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Engineering Heme Proteins for C(Sp³)-H Primary Amination /

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Engineering Heme Proteins for C(Sp³)-H Primary Amination // Shilong Gao.
Author:	Gao, Shilong,
Description:	1 electronic resource (428 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-06, Section: B.
基督教聖經之智慧書導讀 :	Primary amine is one of the most prevalent moieties in synthetic intermediates and pharmaceutical compounds. The preparation of aliphatic primary amines via C−H functionalization would provide direct access to the nitrogen-containing compounds from hydrocarbon substrates. While the enzymatic oxyfunctionalization of C-H bonds is well established, the analogous strategy for nitrogen incorporation is unknown in Nature. Likewise, a synthetic method for selective primary amination of aliphatic C-H bonds remains elusive. Combining chemical intuition and inspiration from Nature, chemists and protein engineers have created new heme-containing enzymes for the C(sp³)-H primary amination via directed evolution. This thesis describes some of the efforts in the continued pursuit of these new-to-nature reactions. Chapter I discusses directed evolution in the context of biocatalysis, the strategies for introducing new-to-nature chemistry in enzymes, the discovery of nitrene transferases from the cytochrome P450 monooxygenase, and finally, the development of C(sp³)-H primary aminases. Chapter II details the discovery and engineering of serine-ligated cytochrome P411 enzymes that catalyze the first primary amination of C(sp³)-H bonds with excellent selectivity, affording a broad scope of enantioenriched primary amines. Chapter III demonstrates that these new-to-nature nitrene transferases were engineered to aminate and amidate unactivated, unbiased C(sp³)-H bonds with unprecedented selectivity. In Chapter IV, engineered protoglobins are shown to utilize hydroxylamine (NH₂OH) for nitrene transfer reactions, including benzylic C-H primary amination and styrene aminohydroxylation. Overall, these new-to-nature reactions can be considered the nitrogen analogs to the C-H oxidation chemistry performed by monooxygenases and peroxygenases. By offering a direct path from saturated precursors, these enzymes present a new biochemical logic for accessing nitrogen-containing compounds. Finally, this work hints at the possible future discovery of natural enzymes that use hydroxylamine precursors for amination chemistry.
Contained By:	Dissertations Abstracts International85-06B.
Subject:	Pharmaceutical sciences. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30750659
ISBN:	9798381032376

Engineering Heme Proteins for C(Sp³)-H Primary Amination /
Gao, Shilong,

Engineering Heme Proteins for C(Sp³)-H Primary Amination /Shilong Gao. - 1 electronic resource (428 pages)

Source: Dissertations Abstracts International, Volume: 85-06, Section: B.

Primary amine is one of the most prevalent moieties in synthetic intermediates and pharmaceutical compounds. The preparation of aliphatic primary amines via C−H functionalization would provide direct access to the nitrogen-containing compounds from hydrocarbon substrates. While the enzymatic oxyfunctionalization of C-H bonds is well established, the analogous strategy for nitrogen incorporation is unknown in Nature. Likewise, a synthetic method for selective primary amination of aliphatic C-H bonds remains elusive. Combining chemical intuition and inspiration from Nature, chemists and protein engineers have created new heme-containing enzymes for the C(sp³)-H primary amination via directed evolution. This thesis describes some of the efforts in the continued pursuit of these new-to-nature reactions. Chapter I discusses directed evolution in the context of biocatalysis, the strategies for introducing new-to-nature chemistry in enzymes, the discovery of nitrene transferases from the cytochrome P450 monooxygenase, and finally, the development of C(sp³)-H primary aminases. Chapter II details the discovery and engineering of serine-ligated cytochrome P411 enzymes that catalyze the first primary amination of C(sp³)-H bonds with excellent selectivity, affording a broad scope of enantioenriched primary amines. Chapter III demonstrates that these new-to-nature nitrene transferases were engineered to aminate and amidate unactivated, unbiased C(sp³)-H bonds with unprecedented selectivity. In Chapter IV, engineered protoglobins are shown to utilize hydroxylamine (NH₂OH) for nitrene transfer reactions, including benzylic C-H primary amination and styrene aminohydroxylation. Overall, these new-to-nature reactions can be considered the nitrogen analogs to the C-H oxidation chemistry performed by monooxygenases and peroxygenases. By offering a direct path from saturated precursors, these enzymes present a new biochemical logic for accessing nitrogen-containing compounds. Finally, this work hints at the possible future discovery of natural enzymes that use hydroxylamine precursors for amination chemistry.

English

ISBN: 9798381032376Subjects--Topical Terms:

523812
Pharmaceutical sciences.

Engineering Heme Proteins for C(Sp³)-H Primary Amination /
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520 $a Primary amine is one of the most prevalent moieties in synthetic intermediates and pharmaceutical compounds. The preparation of aliphatic primary amines via C−H functionalization would provide direct access to the nitrogen-containing compounds from hydrocarbon substrates. While the enzymatic oxyfunctionalization of C-H bonds is well established, the analogous strategy for nitrogen incorporation is unknown in Nature. Likewise, a synthetic method for selective primary amination of aliphatic C-H bonds remains elusive. Combining chemical intuition and inspiration from Nature, chemists and protein engineers have created new heme-containing enzymes for the C(sp³)-H primary amination via directed evolution. This thesis describes some of the efforts in the continued pursuit of these new-to-nature reactions. Chapter I discusses directed evolution in the context of biocatalysis, the strategies for introducing new-to-nature chemistry in enzymes, the discovery of nitrene transferases from the cytochrome P450 monooxygenase, and finally, the development of C(sp³)-H primary aminases. Chapter II details the discovery and engineering of serine-ligated cytochrome P411 enzymes that catalyze the first primary amination of C(sp³)-H bonds with excellent selectivity, affording a broad scope of enantioenriched primary amines. Chapter III demonstrates that these new-to-nature nitrene transferases were engineered to aminate and amidate unactivated, unbiased C(sp³)-H bonds with unprecedented selectivity. In Chapter IV, engineered protoglobins are shown to utilize hydroxylamine (NH₂OH) for nitrene transfer reactions, including benzylic C-H primary amination and styrene aminohydroxylation. Overall, these new-to-nature reactions can be considered the nitrogen analogs to the C-H oxidation chemistry performed by monooxygenases and peroxygenases. By offering a direct path from saturated precursors, these enzymes present a new biochemical logic for accessing nitrogen-containing compounds. Finally, this work hints at the possible future discovery of natural enzymes that use hydroxylamine precursors for amination chemistry.
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