1.Controllable Phase Separation by Boc-Modified Lipophilic Acid as a Multifunctional Extractant.
Tao K1, Adler-Abramovich L1,2, Gazit E1,3. Sci Rep. 2015 Dec 2;5:17509. doi: 10.1038/srep17509.
While phase separation of immiscible liquid-liquid systems has become increasingly significant in diverse areas, the irreversible nature limits their further application in controllable extraction-concentration or capture-release fields. There is a need for the development of simple, efficient and reversible methods for numerous research and industrial extraction and separation applications. We envisioned Boc-modified lipophilic acids as a simple model for such use based on the studies of the multi-phase transitions of Boc-modified supramolecular polymeric systems. Here, we demonstrate that in the presence of Boc-7-aminoheptanoic acid (Boc-7), phase separation occurs in mixtures of miscible organic solvent and water. The separation behavior was confirmed by differential colorimetric development in aqueous and organic phases using methyl orange staining assays. Component substitution experiments verified that the phase separation results from the subtle balance between the aggregation and the solvation forces of Boc-7, and is reversible by adjusting the solution pH.
2.Development of a sufficiently reactive thioalkylester involving the side-chain thiol of cysteine applicable for kinetically controlled ligation.
Tsuda S1, Mochizuki M1, Nishio H1,2, Yoshiya T1, Nishiuchi Y1. Biopolymers. 2015 Nov 19. doi: 10.1002/bip.22783. [Epub ahead of print]
Nα -Trifluoroacetyl-Cys-Leu-NH2 (TfaC-Leu-NH2 ) was incorporated into thioesters through its side-chain thiol group to develop a more reactive peptide-thioester than the commonly used peptide-3-mercaptopropionic acid (MPA)-thioester. The TfaC-thioester could be readily synthesized by solid-phase peptide synthesis (SPPS) with Boc chemistry using in situ neutralization protocols in sufficient yield without any side reaction associated with the use of TfaC. This thioester proved to display a much higher reactivity in the thiol-free native chemical ligation (NCL) reaction than the MPA-thioester, and to be comparable to the thioarylester, such as the 4-mercaptophenylacetic acid (MPAA)-thioester, in terms of the ligation rate. We were able to demonstrate the usefulness of the TfaC-thioester by using it to synthesize neuromedin S via a one-pot sequential NCL approach followed by desulfurization. This article is protected by copyright. All rights reserved.
3.Crystal structure of Boc-(S)-ABOC-(S)-Ala-(S)-ABOC-(S)-Phe-OBn chloro-form monosolvate.
Wenger E1, Moulat L2, Legrand B2, Amblard M2, Calmès M2, Didierjean C1. Acta Crystallogr E Crystallogr Commun. 2015 Sep 17;71(Pt 10):1193-5. doi: 10.1107/S2056989015016941. eCollection 2015.
In the title compound, phenyl (S)-2-[(S)-(1-{2-[(S)-(1-{[(tert-but-oxy)carbon-yl]amino}-bicyclo-[2.2.2]octan-2-yl)formamido]-propanamido}-bicyclo-[2.2.2]octan-2-yl)formamido]-3-phenyl-propano-ate chloro-form monosolvate, C42H56N4O7·CHCl3, the α,β-hybrid peptide contains two non-proteinogenic amino acid residues of (S)-1-amino-bicyclo-[2.2.2]octane-2-carb-oxy-lic acid [(S)-ABOC], two amino acid residues of (S)-2-amino-propanoic acid [(S)-Ala] and (S)-2-amino-3-phenyl-propanoic acid [(S)-Phe], and protecting groups of tert-but-oxy-carbonyl (Boc) and benzyl ester (OBn). The tetra-mer folds into a right-handed mixed 11/9 helix stabilized by intra-molecular i,i + 3 and i,i - 1 C=O⋯H-N hydrogen bonds. In the crystal, the oligomers are linked by N-H⋯O=C hydrogen bonds into chains along the a-axis direction. The chloro-form solvent mol-ecules are inter-calated between the folded chains via C-H⋯O=C inter-actions.
4.Asymmetric synthesis of syn-propargylamines and unsaturated β-amino acids under Brønsted base catalysis.
Wang Y1, Mo M1, Zhu K1, Zheng C2, Zhang H1, Wang W3, Shao Z1. Nat Commun. 2015 Oct 1;6:8544. doi: 10.1038/ncomms9544.
Propargylamines are important intermediates for the synthesis of polyfunctional amino derivatives and natural products and biologically active compounds. The classic method of synthesizing chiral propargylamines involves the asymmetric alkynylation of imines. Here, we report a significant advance in the catalytic asymmetric Mannich-type synthesis of propargylamines through catalytic asymmetric addition of carbon nucleophiles to C-alkynyl imines, culminating in a highly syn-selective catalytic asymmetric Mannich reaction of C-alkynyl imines that provide syn-configured propargylamines with two adjacent stereogenic centres and a transition metal-free organocatalytic asymmetric approach to β-alkynyl-β-amino acids with high efficiency and practicality, via a chiral Brønsted base-catalysed asymmetric Mannich-type reaction of in situ generated challenging N-Boc C-alkynyl imines from previously unreported C-alkynyl N-Boc-N,O-acetals, with α-substituted β-keto esters and less-acidic malonate (thio)esters as nucleophiles, respectively.
