A new, efficient, and readily available reagent, methyl 2-((succinimidooxy)carbonyl)benzoate (MSB), for N-phthaloylation of amino acids and amino acid derivatives is described. The phthaloylation procedure is simple and racemization-free and gives excellent results with alpha-amino acids, alpha-amino alcohols, dipeptides, alpha-amino carboxamides, and alpha-amino esters.
tert-Butyl 2-substituted 4,6-dioxo-1-piperidinecarboxylates 4 have been prepared in good yield starting from Boc-Asp-O(t)Bu and other beta-amino acids. By analogy with chiral tetramic acids, their reduction by NaBH(4) in CH(2)Cl(2)/AcOH afforded the corresponding cis-4-hydroxy delta-lactams in good yield and stereoselectivity (68-98% de). In the absence of the A(1,3) strain (reduction of 6-substituted 2,4-dioxo-1-piperidines 7), the cis-4-hydroxy isomer was still obtained as the major product but the de values were consistently lower. 4-Hydroxy-6-oxo-1,2-piperidinedicarboxylate 2a, readily accessible from Boc-Asp-O(t)Bu (three steps, 63% overall yield), has proven to be an excellent building block for the synthesis of cis- and trans-4-hydroxypipecolates 17 and 24 (52 and 36% overall yield, respectively) and for the synthesis of a protected 4-hydroxylysine derivative 29 (41% overall yield).
N-Boc-protected-5-substituted delta-lactams were readily prepared from the corresponding beta 3-amino acids. Alkylation reactions of their Na enolates with various electrophiles proceeded in high yields with high facial selectivity. The structure of the alkylation products was confirmed by single-crystal X-ray analysis. This method provides a fast access to optically active alpha, delta-disubstituted delta-amino acids.
4-Amino-2-benzazepin-3-ones have proven very useful for studying the biologically active conformations of peptides. The synthesis of Pht-Aba-Xaa-OH by reaction of the corresponding 1,3-oxazolidin-5-one with trifluoromethanesulfonic acid (TFMSA) has been reported in the literature. However, when this procedure was applied to the preparation of Pht-Hba(Bn)-Gly-OH 8, many byproducts were formed and the yield of the desired aminobenzazepinones 7 and 8 was very low. We report in this paper an efficient methodology for the synthesis of Pht-Hba(2,6-Cl2-Bn)-Gly-OH 17 starting from the commercially available tyrosine. In our procedure, the dipeptide Pht-Tyr(2,6-Cl2-Bn)-Gly-OH 15 is converted to the 1,3-oxazolidin-5-one 16 which then undergoes Friedel-Crafts cyclization in the presence of tin tetrachloride to afford the desired 4-phthalimido-1,3,4,5-tetrahydro-8-(2,6-dichlorobenzyloxy)-2-be nzazepin-3-one 17 in excellent yield.
A practical synthesis of a tripeptide containing a ketomethylene isostere, suitably protected for introduction in Fmoc SPPS, has been carried out for the first time in Fmoc chemistry by using a modified Dakin-West reaction.
A series of conformationally restricted analogs of the hen egg lysozyme (HEL) decapeptide 52-61 in which the conformationally flexible Tyr53 residue was replaced by several more constrained tyrosine and phenylalanine analogs was prepared. Among these tyrosine and phenylalanine analogs were 1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (Htc), 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic), 4-amino- 1,2,4,5-tetrahydro-8-hydroxy-2-benzazepine-3-one (Hba), 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one (Aba), 2-amino-6-hydroxytetralin-2-carboxylic acid (Hat) and 2-amino-5-hydroxyindan-2-carboxylic acid (Hai) in which the rotations around Calpha-Cbeta and Cbeta-Cgamma were restricted because of cyclization of the side-chain to the backbone. Synthesis of Pht-Hba-Gly-OH using a modification of the Flynn and de Laszlo procedure is described. Analogs of beta-methyltyrosine (beta-MeTyr) in which the side-chains were biased to particular side-chain torsional angles because of substitution at the beta-hydrogens were also prepared. These analogs of HEL[52-61] peptide were tested for their ability to bind to the major histocompatibility complex class II I-Ak molecule and to be recognized in this context by two T-cell hybridomas, specific for the parent peptide HEL[52-61]. The data showed that the conformation and also the configuration of the Tyr53 residue influenced both the binding of the peptide to I-Ak and the recognition of the peptide/I-Ak complex by a T-cell receptor.
L. de BROUCKbRE et J. CASlMlR (l) (Bruxelles) ROSUME. -La mdthode de preparation des hydrosols d'or homeodisperses, suggdree par Thiessen, a Btb amelioree. Comme reducteur primaire, on a utilis6 le thiocyanate de potassium plut6t que le phosphore. La seconde reduction a dtB effectude par l'eau oxyghee, et non par le formol comme dans la mbthode primitive. De plus, on a veil16 B ce que la solution rcste constamment alcaline.Le caractere hom6odisperse et la stabilitd des sols ont dt6 mis en evidence par des numerations l'ultramicroscope.SUMMARY. -Thiessen's nuclei method for preparing graded gold sols has been modified. Thiocyanate ions replace phosphorous in the formation of nuclei. As second reducing agent, hydrogen peroxide is suggested instead of formaldehyd. Moreover care must be taken to keep the solution alcaline during the whole procedure.The uniformity of particle size and the stability of the hydrosols have been controlled.
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