Triisobutylaluminium-Mediated Regioselective Protection of Sterically Hindered Amide NH of Cyclo-(AA-Gly): Key Building Block for Next-Generation Peptide Synthesis DOI
Isai Ramakrishna, Tomohiro Hattori, Hisashi Yamamoto

et al.

Synlett, Journal Year: 2023, Volume and Issue: 35(10), P. 1113 - 1120

Published: Nov. 13, 2023

Abstract In this study, we address the challenge of regioselective Boc protection in more sterically hindered amide NH unsymmetrical 2,5-diketopiperazines (DKPs) formed from glycine and various amino acids. Our research introduces a novel technique utilizing cost-effective triisobutylaluminium trimethoxysilane. Notably, trimethoxysilane selectively reacts with less NH, facilitating congested DKPs. The primary objective our work is to develop straightforward scalable approach for synthesis Boc-protected DKPs, focus on addressing steric challenges presented by these compounds. We successfully demonstrate scalability method, enabling variety mono-Fmoc-, Cbz-, Alloc-, EtOCO-protected Furthermore, extend applicability strategy employing it construction pentapeptides through twofold peptide-elongation process. findings reveal versatility efficiency Boc-protection method. Overall, valuable solution DKPs demonstrates its peptide synthesis, showcasing potential further advancements field.

Language: Английский

The role of silicon in drug discovery: a review DOI Creative Commons
Jenny‐Lee Panayides, Darren L. Riley, Felix Hasenmaile

et al.

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(10), P. 3286 - 3344

Published: Jan. 1, 2024

This review aims to highlight the role of silicon in drug discovery.

Language: Английский

Citations

11
Chiral Bisphosphine-Catalyzed Asymmetric Staudinger/aza-Wittig Reaction: An Enantioselective Desymmetrizing Approach to Crinine-Type Amaryllidaceae Alkaloids DOI
Hongzhi Yang, Jingyang Zhang, Sen Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(20), P. 14136 - 14148

Published: April 20, 2024

An unprecedented chiral bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction of 2,2-disubstituted cyclohexane-1,3-diones is reported, enabling the facile access a broad range cis-3a-arylhydroindoles in high yields with excellent enantioselectivities. The key to success this work relies on first application bisphosphine DuanPhos reaction. effective reductive system has been established address challenging PV═O/PIII redox cycle associated catalyst. In addition, comprehensive experimental and computational investigations were carried out elucidate mechanism Leveraging newly developed chemistry, enantioselective total syntheses several crinine-type Amaryllidaceae alkaloids, including (+)-powelline, (+)-buphanamine, (+)-vittatine, (+)-crinane, have accomplished remarkable conciseness efficiency.

Language: Английский

Citations

9
Synthesis of Alkynylsilanes: A Review of the State of the Art DOI
Krzysztof Kuciński

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(11), P. 2382 - 2431

Published: April 12, 2024

Abstract This contribution offers a comprehensive overview of methods for forging sp C−Si bonds. Over time, alkynylsilanes (silylacetylenes), once considered mere byproducts hydrosilylation processes, have become essential building blocks in organic synthesis. literature review traces the evolution their synthesis, from traditional methodologies relying on organolithium and organomagnesium compounds to more advanced cross‐coupling reactions involving hydro‐ carbosilanes. Focused primarily past 25 years (2000–2024), it also extensively references significant historical breakthroughs. By analyzing synthetic methodologies, not only survey current state knowledge but identifies areas improvement. Furthermore, emphasize importance 1‐alkynylsilanes (1‐silyl‐1‐alkynes), selected applications these are highlighted, confirming potential

Language: Английский

Citations

6
On the Use of Triarylsilanols as Catalysts for Direct Amidation of Carboxylic Acids DOI Creative Commons
D. Christopher Braddock, Ben C. Rowley, Paul D. Lickiss

et al.

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(14), P. 9853 - 9869

Published: July 11, 2023

Triarylsilanols have been reported as the first silicon-centered molecular catalysts for direct amidation of carboxylic acids with amines identified after a screen silanols, silanediols, disiloxanediols, and incompletely condensed silsesquioxanes potential homogeneous catalysts. Subsequent synthesis testing various electronically differentiated triarylsilanols tris(p-haloaryl)silanols more active than parent triarylsilanol, where bromide congener is found to be most active. Catalyst decomposition can observed by NMR methods, but RPKA methods reveal that product inhibition operative, tertiary amides are inhibitory secondary amides. Studies using an authentically synthesized triaryl silylester putative intermediate in catalytic system enable plausible mechanism proposed supported computationals.

Language: Английский

Citations

13
Combined Computational and Experimental Study Reveals Complex Mechanistic Landscape of Brønsted Acid-Catalyzed Silane-Dependent P═O Reduction DOI
Jingyang Zhang, Wang‐Yeuk Kong, Wentao Guo

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(20), P. 13983 - 13999

Published: May 13, 2024

The reaction mechanism of Brønsted acid-catalyzed silane-dependent P═O reduction has been elucidated through combined computational and experimental methods. Due to its remarkable chemo- stereoselective nature, the acid/silane system widely employed in organophosphine-catalyzed transformations involving P(V)/P(III) redox cycle. However, full mechanistic profile this type yet be clearly established date. Supported by both DFT studies, our research reveals that likely proceeds mechanisms other than accepted "dual activation mode silyl ester" or "acid-mediated direct activation" mechanism. We propose although may vary with substitution patterns silane species, acid generally activates rather group transition structures. proposed differs significantly from associated traditional C═O reduction. uniqueness originates dominant Si/O═P orbital interactions structures P/H–Si interactions. comprehensive landscape provided us will serve as a guidance for rational design development more efficient systems well novel reactions

Language: Английский

Citations

3
Synthesis of Mono-Boc-2,5-Diketopiperazine: A Key Building Block for Amide and Peptide Synthesis DOI

Isai Ramakrishna,

Alex Boateng, Tomohiro Hattori

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Diketopiperazine (DKP), a versatile scaffold, is extensively used in the synthesis of complex natural products, bioactive molecules, and smart materials organic chemistry. Recently, activated DKPs, such as Boc-DKPs, have emerged key building blocks for peptide elongation synthesis. In this study, we developed facile protocol synthesizing mono-Boc-protected DKPs from readily accessible N-4-methoxybenzyl (N-PMB)-amino acids amino acid methyl esters. This involved sequence reactions encompassing formation dipeptides N-PMB-amino esters, cyclization N-PMB-dipeptides to form PMB-DKPs, Boc-protection subsequent PMB-deprotection PMB-DKP-Boc afford mono-Boc-DKPs. The demonstrated broad substrate scope, accommodating diverse with various side chains, affording mono-Boc-DKPs good yields excellent stereoselectivities (>20:1 dr). synthetic utility was showcased by pentapeptide Boc-l-Tyr(t-Bu)-Gly-l-Phe-Gly-l-Val-OtBu 2-fold two Furthermore, synthesized Leu-enkephalin reacting cyclo(Boc-l-Tyr(t-Bu)-Gly-) H-Gly-l-Phe-l-Leu-Ot-Bu, resulting yield optical purity.

Language: Английский

Citations

0
Enantioselective Deoxygenative Amino-Cyanation of Carboxylic Acids via Ti-Multicatalysis DOI

Giovani Gutierrez,

Jason A. Wilt,

Sher Muhammad

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(44), P. 9442 - 9447

Published: Oct. 28, 2024

Carboxylic acids are valued synthetic building blocks that offer shelf life stability, structural diversity, and wide commercial availability. Despite the remarkable utility of carboxylic acids, a direct enantioselective deoxygenative functionalization remains rare. We present amino-cyanation using novel TiIV-multicatalytic system catalytically modified each C–O bond acid to C–C, C–N, C–H bonds, generating enantio-enriched chiral α-amino nitriles (up 98:2 er).

Language: Английский

Citations

2
Hexylsilane-mediated direct amidation of amino acids with a catalytic amount of 1,2,4-triazole DOI
Tomoya Nobuta,

Nozomi Tsuchiya,

Yutaka Suto

et al.

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 22(4), P. 703 - 707

Published: Nov. 25, 2023

α-Amino amides were synthesized by direct amidation using hexylsilane as a coupling reagent.

Language: Английский

Citations

5
Chiral-Bisphosphine-Catalyzed Asymmetric Staudinger/Aza-Wittig Reaction: Development, Mechanism Study, and Synthetic Application DOI
Yefeng Tang, Hongzhi Yang,

Truc Quynh Nguyen

et al.

Synlett, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 22, 2024

Abstract The enantioselective desymmetrization of 2,2-disubstituted cyclohexane-1,3-diones has been realized through an unprecedented chiral-bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction. key to this work’s success lies in utilizing electronically rich and sterically hindered chiral bisphosphine reagent, namely DuanPhos, as a catalyst. In addition, unique reductive system was established address the requisite PIII/PV = O redox cycle. mechanism reaction elucidated combined computational experimental studies. Several crinine-type amaryllidaceae alkaloids have synthesized concisely, hinging on newly developed methodology.

Language: Английский

Citations

1
Triisobutylaluminium-Mediated Regioselective Protection of Sterically Hindered Amide NH of Cyclo-(AA-Gly): Key Building Block for Next-Generation Peptide Synthesis DOI
Isai Ramakrishna, Tomohiro Hattori, Hisashi Yamamoto

et al.

Synlett, Journal Year: 2023, Volume and Issue: 35(10), P. 1113 - 1120

Published: Nov. 13, 2023

Abstract In this study, we address the challenge of regioselective Boc protection in more sterically hindered amide NH unsymmetrical 2,5-diketopiperazines (DKPs) formed from glycine and various amino acids. Our research introduces a novel technique utilizing cost-effective triisobutylaluminium trimethoxysilane. Notably, trimethoxysilane selectively reacts with less NH, facilitating congested DKPs. The primary objective our work is to develop straightforward scalable approach for synthesis Boc-protected DKPs, focus on addressing steric challenges presented by these compounds. We successfully demonstrate scalability method, enabling variety mono-Fmoc-, Cbz-, Alloc-, EtOCO-protected Furthermore, extend applicability strategy employing it construction pentapeptides through twofold peptide-elongation process. findings reveal versatility efficiency Boc-protection method. Overall, valuable solution DKPs demonstrates its peptide synthesis, showcasing potential further advancements field.

Language: Английский

Citations

3