167498-32-0Relevant academic research and scientific papers
An expedient route for the reduction of carboxylic acids to alcohols employing 1-propanephosphonic acid cyclic anhydride as acid activator
Nagendra,Madhu,Vishwanatha,Sureshbabu, Vommina V.
experimental part, p. 5059 - 5063 (2012/09/22)
A simple and efficient method for the synthesis of alcohols from the corresponding carboxylic acids is described. Activation of carboxylic acid with 1-propane phosphonic acid cyclic anhydride (T3P) and subsequent reduction of the intermediate phosphonic anhydride with NaBH4 yield the alcohol in excellent yields with good purity in less duration. Reduction of several alkyl/aryl carboxylic acids and Nα-protected amino acids/peptide acids as well as Nβ-protected amino acids was successfully carried out to obtain corresponding alcohols in good yields and the products characterized. The procedure is mild, safe, simple and the isolation of the products is easy.
Simple and efficient synthesis of Fmoc/Boc/Cbz-protected-β-amino alcohols and peptidyl alcohols employing Boc2O
Lalithamba,Sureshbabu, Vommina V.
experimental part, p. 1372 - 1378 (2011/01/13)
An efficient method for the activation of Fmoc/Boc/Cbz-protected amino acids using Boc2O and the reduction of the in situ generated carbonic-carbonic anhydride to their corresponding 1β-amino alcohols using sodium borohydride has been described. The method is simple, rapid and free from racemization. Besides, the protocol is also extended for the conversion of N-urethane protected peptide acids to their corresponding alcohols. Copyright
Simple and rapid synthesis of Nα-urethane protected β-amino alcohols and peptide alcohols employing HATU
Surcshbabu, Vommina V.,Sudarshan,Chennakrishnareddy
experimental part, p. 574 - 579 (2009/12/06)
The activation of the Nα--urcihanc protected (Fmoc-/Boc-/Z-/Bsmoc) α-amino acids employing l-[bis(dimethylamino)- methylene]-lH-l,2,3-triazolo-[4,5-6]pyridinium.0hexa-flurophosphate-3-oxide (HATU) followed by reduction of the in situ generated -OAt ester with NaBH 4 results in the corresponding ss-amino alcohols in good yields. This synthesis is the first demonstration of the application of the efficient coupling agent HATU for practical synthesis of ss-amino alcohols. The protocol is general for all common N-protecting groups including the highly base sensitive Bsmoc group. The protocol has also been successfully extended for the synthesis of peptide alcohols.
Structure-based design, synthesis and evaluation of conformationally constrained cysteine protease inhibitors
Scheidt, Karl A.,Roush, William R.,McKerrow, James H.,Selzer, Paul M.,Hansell, Elizabeth,Rosenthal, Philip J.
, p. 2477 - 2494 (2007/10/03)
The inhibition of cysteine proteases is being studied as a strategy to combat parasitic diseases such as Chagas' disease, leishmaniasis, and malaria. Cruzain is the major cysteine protease of Trypanosoma cruzi, the etiologic agent of Chagas' disease. A crystal structure of cruzain, covalently inactivated by fluoromethyl ketone inhibitor 1 (Cbz-Phe-Ala-FMK), was used as a template to design potential inhibitors. Conformationally constrained γ-lactams containing electrophilic aldehyde (12, 17, 18, 25, 26, and 29) or vinyl sulfone (43, 44, and 46) units were synthesized. Constrained lactam 26 had IC50 values of ca. 20nM against the Leishmania major protease and ca. 50nM versus falcipain, an important cysteine protease isolated from Plasmodium falciparum. However, all of the conformationally constrained inhibitors were weak inhibitors of cruzain, compared to unconstrained peptide aldehyde (e.g. 5 ) and vinyl sulfone inhibitors (e.g. 48, which proved to be an excellent inhibitor of cruzain with an apparent second order inhibition rate constant (k(inact)/K(i)) of 634,000s-1M-1). A significant reduction in activity was also observed with acyclic inhibitors 30 and 51 containing α-methyl phenylalanine residues at the P2 position. These data indicate that the pyrrolidinone ring, especially the quarternary center at P2, interferes with the normal substrate binding mode with cruzain, but not with falcipain or the leishmania protease. Copyright (C) 1998 Elsevier Science Ltd.
Synthesis and stereoselective C-C bond-forming reactions of peptide aldehydes
Reetz, Manfred T.,Griebenow, Nils
, p. 335 - 348 (2007/10/03)
The reaction of the activated form of N-protected amino acids 6 and 10 or peptides 14 and 18 with chiral amino alcohols derived from the corresponding α-amino acids affords peptide alcohols which can be oxidized under Swern conditions to produce the corresponding peptide aldehydes 9, 12, 16 and 20. The rational synthesis of diastereomeric di- and tripeptide aldehydes, e.g., (S,S)- or (R,S)-dipeptides as well as (S,S,S)- or (R,S,S)-tripeptides is possible by proper choice of the respective building blocks [(S)- versus (R)-amino acids]. The compounds can be prepared without any undesired α-epimerization. However, the long-term configurational stability depends upon the configuration at the remote stereogenic center, e.g., (R,S)-dipeptide aldehydes epimerize faster than the (S,S) diastereomers. Di- and tripeptide aldehydes 9, 12, 16 and 20 undergo chelation-controlled Grignardtype additions with Me2CuLi that involve little or no undesired α-epimerization. The (S,S)- and (R,S)-dipeptide aldehydes 9 and 12 undergo chelation-controlled pinacol reactions induced by the low-valent vanadium reagent [V2Cl3(THF)6]2[Zn2Cl 6]. The major products in both cases are the corresponding C2-symmetric diols 33 and 36, respectively, which are of interest as potential HIV-protease inhibitors. The degree of stereoselectivity is significantly higher in the case of the (S,S)-dipeptide aldehydes relative to the (R,S) analogs, an observation which can be explained on the basis of three-point binding of the peptides to vanadium. VCH Verlagsgesellschaft mbH, 1996.
