A? in length. In a biological setting, this fold is believed to transport cations across the lipid bilayer through a pore, thereby acting as an ion channel. Here, we report the first chemical construction of polytheonamide B. Our synthesis relies on the combination of four key stages: syntheses of non-proteinogenic amino acids, a solid-phase assembly of four fragments of polytheonamide B, silver-mediated connection of the fragments and, finally, global deprotection. The synthetic material now available will allow studies of the relationships between its conformational properties, channel functions and cytotoxicity.

Serine as chiral educt for the practical synthesis of enantiopure N-protected β-hydroxyvaline

N-tert-Butyloxycarbonyl- and N-benzenesulfonyl-β-hydroxyvalines 1a and 1b were, respectively, synthesized in enantiomerically pure form by a two-step protocol from their enantiomeric N-protected serine methyl esters 2a and 2b. The addition of CH3MgBr to 2a and 2b provided diols 3a and 3b, respectively as major products in 83% and 81% yields. Selective oxidation of diols 3a and 3b was performed using a TEMPO, NaClO2, NaOCl cocktail in 96% and 93% respective yields. This two-step process effectively furnished multigram amounts of enantiopure N-Boc-β-hydroxyvaline 1a.

Facile synthesis of L-3,4-didehydrovaline constituting an antibiotic, phomopsin A

A convenient synthesis of δ,γ-unsaturated valine (L-3,4- didehydrovaline), an important constituent of an antibiotic phomopsin A, was achieved from H-D-Ser-OH through a seven-step conversion in 31percent overall yield.

Grignard reactions to chiral oxazolidine aldehydes

Modest to high levels of asymmetric induction are observed with Grignard additions to Garner type aldehydes. The resultant secondary alcohols are important precursors of chiral building blocks for asymmetric synthesis and we have demonstrated that they can be readily converted into their respective γ-hydroxy-β-amino alcohols and β-hydroxyamino acids. Additionally, aryloxy ethers, important components of many natural products, can be obtained from these precursors.