136497-27-3

Upstream product

• 15136-29-5 Boc-Phe-Ala-OMe 
• 75-65-0 tert-butyl alcohol 
• 21691-50-9 Ala-OtBu 
• 7535-56-0 N-t-butoxycarbonyl-L-phenylalanine 4-nitrophenyl ester 
• 13404-22-3 tert-butyl L-alaninate hydrochloride 
• 142955-51-9 N-butoxycarbonyl-L-phenylalanine anhydride 
• 51987-73-6 (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid methyl ester 
• 133010-06-7 1,1-dimethylethyl S-N-(1-fluorocarbonyl-2-phenylethyl)carbamate 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 

Relevant academic research and scientific papers

Automated synthesis and purification of amides: Exploitation of automated solid phase extraction in organic synthesis

Automated parallel synthesis of small organic molecules, either as single entities or as mixtures, offers the potential for the rapid optimization of physical and biological properties of a molecule Currently, emphasis has been placed on solid phase synthesis technology to accomplish the rapid preparation of large numbers of molecules. Automated solution phase synthesis is an alternative approach which has the advantages of having shorter development times and being more amenable to scaleup. Utilizing commercially available liquid handlers for reaction setup and exploiting automated solid phase extraction for product purification, a procedure has been developed to prepare and purify up to 100 amide analogs, simultaneously. Both carbodiimide mediated couplings and p-nitro-phenyl ester displacements have been carried out using this procedure. Product amides having overall neutral or basic character have been prepared in good yield and with good to excellent purities.

Rapid and column-free syntheses of acyl fluorides and peptides usingex situgenerated thionyl fluoride

Thionyl fluoride (SOF2) was first isolated in 1896, but there have been less than 10 subsequent reports of its use as a reagent for organic synthesis. This is partly due to a lack of facile, lab-scale methods for its generation. Herein we report a novel protocol for theex situgeneration of SOF2and subsequent demonstration of its ability to access both aliphatic and aromatic acyl fluorides in 55-98% isolated yields under mild conditions and short reaction times. We further demonstrate its aptitude in amino acid couplings, with a one-pot, column-free strategy that affords the corresponding dipeptides in 65-97% isolated yields with minimal to no epimerization. The broad scope allows for a wide range of protecting groups and both natural and unnatural amino acids. Finally, we demonstrated that this new method can be used in sequential liquid phase peptide synthesis (LPPS) to afford tri-, tetra-, penta-, and decapeptides in 14-88% yields without the need for column chromatography. We also demonstrated that this new method is amenable to solid phase peptide synthesis (SPPS), affording di- and pentapeptides in 80-98% yields.

Substrate-directed lewis-acid catalysis for peptide synthesis

A Lewis-acid-catalyzed method for the substrate-directed formation of peptide bonds has been developed, and this powerful approach is utilized for the new "remote" activation of carboxyl groups under solvent-free conditions. The presented method has the following advantages: (1) the high-yielding peptide synthesis uses a tantalum catalyst for any amino acids; (2) the reaction proceeds without any racemization; (3) the new substrate-directed chemical ligation using the titanium catalyst is applicable to convergent peptide synthesis. These advantages overcome some of the unresolved problems in classical peptide synthesis.

Synthesis of highly substituted imidazolidine-2,4-dione (Hydantoin) through Tf2O-mediated dual activation of Boc-protected dipeptidyl compounds

Highly substituted chiral hydantoins were readily synthesized from simple dipeptides in a single step under mild conditions. This reaction proceeded through the dual activation of an amide and a tert-butyloxycarbonyl (Boc) protecting group by Tf2O-pyridine. This method was successfully applied in the preparation of a variety of biologically active compounds, including drug analogs and natural products.

Sodium methoxide: A simple but highly efficient catalyst for the direct amidation of esters

A simple NaOMe catalyst provides superior accessibility to a wide variety of functionalized amides including peptides through direct amination of esters in an atom-economical and environmentally benign way.

Solvent-free synthesis of peptides

Chamical Equation Presentation A crush on sweetness! The coupling of a urethane-protected N-carboxyanhydride of an amino acid with another amino acid derivative under ball-milling conditions gives a protected dipeptide in very high yield (see scheme; PG: protecting group). The reaction takes place in the solid state. The synthesis was applied to the preparation of a tri peptide and the sweetener aspartame, without any organic solvent or purification.

Transesterifications with 1,8-Diazabicycloundec-7-ene/Lithium Bromide (DBU/LiBr) - Also Applicable to Cleavage of Peptides from Resins in Merrifield Syntheses

A mixture of the amidine base 1,8-diazabicycloundec-7-ene (DBU) and LiBr (preferably 0.5 and 5 equiv., resp.) turns out to be a highly efficient catalyst (at 0-25 deg C) for saponifications (in THF/H2O) and transesterifications (in ROH).The scope and limitations of the method are determined using ca. two dozens of different ester/alcohol combinations (Schemes 2 and 3).The investigation is focused on peptides as substrates.Under carefully controlled conditions, no epimerization occurs with N-Boc- and N-Z-protected peptide esters, when methyl, ethyl, isopropyl, or allyl esters are the products, as shown for peptides containing up to six amino acids, with Ala, Leu, MeLeu, Asp(OEt), or Tyr at the C-terminus (Scheme 3 and Tables 1 and 2).Hydrolytic and transesterifying detachments of Boc-Leu-Ala-Gly-Val-OR and Boc-Leu-Ala-Gly-Phe-OR (R = H, Me) from PAM and Wang resins (1-8 h at 0-25 deg C, 2 equiv. of DBU, 5 equiv. of LiBr) can be achieved by this method without epimerization of the C-terminal stereogenic center; a comparison with other methods (HF, Ti(OR)4) is given (Schemes 4 and 5).Possible protecting-group strategies involving the DBU/LiBr method are discussed (Table 3).Extensive experimental details are given.