عنوان

Development of Non-natural Biocatalytic Methods for Asymmetric Radical Reactions

شماره

TL56132

زبان متن نوشتاري يا گفتاري و مانند آن

انگلیسی

عنوان اصلي

Development of Non-natural Biocatalytic Methods for Asymmetric Radical Reactions

نام عام مواد

[Thesis]

نام نخستين پديدآور

Sandoval, Braddock Alexander

نام ساير پديدآوران

Hyster, Todd K.

نام ناشر، پخش کننده و غيره

Princeton University

تاریخ نشرو بخش و غیره

2020

متن يادداشت

179 p.

جزئيات پايان نامه و نوع درجه آن

Ph.D.

کسي که مدرک را اعطا کرده

Princeton University

امتياز متن

2020

متن يادداشت

Biocatalysis has become an increasingly important tool for the efficient construction of complex organic molecules. Enzymes offer several advantages over traditional small-molecule catalysts including exquisite selectivities, high turnover numbers, and a powerful catalyst optimization strategy via protein engineering and directed-evolution. Consequently, numerous examples exist of engineered enzymes substituting traditional synthetic methods, thereby increasing the efficiency of chemical synthesis. Despite these exciting developments, it is also clear that there is still room for improvement, particularly in the realm of chemical reactivity, where biocatalysis is dwarfed by the sheer number of chemical reactions available using traditional synthetic approaches. For these reasons, there is a great interest and an enduring challenge of finding new reactions which can be performed using enzymes. The research described herein focuses on addressing long-standing challenges in asymmetric catalysis by using enzymes as a platform for the development of new reactivity. By developing new asymmetric reactions that are difficult to affect using traditional or biocatalytic methods, it is our lab's hope that the scope of synthetic organic chemistry will be expanded in a useful fashion. We were keenly interested in solving selectivity challenges in free radical mediated transformations, including terminating radical reactions via enantioselective hydrogen atom transfer (HAT). We hypothesized that flavin-dependent 'ene'-reductases (EREDs), an industrially relevant enzyme class, could serve as effective catalysts in this regard. While the role of flavoproteins in mediating single electron transfer (SET) has been explored in a biological context, direct single electron transfers from flavoenzymes to organic substrates are rare in nature, and had up until this point, never been studied within the framework of synthetic organic chemistry. In this dissertation I describe four distinct mechanisms by which radical chemistry can be initiated in an enzyme class which typically functions only through ionic mechanisms. This includes ground state SET, charge transfer complex photoexcitation-initiated SET, photoredox catalyst assisted SET, and direct photoinitiated SET. Each of these reaction manifolds allows for progressively more challenging reductions to occur, greatly broadening the scope of reactivity available this enzyme family.

اصطلاح موضوعی

Chemistry

اصطلاح موضوعی

Organic chemistry

مستند نام اشخاص تاييد نشده

Sandoval, Braddock Alexander

مستند نام اشخاص تاييد نشده

Hyster, Todd K.

مستند نام تنالگان تاييد نشده

Princeton University

نام الکترونيکي

فرمت انتشار

p

نوع ماده

[Thesis]

کد کاربرگه

276903

سطح دسترسي

a

تكميل شده

Y