1. Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid
Dong Cai, ZhiHua Zhang, Yufan Meng, KaiLi Zhu, LiYi Chen, ChangXiang Yu, ChangWei Yu, ZiYi Fu, DianShen Yang, YiXia Gong Beilstein J Org Chem. 2020 Apr 21;16:798-808. doi: 10.3762/bjoc.16.73. eCollection 2020.
In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures for the construction of important intermediate 8 are discussed. One procedure involves the amidation of 1-Boc-piperazine with 3-acetyl-18β-glycyrrhetinic acid, prepared by the reaction of 18β-glycyrrhetinic acid with acetic anhydride without any solvent at 130 °C. The other procedure to prepare compound 8 involves the amidation of 18β-glycyrrhetinic acid followed by the esterification with acetic anhydride. Finally, compound 8 underwent N-Boc deprotection to prepare product 4. To ascertain the scope of the reaction, another C-3 ester derivative 17 was tested under the optimized reaction conditions. Furthermore, the reasons for the appearance of byproducts were elucidated. Crystallographic data of a selected piperazinyl amide is reported.
2. Direct Synthesis of α-Sulfenylated Ketones under Electrochemical Conditions
Aline A N de Souza, Aloisio de A Bartolomeu, Timothy J Brocksom, Timothy Noël, Kleber T de Oliveira J Org Chem. 2022 May 6;87(9):5856-5865. doi: 10.1021/acs.joc.2c00147. Epub 2022 Apr 13.
We investigated the electrochemical sulfenylation reaction in both batch and continuous flow regimes, involving thiophenols/thiols and enol-acetates to yield α-sulfenylated ketones, without using additional oxidants or catalysts. Studies with different electrolytes were also performed, revealing that quaternary ammonium salts are the best mediators for this reaction. Notably, during the study of the reaction scope, a Boc-cysteine proved to be extremely tolerant to our protocol, thus increasing its relevance. The methodology also proved to be scalable in both batch and continuous flow conditions, opening up possibilities for further studies since these relevant functional groups are important moieties in organic synthesis.
3. 2-Methoxy-4-methylsulfinylbenzyl Alcohol as a Safety-Catch Linker for the Fmoc/ t Bu Solid-Phase Peptide Synthesis Strategy
K P Nandhini, Fernando Albericio, Beatriz G de la Torre J Org Chem. 2022 Aug 5;87(15):9433-9442. doi: 10.1021/acs.joc.2c01057. Epub 2022 Jul 8.
Fmoc and Boc group are the two main groups used to protect the α-amino function in Solid-Phase Peptide Synthesis (SPPS). In this regard, the use of the Mmsb linker allows the combination of these two groups. Peptide-O-Mmsb-Resin is stable to the piperidine and trifluoroacetic acid (TFA) treatment used to remove Fmoc and Boc, respectively. The peptide is detached in a two-step protocol, namely reduction of the sulfoxide to the sulfide with Me3SiCl and Ph3P, and then treatment with TFA. The advantage of this strategy has been demonstrated by the following: preparation of peptide with no diketopiperazine formation in sequences prone to this side reaction; on-resin cyclization without the concourse of common organic reagents such as Pd(0) but of difficult use in a biological laboratory; and on-resin disulfide formation in a total side-chain unprotected peptide. The use of Mmsb linker together with Msib (4-(methylsulfinyl)benzyl) and Msbh (4,4'-bis(methylsulfinyl)benzhydryl) described in the accompanying manuscript add a fourth dimension to the SPPS protecting group scheme.
