210428-06-1

Upstream product

• 210428-05-0 (S)-methyl 2-(tert-butoxycarbonylamino)-3-(4-(tert-butyldiphenylsilyloxy)phenyl)propanoate 
• 1262483-06-6 C₃₂H₄₂N₂O₅Si 
• 151133-14-1 Boc-Tyr-Weinreb amide 
• 3978-80-1 Boc-Tyr-OH 
• 60-18-4 L-tyrosine 
• 3417-91-2 L-tyrosine methyl ester HCl 
• 4326-36-7 (S)-N-(tert-butoxycarbonyl)tyrosine methyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 210428-07-2 (E)-(S)-3-tert-Butoxycarbonylamino-4-[4-(tert-butyl-diphenyl-silanyloxy)-phenyl]-but-1-ene-1-sulfonic acid methyl ester 
• 210428-66-3 {(E)-(S)-3-((E)-(S)-3-tert-Butoxycarbonylamino-4-methyl-pent-1-ene-1-sulfonylamino)-4-[4-(tert-butyl-diphenyl-silanyloxy)-phenyl]-but-1-ene-1-sulfonylamino}-acetic acid methyl ester 
• 210428-55-0 [(E)-(S)-1-[4-(tert-Butyl-diphenyl-silanyloxy)-benzyl]-3-((E)-(S)-1-methyl-3-sulfamoyl-allylsulfamoyl)-allyl]-carbamic acid tert-butyl ester 
• 210428-62-9 {(E)-(S)-3-tert-Butoxycarbonylamino-4-[4-(tert-butyl-diphenyl-silanyloxy)-phenyl]-but-1-ene-1-sulfonylamino}-acetic acid methyl ester 
• 210428-10-7 {(E)-(S)-1-[4-(tert-Butyl-diphenyl-silanyloxy)-benzyl]-3-chlorosulfonyl-allyl}-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Universal peptidomimetics

This paper concerns peptidomimetic scaffolds that can present side chains in conformations resembling those of amino acids in secondary structures without incurring excessive entropic or enthalpic penalties. Compounds of this type are referred to here as minimalist mimics. The core hypothesis of this paper is that small sets of such scaffolds can be designed to analogue local pairs of amino acids (including noncontiguous ones) in any secondary structure; i.e., they are universal peptidomimetics. To illustrate this concept, we designed a set of four peptidomimetic scaffolds. Libraries based on them were made bearing side chains corresponding to many of the protein-derived amino acids. Modeling experiments were performed to give an indication of kinetic and thermodynamic accessibilities of conformations that can mimic secondary structures. Together, peptidomimetics based on these four scaffolds can adopt conformations that resemble almost any combination of local amino acid side chains in any secondary structure. Universal peptidomimetics of this kind are likely to be most useful in the design of libraries for high-throughput screening against diverse targets. Consequently, data arising from submission of these molecules to the NIH Molecular Libraries Small Molecule Repository (MLSMR) are outlined.

Synthesis of chiral vinylogous sulfonamidopeptides (vs-peptides)

Chiral vinylogous amino sulfonic acids (vs-amino acids) were synthesized starting from either L- or D-α-amino acids via N-Boc-α-amino aldehydes. Wittig-Horner reaction with methyl (or ethyl) diethylphosphoryl methanesulfonate and nBuLi gave the corresponding α,β-unsaturated sulfonates in high yield and complete (E) stereoselectivity. Cleavage of the methyl (ethyl) ester was effected by treatment of the sulfonates with nBu4NI in refluxing acetone. Treatment of the nBu4N+ sulfonate salts with SO2Cl2/PPh3/CH2Cl2 gave the corresponding sulfonyl chlorides as stable chromatographable compounds. The synthetic sequence proved successful not only starting from α-amino acids carrying unfunctionalized side-chains (Ala, Val, Phe, Leu, Pro), but also with functionalized α-amino acids (Ser, Tyr, Gln) provided that the side chains were suitably protected. The sulfonyl chlorides were coupled with the amine salts to give vs-dipeptides. Amine hydrochlorides were prepared from N-Boc derivatives by treatment with HCl in methanol or ethyl acetate. The process was further iterated to give vstripeptides and vs-tetrapeptides. The above procedure was also used to synthesize "mixed" peptides, which incorporate both proteinogenic α-amino acids and vs-amino acids. Proteinogenic α-amino acids were incorporated at both the C-terminal and the N-terminal position.