- Solid-phase synthesis of 3,5-disubstituted 2,3-dihydro-1,5- benzothiazepin-4(5H)-ones
-
A solid-phase route affording novel 3,5-disubstituted 1,5- benzothiazepin-4(5H)-ones in optically pure form has been enabled. S(N)Ar reaction of polymer-bound 4-fluoro-3-nitrobenzoic acid, 12, with L-Fmoc- cysteine, L-13, under basic conditions, followed by tin(II) chloride mediated nitro group reduction, furnished the primary aniline 15. Reductive alkylation of 15 to the corresponding secondary anilines 17 was shown to be feasible for a wide range of aldehydes, using an optimized solvent system composed of CH(OMe)3, DMF, MeOH, and HOAc, with NaCNBH3 as the reducing agent. In cases of enolizable aldehydes, benzotriazole was found to be a beneficial additive for the suppression of side-products due to imine-enamine tautomerization. Subsequent cyclization of the secondary anilines 17 using DIC in apolar solvents furnished the corresponding N(5)-alkylated 1,5-benzothiazepin-4- ones 19. Following Fmoc removal from 19, the primary amino group was finally reacted with carboxylic acids, isocyanates, sulfonyl chlorides, or aldehydes to afford the respective amides 32, ureas 33, sulfonamides 34, or secondary amines 35. Performing the synthesis with the D-form of Fmoc-cysteine, D-13, resulted in the corresponding antipodal products, with no detectable scrambling at C(3). The solid-phase assembly of 1,5-benzothiazepin-4-ones was also shown to be compatible with chemical encoding based on dialkylamine tags, enabling the construction of large combinatorial libraries of the title compounds.
- Schwarz, Matthias K.,Tumelty, David,Gallop, Mark A.
-
-
Read Online
- Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
-
Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
- Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
-
p. 1080 - 1090
(2020/05/25)
-
- A compound and its preparation process and method for producing a polypeptide using the same
-
The invention discloses a compound, a preparation method thereof and a method for preparing a polypeptide by virtue of the compound. The compound has the structure specified in the description, wherein the N-terminal cysteine of the polypeptide can be protected by virtue of the compound, thus shielding the activity of the N-terminal cysteine, then connection for more (greater than or equal to 3) polypeptide segments can be realized when the polypeptide segments are connected to prepare proteins, i.e., separation and purification treatment is not needed after every two polypeptide segments are connected, and connection with the next polypeptide segment can be directly carried out after the shielding is removed.
- -
-
Paragraph 0121; 0122
(2016/12/01)
-