scholarly journals Pentanidium-Catalyzed Direct Assembly of Vicinal All-Carbon Quaternary Stereocenters through C(sp3)-C(sp3) Bond Formation

2021 ◽  
Author(s):  
Choon-Hong Tan ◽  
Xu Ban ◽  
Yifan Fan ◽  
Tuan-Khoa Kha ◽  
Richmond Lee ◽  
...  
Keyword(s):  
Bond Formation ◽  
Direct Assembly ◽  
Tertiary Carbon ◽  
Asymmetric Coupling ◽  
Catalytic Asymmetric ◽  
Quaternary Stereocenters ◽  
Straightforward Approach

Abstract The stereoselective construction of vicinal all-carbon quaternary stereocenters has long been a formidable synthetic challenge. Direct asymmetric coupling of a tertiary carbon nucleophile with a tertiary carbon electrophile is the most straightforward approach but it is sterically and energetically disfavored. Herein, we described a catalytic asymmetric substitution, where racemic tertiary bromides directly couple with racemic secondary or tertiary carbanion, creating a series of congested carbon (sp3)-carbon(sp3) bonds, including isolated all-carbon quaternary stereocenters, vicinal tertiary/all-carbon quaternary stereocenters and vicinal all-carbon quaternary stereocenters. This double stereoconvergent process, using pentanidium as catalyst, affords substituted products in good enantioselectivities and diastereoselectivities.

scholarly journals Tailoring Tryptophan Synthase TrpB for Selective Quaternary Carbon Bond Formation

2019 ◽  
Author(s):  
Markus Dick ◽  
Nicholas S. Sarai ◽  
Michael W. Martynowycz ◽  
Tamir Gonen ◽  
Frances H. Arnold
Keyword(s):  
Condensation Reaction ◽  
Bond Formation ◽  
Tryptophan Synthase ◽  
Indole Derivatives ◽  
Quaternary Carbon ◽  
Noncanonical Amino Acids ◽  
Carbon Bond ◽  
E Coli ◽  
Tertiary Carbon ◽  
Quaternary Stereocenters

<div><div><div><p>We previously engineered the tryptophan synthase beta-subunit (TrpB), which catalyzes the condensation reaction between L-serine and indole to form L-tryptophan, to synthesize a range of modified tryptophans from serine and indole derivatives. In this study, we used directed evolution to engineer TrpB to accept 3-substituted oxindoles and form C–C bonds leading to new quaternary stereocenters. At first, the TrpBs that could use 3-substituted oxindoles preferentially formed N–C bonds by attacking the oxindole N<sub>1 </sub>atom. We found, however, that protecting the nitrogen encouraged evolution towards C-alkylation, which persisted even when this protection was removed. After seven rounds of evolution leading to a 400-fold improvement in activity, variant <i>Pf</i><sub>quat</sub> efficiently alkylates 3-substituted oxindoles to selectively form new stereocenters at the γ-position of the amino acid products. The configuration of the new γ-stereocenter of one of the products was determined from the crystal structure obtained by microcrystal electron diffraction (MicroED). Substrates structurally related to 3-methyloxindole such as lactones and ketones can also be used by the enzyme for quaternary carbon bond formation, where the biocatalyst exhibits excellent regioselectivity for the tertiary carbon atom. Highly thermostable and expressed at > 500 mg/L <i>E. coli</i> culture, TrpB <i>Pf</i><sub>quat </sub>provides an efficient and environmentally-friendly platform for the preparation of noncanonical amino acids bearing quaternary carbons.</p></div></div></div>

scholarly journals Pentanidium-Catalyzed Direct Assembly of Vicinal All-Carbon Quaternary Stereocenters through C(sp 3 )-C(sp 3 ) Bond Formation

CCS Chemistry ◽  
2021 ◽  
pp. 1-21
Author(s):  
Xu Ban ◽  
Yifan Fan ◽  
Tuan-Khoa Kha ◽  
Richmond Lee ◽  
Choon Wee Kee ◽  
...  
Keyword(s):  
Bond Formation ◽  
Direct Assembly ◽  
Quaternary Stereocenters

scholarly journals Tailoring Tryptophan Synthase TrpB for Selective Quaternary Carbon Bond Formation

2019 ◽  
Author(s):  
Markus Dick ◽  
Nicholas S. Sarai ◽  
Michael W. Martynowycz ◽  
Tamir Gonen ◽  
Frances H. Arnold
Keyword(s):  
Condensation Reaction ◽  
Bond Formation ◽  
Tryptophan Synthase ◽  
Indole Derivatives ◽  
Quaternary Carbon ◽  
Noncanonical Amino Acids ◽  
Carbon Bond ◽  
E Coli ◽  
Tertiary Carbon ◽  
Quaternary Stereocenters

<div><div><div><p>We previously engineered the tryptophan synthase beta-subunit (TrpB), which catalyzes the condensation reaction between L-serine and indole to form L-tryptophan, to synthesize a range of modified tryptophans from serine and indole derivatives. In this study, we used directed evolution to engineer TrpB to accept 3-substituted oxindoles and form C–C bonds leading to new quaternary stereocenters. At first, the TrpBs that could use 3-substituted oxindoles preferentially formed N–C bonds by attacking the oxindole N<sub>1 </sub>atom. We found, however, that protecting the nitrogen encouraged evolution towards C-alkylation, which persisted even when this protection was removed. After seven rounds of evolution leading to a 400-fold improvement in activity, variant <i>Pf</i><sub>quat</sub> efficiently alkylates 3-substituted oxindoles to selectively form new stereocenters at the γ-position of the amino acid products. The configuration of the new γ-stereocenter of one of the products was determined from the crystal structure obtained by microcrystal electron diffraction (MicroED). Substrates structurally related to 3-methyloxindole such as lactones and ketones can also be used by the enzyme for quaternary carbon bond formation, where the biocatalyst exhibits excellent regioselectivity for the tertiary carbon atom. Highly thermostable and expressed at > 500 mg/L <i>E. coli</i> culture, TrpB <i>Pf</i><sub>quat </sub>provides an efficient and environmentally-friendly platform for the preparation of noncanonical amino acids bearing quaternary carbons.</p></div></div></div>

Recent Advances in C–Br Bond Formation

Synlett ◽  
2021 ◽  
Author(s):  
Ying-Yeung Yeung ◽  
Jonathan Wong
Keyword(s):  
Organic Synthesis ◽  
Aromatic Compounds ◽  
Bond Formation ◽  
Cross Coupling ◽  
Catalytic Site ◽  
Atom Transfer ◽  
Bond Forming ◽  
Recent Advances ◽  
Catalytic Asymmetric ◽  
Site Selective

AbstractOrganobromine compounds are extremely useful in organic synthesis. In this perspective, a focused discussion on some recent advancements in C–Br bond-forming reactions is presented.1 Introduction2 Selected Recent Advances2.1 Catalytic Asymmetric Bromopolycyclization of Olefinic Substrates2.2 Catalytic Asymmetric Intermolecular Bromination2.3 Some New Catalysts and Reagents for Bromination2.4 Catalytic Site-Selective Bromination of Aromatic Compounds2.5 sp3 C–H Bromination via Atom Transfer/Cross-Coupling3 Outlook

Vinylogy in nitronates: utilization of α-aryl conjugated nitroolefins as a nucleophile for a highly stereoselective aza-Henry reaction

2015 ◽  
Vol 51 (21) ◽  
pp. 4437-4439 ◽  
Author(s):  
Keigo Oyaizu ◽  
Daisuke Uraguchi ◽  
Takashi Ooi
Keyword(s):  
Bond Formation ◽  
Henry Reaction ◽  
Quaternary Stereocenters

Vinylogous nitronates generated from α,β-disubstituted nitroolefins undergo stereoselective bond formation with aldimines at the sterically encumbered α-position, establishing contiguous tertiary–quaternary stereocenters.

scholarly journals Catalytic asymmetric carbon–carbon bond formation using alkenes as alkylmetal equivalents

2012 ◽  
Vol 4 (8) ◽  
pp. 649-654 ◽  
Author(s):  
Rebecca M. Maksymowicz ◽  
Philippe M. C. Roth ◽  
Stephen P. Fletcher
Keyword(s):  
Bond Formation ◽  
Carbon Bond ◽  
Carbon Carbon Bond ◽  
Catalytic Asymmetric ◽  
Asymmetric Carbon

scholarly journals Catalytic Asymmetric CN Bond Formation: Phosphine-Catalyzed Intra- and Intermolecular γ-Addition of Nitrogen Nucleophiles to Allenoates and Alkynoates

2013 ◽  
Vol 52 (9) ◽  
pp. 2525-2528 ◽  
Author(s):  
Rylan J. Lundgren ◽  
Ashraf Wilsily ◽  
Nicolas Marion ◽  
Cong Ma ◽  
Ying Kit Chung ◽  
...  
Keyword(s):  
Bond Formation ◽  
Catalytic Asymmetric ◽  
Nitrogen Nucleophiles

scholarly journals Highly Enantioselective Construction of Quaternary Stereocenters onβ-Keto Esters by Phase-Transfer Catalytic Asymmetric Alkylation and Michael Reaction

2003 ◽  
Vol 115 (34) ◽  
pp. 4111-4111 ◽  
Author(s):  
Takashi Ooi ◽  
Takashi Miki ◽  
Mika Taniguchi ◽  
Misato Shiraishi ◽  
Mifune Takeuchi ◽  
...  
Keyword(s):  
Michael Reaction ◽  
Phase Transfer ◽  
Asymmetric Alkylation ◽  
Keto Esters ◽  
Catalytic Asymmetric ◽  
Quaternary Stereocenters

scholarly journals Synthesis of Adjacent Quaternary Stereocenters by Catalytic Asymmetric Allylboration

2015 ◽  
Vol 137 (35) ◽  
pp. 11262-11265 ◽  
Author(s):  
Rauful Alam ◽  
Tobias Vollgraff ◽  
Lars Eriksson ◽  
Kálmán J. Szabó
Keyword(s):  
Catalytic Asymmetric ◽  
Quaternary Stereocenters
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