78605-47-7

Upstream product

• 3082-75-5 L-Alanine ethyl ester 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 64-17-5 ethanol 
• 15136-29-5 Boc-Phe-Ala-OMe 
• 1330059-29-4 N-tert-butoxycarbonyl-L-phenylalanine 9-fluorenylmethyl thioester 
• 1115-59-9 (S)-alanine ethyl ester hydrochloride 
• 81000-39-7 (S)-2-((tert-butoxycarbonyl)amino)-3-phenylpropanethioic S-acid 

Relevant academic research and scientific papers

Processes for forming amide bonds and compositions related thereto

The disclosure relates to methods for producing amide bonds and reagents related thereto. In some embodiments, the disclosure relates to methods of producing an amide comprising mixing an O-silylated thionoester and an amine under conditions such that an amide is formed. In another embodiment, the disclosure relates to mixing a thiolacid, a silylating agent, and an amine under conditions such that an amide is formed.

In situ carboxyl activation using a silatropic switch: A new approach to amide and peptide constructions

The novel reactivity of O-silylthionoesters with amine nucleophiles to generate oxoamides (rather than thioamides) is described. A straightforward first-generation trimethylsilylation protocol using bistrimethylsilylacetamide (BSA) combined with the unique reactivity of the O-silylthionoesters toward 1° and 2° amines to generate oxoamides provides the simplest means of activating a thiol acid for peptide bond formation at neutral pH. Excellent stereoretention is observed.

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.

2-HALOVINYL ARYL SULFONES: NEW COUPLING REAGENTS FOR CARBOXAMIDE FORMATION

E-2-Chlorovinyl p-nitrophenyl sulfone 6 and 2-bromo-2-trifluoromethylvinyl phenyl sulfone 7a reacted with carboxylic acids in the presence of a molar equiv of Et3N affording the corresponding 2-acyloxyvinyl sulfones 8, 11, 17, 18, 22, 25, 28 and 29.The latter, on treatment with amines, gave amides 9, 13, 19, 23 and 26 and peptides 30 and 32.These reagents 6 and 7a were also used for the formation of N-methylanilides 13d, 13e, 19d, 23 and 26.Particularly, 6 was successfully used for synthesis of a macrocyclic lactam 23 involving a N-methylanilide moiety.The amidation reac tions proceeded under essentially neutral conditions.Therefore, base-sensitive β-hydroxycarboxy-N-methylanilides such as 26, whose structural unit was involved in maytansine 5, could be prepared by the present method.The reagent 6 was also effective for the preparation of peptides such as Val-N-MeVal derivatives (e.g.32), which were difficult to prepare by other methods.

A NEW REAGENT FOR ACTIVATING CARBOXYL GROUPS: DIPHENYL 2-OXO-3-OXAZOLINYLPHOSPHONATE

Diphenyl 2-oxo-3-oxazolinylphosphonate serves as a carboxyl-activating reagent to permit a direct preparation of versatile intermediate, 3-acyl-2-oxazolones or a one-step formation of amides from carboxylic acids.