Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives

Chirality has garnered significant attention in the scientific community since its discovery by Louis Pasteur over a century ago. It has been showing a profound impact on chemical, biomedical, and materials sciences. Significant progress has been made in controlling molecular chirality, as evidenced...

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Main Authors: Anis U. Rahman, Yu Wang, Ting Xu, Kambham Devendra Reddy, Shengzhou Jin, Jasmine X. Yan, Qingkai Yuan, Daniel Unruh, Ruibin Liang, Guigen Li
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2024-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0550
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author Anis U. Rahman
Yu Wang
Ting Xu
Kambham Devendra Reddy
Shengzhou Jin
Jasmine X. Yan
Qingkai Yuan
Daniel Unruh
Ruibin Liang
Guigen Li
author_facet Anis U. Rahman
Yu Wang
Ting Xu
Kambham Devendra Reddy
Shengzhou Jin
Jasmine X. Yan
Qingkai Yuan
Daniel Unruh
Ruibin Liang
Guigen Li
author_sort Anis U. Rahman
collection DOAJ
description Chirality has garnered significant attention in the scientific community since its discovery by Louis Pasteur over a century ago. It has been showing a profound impact on chemical, biomedical, and materials sciences. Significant progress has been made in controlling molecular chirality, as evidenced by the several Nobel Prizes in chemistry awarded in this area, particularly for advancements in the asymmetric catalytic synthesis of molecules with central and axial chirality. However, the exploration of new types of chirality has been largely stagnant for more than half a century, likely due to the complexity and challenges inherent in this field. In this work, we present the discovery of a novel type of chirality—staircase chirality as inspired by the design and synthesis of unnatural amino acid derivatives. The architecture of staircase chirality is characterized by 2 symmetrical phenyl rings anchored by a naphthyl pier, with the rings asymmetrically displaced due to the influence of chiral auxiliaries at their para positions. This unique staircase chiral framework has been thoroughly characterized using spectroscopic techniques, with its absolute configuration definitively confirmed by x-ray diffraction analysis. Remarkably, one of the staircase molecules exhibits 4 distinct types of chirality: central, orientational, turbo, and staircase chirality, a combination that has not been previously documented in the literature. Computational studies using density functional theory (DFT) calculations were conducted to analyze the relative energies of individual staircase isomers, and the results are in agreement with our experimental findings. We believe that this discovery will open up a new research frontier in asymmetric synthesis and catalysis, with the potential to make a substantial impact on the fields of chemistry, medicine, and materials science.
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spelling doaj-art-a46bdd5fd3d94a049c4e76035bb7f9cf2025-08-20T02:52:41ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742024-01-01710.34133/research.0550Discovery of Staircase Chirality through the Design of Unnatural Amino Acid DerivativesAnis U. Rahman0Yu Wang1Ting Xu2Kambham Devendra Reddy3Shengzhou Jin4Jasmine X. Yan5Qingkai Yuan6Daniel Unruh7Ruibin Liang8Guigen Li9School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA.School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA.Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA.Iowa Advanced Technology Laboratories, University of Iowa, Iowa City, IA 52242, USA.Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA.School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.Chirality has garnered significant attention in the scientific community since its discovery by Louis Pasteur over a century ago. It has been showing a profound impact on chemical, biomedical, and materials sciences. Significant progress has been made in controlling molecular chirality, as evidenced by the several Nobel Prizes in chemistry awarded in this area, particularly for advancements in the asymmetric catalytic synthesis of molecules with central and axial chirality. However, the exploration of new types of chirality has been largely stagnant for more than half a century, likely due to the complexity and challenges inherent in this field. In this work, we present the discovery of a novel type of chirality—staircase chirality as inspired by the design and synthesis of unnatural amino acid derivatives. The architecture of staircase chirality is characterized by 2 symmetrical phenyl rings anchored by a naphthyl pier, with the rings asymmetrically displaced due to the influence of chiral auxiliaries at their para positions. This unique staircase chiral framework has been thoroughly characterized using spectroscopic techniques, with its absolute configuration definitively confirmed by x-ray diffraction analysis. Remarkably, one of the staircase molecules exhibits 4 distinct types of chirality: central, orientational, turbo, and staircase chirality, a combination that has not been previously documented in the literature. Computational studies using density functional theory (DFT) calculations were conducted to analyze the relative energies of individual staircase isomers, and the results are in agreement with our experimental findings. We believe that this discovery will open up a new research frontier in asymmetric synthesis and catalysis, with the potential to make a substantial impact on the fields of chemistry, medicine, and materials science.https://spj.science.org/doi/10.34133/research.0550
spellingShingle Anis U. Rahman
Yu Wang
Ting Xu
Kambham Devendra Reddy
Shengzhou Jin
Jasmine X. Yan
Qingkai Yuan
Daniel Unruh
Ruibin Liang
Guigen Li
Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives
Research
title Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives
title_full Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives
title_fullStr Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives
title_full_unstemmed Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives
title_short Discovery of Staircase Chirality through the Design of Unnatural Amino Acid Derivatives
title_sort discovery of staircase chirality through the design of unnatural amino acid derivatives
url https://spj.science.org/doi/10.34133/research.0550
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