A novel thiochromone-type photolabile protecting group for carbonyl compounds

Sugiura, Ryo; Kozaki, Rikio; Kitani, Satoru; Gosho, Yoshinori; Tanimoto, Hiroki; Nishiyama, Yasuhiro; Morimoto, Tsumoru; Kakiuchi, Kiyomi

doi:10.1016/j.tet.2013.03.022

Cited by 22 publications

(9 citation statements)

References 12 publications

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“…As an alternative, we sought a ketone protecting group that would be directly and cleanly removed under photochemical conditions. Photolabile protecting groups for ketones include cyclic acetals bearing a 2-nitro group, [20] [21] coumarine derivative used for 1-or 2-photon deprotection, [22] thiochromone-type photolabile protecting group, [23] and 5-methoxy salicylic alcohol derivative. [24] During the course of our development of acid-labile protecting groups for peptide a-ketoacids, we identified 6membered ring acetals bearing a gem-dimethyl group as the best choices in terms of introduction of the protecting group, stability to Fmoc-SPPS, and epimerization-free deprotection.…”

Section: Development Of Photoprotected A-ketoacidsmentioning

confidence: 99%

Photoprotected Peptide α‐Ketoacids and Hydroxylamines for Iterative and One‐Pot KAHA Ligations: Synthesis of NEDD8

Thuaud

Rohrbacher

Zwicky

et al. 2016

Helvetica Chimica Acta

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The convergent synthesis of proteins by multiple ligations requires segments protected at the N-and/or C-terminus with masking groups that are orthogonal to the acid-and base-labile protecting groups used in Fmoc-SPPS. They must be stable to solid-phase peptide synthesis, HPLC purification, and ligation conditions and easily removed in the presence of unprotected side chains. In this report, we document photolabile protecting groups for both a-ketoacids and hydroxylamines, the key functional groups employed in the a-ketoacid-hydroxylamine (KAHA) ligation. The novel photoprotected a-ketoacid is easily installed onto numerous different C-terminal peptide aketoacids and removed by UV light under aqueous conditions. These advances were applied to the one-pot synthesis of NEDD8, an important modifier protein, by three different convergent routes. These new protecting groups provide greater flexibility on the order of fragment assembly and reduce the number of reaction and purification steps needed for protein synthesis with the KAHA ligation.Scheme 1. Protection of a-ketoacids as photolabile cyclic acetals.Helv. Chim. Acta 2016, 99, 868 -894 In order to utilize the photoprotected a-ketoacids for iterative segment ligations, we applied them to the Fmoc-SPPS of C-terminal protected peptides. Using the same linker we previously reported for traceless preparation of C-terminal peptide a-ketoacids, we Scheme 2. Synthesis of enantiomerically enriched protecting group 2 and determination of the absolute configuration of acetal derivative 7 by single-crystal X-ray diffraction (thermal ellipsoids shown in the ORTEP model are set at a 50% probability level). 870Helv. Chim. Acta 2016, 99, 868 -894 www.helv.wiley.com a Determined by chiral SFC (column Chiralpak ADH) with detection at 220 nm. b After recrystallization from hexanes/AcOEt 25:1 (74% recrystallization yield). CatBH = catecholborane.Scheme 5. Synthesis of photoprotected (S)-5-oxaproline 21.Helv. Chim. Acta 2016, 99, 868 -894 873 Scheme 6. One-pot synthesis of NEDD8 in the N-to C-direction using a photoprotected tyrosine a-ketoacid.Helv. Chim. Acta 2016, 99, 868 -894 875Scheme 8. One-pot convergent synthesis of NEDD8 from four segments.Helv. Chim. Acta 2016, 99, 868 -894 877

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Section: Development Of Photoprotected A-ketoacidsmentioning

confidence: 99%

Photoprotected Peptide α‐Ketoacids and Hydroxylamines for Iterative and One‐Pot KAHA Ligations: Synthesis of NEDD8

Thuaud

Rohrbacher

Zwicky

et al. 2016

Helvetica Chimica Acta

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“…They are very promising compounds, which exhibit a variety of pharmacological acivities . In addition, their oxidized derivatives have been used as human cytomegalovirus protease inhibitors, as well as photolabile protecting groups for phosphate compounds . Because of their importance, a numerous of synthetic pathways have been explored for the preparation of thiochromenones .…”

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confidence: 99%

Nickel-Catalyzed One-Pot Carbonylative Synthesis of 2-Mono- and 2,3-Disubstituted Thiochromenones from 2-Bromobenzenesulfonyl Chlorides and Alkynes

Wang

Bao

et al. 2021

Org. Lett.

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A nickel-catalyzed one-pot carbonylation reaction of 2-bromobenzenesulfonyl chlorides with alkynes for the synthesis of thiochromenones has been established. Both terminal and internal alkynes were suitable substrates in this carbonylative transformation, and a broad range of 2-mono- and 2,3-disubstituted thiochromenone products were obtained in moderate to good yields with quite high functional group compatibility. Notably, this procedure presents the first example of nickel-catalyzed carbonylative synthesis of thiochromenones with 2-bromobenzenesulfonyl chlorides as a promising sulfur precursor.

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“…Thiochromenones are important sulfur-containing heterocycles present in various naturally occurring products and biological active chemicals . Oxidized derivatives of thiochromenones have been used as cytomegalovirus protease inhibitors for humans as well as protecting groups for phosphate compounds . Considering their importance, different pathways have been established for their preparation .…”

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confidence: 99%

Carbonylative Synthesis of 3-Substituted Thiochromenones via Rhodium-Catalyzed [3 + 2 + 1] Cyclization of Different Aromatic Sulfides, Alkynes, and Carbon Monoxide

Zhu

2018

J. Org. Chem.

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A novel thiochromone-type photolabile protecting group for carbonyl compounds

Cited by 22 publications

References 12 publications

Photoprotected Peptide α‐Ketoacids and Hydroxylamines for Iterative and One‐Pot KAHA Ligations: Synthesis of NEDD8

Photoprotected Peptide α‐Ketoacids and Hydroxylamines for Iterative and One‐Pot KAHA Ligations: Synthesis of NEDD8

Nickel-Catalyzed One-Pot Carbonylative Synthesis of 2-Mono- and 2,3-Disubstituted Thiochromenones from 2-Bromobenzenesulfonyl Chlorides and Alkynes

Carbonylative Synthesis of 3-Substituted Thiochromenones via Rhodium-Catalyzed [3 + 2 + 1] Cyclization of Different Aromatic Sulfides, Alkynes, and Carbon Monoxide

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