134899-86-8

Upstream product

• 117176-06-4 (S)-4-Methyl-4,5-dihydro-oxazole-4-carboxylic acid methyl ester 
• 67-56-1 methanol 
• 3398-40-1 (S)-(+)-2-amino-2-methyl-3-hydroxypropanoic acid 
• 5424-29-3 2-amino-3-hydroxy-2-methyl-propionic acid 

Downstream Products

• 191725-34-5 N-benzoyl-α-methylserine methyl ester 

Relevant academic research and scientific papers

Control of chemoselectivity in Dieckmann ring closures leading to tetramic acids

An efficient strategy for the control of the chemoselectivity in Dieckmann ring closures leading to tetramic acids derived from serine and α-methyl serine is reported, and this provides pathways to diversely substituted systems from a common starting material.

Design and synthesis of peptide-based macrocyclic cyclophilin inhibitors

The efficient assembly of an 18-membered macrocyclic peptide core was realized by a straightforward and convergent approach utilizing ring-closing metathesis of the corresponding linear tetrapeptides as the key transformation. This approach allowed for the facile preparation of a focused library of novel macrocycles that culminated in the discovery of a cyclophilin A inhibitor with a Kd= 5.4 μM.

An efficient enantioselective synthesis of (S)-α-methyl-serine methyl ester hydrochloride via asymmetrically catalyzed amination

We present the synthesis of enantiomerically pure (S)-α-methyl-serine methyl ester hydrochloride from 2-methyl-3-((4-(trifluoromethyl)benzyl)oxy)propanal and di-p-chlorobenzyl azodicarboxylate via asymmetrically catalyzed amination with naphthylalanine de

Total Synthesis of Tambromycin by Combining Chemocatalytic and Biocatalytic C?H Functionalization

A combination of genomic and metabolomic approaches recently resulted in the identification of a nonribosomal tetrapeptide tambromycin, which possesses promising antiproliferative activity and several unusual structural features, including a densely substituted indole, a methyloxazoline ring, and an unusual pyrrolidine-containing amino acid called tambroline. In this work, we identify a concise synthetic route to access tambromycin, which relies on the strategic use of biocatalytic and chemocatalytic C?H functionalization methods to prepare two key precursors to the natural product in an efficient and scalable manner. The success of our study highlights the benefits of applying the principles of biocatalytic retrosynthesis as well as C?H functionalization logic to the synthesis of complex molecular scaffolds.

Total Synthesis of Mycobacterium tuberculosis Dideoxymycobactin-838 and Stereoisomers: Diverse CD1a-Restricted T Cells Display a Common Hierarchy of Lipopeptide Recognition

Mycobacterium tuberculosis produces dideoxymycobactin-838 (DDM-838), a lipopeptide that potently activates T cells upon binding to the MHC-like antigen-presenting molecule CD1a. M. tuberculosis produces DDM-838 in only trace amounts and a previous solid-phase synthesis provided sub-milligram quantities. We describe a high-yielding solution-phase synthesis of DDM-838 that features a Mitsunobu substitution that avoids yield-limiting epimerization at lysine during esterification, and amidation conditions that prevent double-bond isomerization of the Z-C20:1 acyl chain, and provides material with equivalent antigenicity to natural DDM-838. Isomers of DDM-838 that varied in stereochemistry at the central lysine and the C20:1 acyl chain were compared for their ability to be recognised by CD1a-restricted T cell receptors (TCRs). These TCRs, derived from unrelated human donors, exhibited a similar spectrum of reactivity towards the panel of DDM-838 isomers, highlighting the exquisite sensitivity of lipopeptide-reactive T cells for the natural DDM stereochemistry.

Complementary syntheses of N,O-protected-(S)-2-methylserine on a multikilogram scale

Two complementary and scalable approaches have been used to manufacture multikilogram quantities of N,O-protected-(S)-2-methylserine. The first approach uses a diastereomeric salt resolution of 2-methylserine methyl ester as the (1S)-(+)-camphorsulfonate salt, and was used to rapidly access 15 kg of (S)-3-tert-butoxycarbonyl-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid with >99% ee. The second approach involves a stereoselective enolate methylation of a chiral cyclic l-serine derivative under cryogenic conditions. The four-step telescoped process, starting from l-serine methyl ester, was used to manufacture 20 kg of (2R,4S)-2-tert-butyl-3-tert-butoxycarbonyl-4-methyl-1,3- oxazolidine-4-carboxylic acid in 52% overall yield and 98% ee. The advantages and disadvantages for scale-up of both approaches are discussed.

MASKED CARBOXYLATE NEOPENTYL SULFONYL ESTER CYCLIZATION RELEASE PRODRUGS OF ACAMPROSATE, COMPOSITIONS THEREOF, AND METHODS OF USE

Masked carboxylate neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs

MONOCYCLIC CGRP RECEPTOR ANTAGONISTS

The present invention is directed to compounds of the formula (I) : (wherein variables A1, A2, A3, A4, A5, A6, A7, A8, G1, G2, G3, G4, J, Q, Ea, Eb, Ec, R6, R7, RPG and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Catalytic enantioselective electrophilic aminations of acyclic α-alkyl β-carbonyl nucleophiles

Highly enantioselective aminations of acyclic α-alkyl β-keto thioesters and trifluoroethyl α-methyl α-cyanoacetate (12) with as low as 0.05 mol% of a bifunctional cinchona alkaloid catalyst were established. This ability to afford high enantioselectivity

Synthesis and biological evaluation of two chemically modified peptide epitopes for the class i MHC protein HLA-B*2705

The T-cell receptor of a CD8+ T-cell recognises peptide epitopes bound by class I major histocompatibility complex (MHC) glycoproteins presented in a groove on their upper surface. Within the groove of the MHC molecule are 6 pockets, two of whi