218800-60-3Relevant academic research and scientific papers
Preparation of the β2-homoselenocysteine derivatives Fmoc-(S)-β2hSec(PMB)-OH and Boc-(S)-β2hSec(PMB)- OH for solution and solid-phase peptide synthesis
Patora-Komisarska, Krystyna,Jadwiga Podwysocka, Dominika,Seebach, Dieter
, p. 1 - 17 (2011/03/17)
Fmoc-β2hSer(tBu)-OH was converted to Fmoc-β2hSec(PMB)-OH in five steps. To avoid elimination of HSeR, the selenyl group was introduced in the second last step (Fmoc- β2hSer(Ts)-OAll→Fmoc-β2hSec(PMB)-OAll). In a similar way, the N-Boc-protected compound was prepared. With the β2hSe-derivatives, 21 β2-amino-acid building blocks with proteinogenic side chains are now available for peptide synthesis. Copyright
Preparation of protected β2- and β3- homocysteine, β2- and β3-homohistidine, and β2-homoserine for solid-phase syntheses
Lelais, Gerald,Micuch, Peter,Josien-Lefebvre, Delphine,Rossi, Francesco,Seebach, Dieter
, p. 3131 - 3159 (2007/10/03)
The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of β-peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two β3-homoamino acid derivatives were obtained by Arndt-Eistert methodology from Boc-His(Ts)-OH and Fmoc-Cys(PMB)-OH (Schemes 2-4), with the side-chain functional groups' reactivities requiring special precautions. The β2-homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti-enolates to formaldehyde (generated in situ from trioxane) and subsequent functional-group manipulations. These include OH → OtBu etherification (for β2hSer; Schemes 5 and 6), OH → STrt replacement (for β2hCys; Scheme 7), and CH 2OH → CH2N3 → CH2NH 2 transformations (for β2hHis; Schemes 9-11). Including protection/deprotection/re-protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (tR), melting points, optical rotations, HPLC on chiral columns, IR, 1H- and 13C-NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X-ray crystal-structure analysis.
Enantioselective preparation of 2-aminomethyl carboxylic acid derivatives: Solving the β2-amino acid problem with the chiral auxiliary 4-isopropyl-5,5-diphenyloxazolidin-2-one (DIOZ)
Seebach, Dieter,Schaeffer, Laurent,Gessier, Francois,Bindschaedler, Pascal,Jaeger, Corinna,Josien, Delphine,Kopp, Sascha,Lelais, Gerald,Mahajan, Yogesh R.,Micuch, Peter,Sebesta, Radovan,Schweizer, Bernd W.
, p. 1852 - 1861 (2007/10/03)
Multigram amounts of suitably protected β2-amino acids with 17 of the 20 proteinogenic side chains are prepared by diastereoselective reactions of Li, B, or Ti enolates of the corresponding 3-acyl-4-isopropyl-5,5-diphenyloxazolidin-2-ones (acyl-DIOZ; 1) with appropriate electrophiles (amidomethylation, hydroxyalkylation, (benzyloxycarbonyl)methylation) in yields of 55-90% and with diastereoselectivities of 80 to > 97% (Scheme). The primary products 2-8 thus obtained are converted to protected β2-amino acids by standard procedures (Table 1). Many of the DIOZ derivatives are highly crystalline compounds (31 X-ray crystal structures in Table 2). The chiral auxiliary DIOZ, readily prepared in either enantiomeric form, is recovered with high yield.
A useful modification of the Evans auxiliary: 4-Isopropyl-5,5- diphenyloxazolidin-2-one
Hintermann, Tobias,Seebach, Dieter
, p. 2093 - 2126 (2007/10/03)
The 4-isopropyl-5,5-diphenyloxazolidinone (1) is readily prepared from (R)- or (S)-valine ester, PhMgBr, and ethyl chlorocarbonate. It has a melting point of ca. 250°, a low solubility in most organic solvents, and a C=O group which is sterically protected from nucleophilic attack. Thus, the soluble N-acyl-oxazolidinones (7-16) can be prepared from 1 with BuLi at temperatures around 0°instead of - 78°(Scheme 3), their Li enolates can be generated with BuLi, rather than with LDA, and deacylation in the final step of the procedure can be achieved with NaOH at ambient temperatures (Scheme 12), with facile recovery of the precipitating auxiliary 1 (filtering, washing, and drying). The following reactions of N-acyl-oxazolidinones from 1 have been investigated: alkylations (Scheme 4), aminomethylations and hydroxymethylations (Scheme 5), aldol additions (Schemes 6 and 7), Michael additions (Schemes 9 and 10), and a (4 + 2) cycloaddition (Scheme 11). The well-known features of reactions following the Evans methodology (yield, diastereoselectivity, dependence on conditions, counter ions, additives etc.) prevail in these transformations. Most products, however, have higher melting points and a much more pronounced crystallization tendency than those derived from conventional oxazolidinones, and can thus be purified by recrystallization, avoiding chromatography (Table 1). The disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is more than compensated by the ease of its application, especially on large scale. A number of crystal structures of oxazolidinones derived from 1 and a TiCl4 complex of an oxazolidinone are described and discussed in view of the diastereoselective-reaction mechanisms.
