Synthesis of Indole Alkaloids and Development of New Methodology

Research output: ThesisDoctoral Thesis (compilation)

Standard

Synthesis of Indole Alkaloids and Development of New Methodology. / Hoang, Anita.

Lund : Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering, 2019. 161 p.

Research output: ThesisDoctoral Thesis (compilation)

Harvard

Hoang, A 2019, 'Synthesis of Indole Alkaloids and Development of New Methodology', Doctor, Department of Chemistry, Lund.

APA

Hoang, A. (2019). Synthesis of Indole Alkaloids and Development of New Methodology. Lund: Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering.

CBE

Hoang A. 2019. Synthesis of Indole Alkaloids and Development of New Methodology. Lund: Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering. 161 p.

MLA

Hoang, Anita Synthesis of Indole Alkaloids and Development of New Methodology Lund: Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering. 2019.

Vancouver

Hoang A. Synthesis of Indole Alkaloids and Development of New Methodology. Lund: Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering, 2019. 161 p.

Author

Hoang, Anita. / Synthesis of Indole Alkaloids and Development of New Methodology. Lund : Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering, 2019. 161 p.

RIS

TY - THES

T1 - Synthesis of Indole Alkaloids and Development of New Methodology

AU - Hoang, Anita

N1 - Defence details Date: 2019-04-12 Time: 09:00 Place: Sal B, Kemicentrum, Naturvetarvägen 14, Lund External reviewer(s) Name: Poulsen, Thomas Title: Ass. Professor Affiliation: Aarhus University, Denmark ---

PY - 2019/3

Y1 - 2019/3

N2 - This thesis describes our efforts towards the total synthesis of natural products and the development of a newmethodology to afford a synthetically important scaffold.Chapter 2 outlines our efforts towards the total synthesis of a marine natural product, perophoramidine as wellas our completed synthesis of dehaloperophoramidine. The focus of the studies was to develop an efficient andconcise strategy to afford the natural products. We aimed at utilising the inherent structure and symmetry of thenatural product to encourage domino processes and gain access to the key features. The vicinal quaternarystereocenters were installed by employing Overman’s diastereoselective dialkylation protocol. Two new dominoprocesses were discovered. The first domino process led to the formation of the ortho-amide and carefulinvestigation of its reactivity led to the discovery of the second domino process which ultimately delivereddehaloperophoramidine. The synthesis was completed in eight steps starting from isoindigo.Chapter 3 describes our efforts towards the total synthesis of strictamine. The key features of strictamine thatneed to be addressed when pursuing the synthesis are: (i) the quaternary stereocenter, (ii) the centralcyclohexane moiety (D ring) with four stereocenters, and (iii) the cage-like methanoquinolizidine core. We aimedat accessing these key features through intramolecular Heck reaction to access the central D ring with parts ofthe substitution pattern already present and the quaternary stereocenter. For the methanoquinolizidine core, weplanned to adopt our previously described domino carbopalladation/carbonylation protocol. The synthesis is inan advanced state with two additional functionalisation left in order to access the target compound. Described inthis chapter is our effort to access the core structure of strictamine with all the rings installed.The third part of this thesis deals with the development of a new methodology to access indoline scaffolds thatfeature an all-carbon quaternary stereocenter. We were able to synthesise allyl anilines through the regio- andstereoselective ring-opening of vinyl aziridines with 2-iodoaniline. The final indoline scaffold was furnished byintramolecular Heck reaction with concomitant formation of the quaternary stereocenter.

AB - This thesis describes our efforts towards the total synthesis of natural products and the development of a newmethodology to afford a synthetically important scaffold.Chapter 2 outlines our efforts towards the total synthesis of a marine natural product, perophoramidine as wellas our completed synthesis of dehaloperophoramidine. The focus of the studies was to develop an efficient andconcise strategy to afford the natural products. We aimed at utilising the inherent structure and symmetry of thenatural product to encourage domino processes and gain access to the key features. The vicinal quaternarystereocenters were installed by employing Overman’s diastereoselective dialkylation protocol. Two new dominoprocesses were discovered. The first domino process led to the formation of the ortho-amide and carefulinvestigation of its reactivity led to the discovery of the second domino process which ultimately delivereddehaloperophoramidine. The synthesis was completed in eight steps starting from isoindigo.Chapter 3 describes our efforts towards the total synthesis of strictamine. The key features of strictamine thatneed to be addressed when pursuing the synthesis are: (i) the quaternary stereocenter, (ii) the centralcyclohexane moiety (D ring) with four stereocenters, and (iii) the cage-like methanoquinolizidine core. We aimedat accessing these key features through intramolecular Heck reaction to access the central D ring with parts ofthe substitution pattern already present and the quaternary stereocenter. For the methanoquinolizidine core, weplanned to adopt our previously described domino carbopalladation/carbonylation protocol. The synthesis is inan advanced state with two additional functionalisation left in order to access the target compound. Described inthis chapter is our effort to access the core structure of strictamine with all the rings installed.The third part of this thesis deals with the development of a new methodology to access indoline scaffolds thatfeature an all-carbon quaternary stereocenter. We were able to synthesise allyl anilines through the regio- andstereoselective ring-opening of vinyl aziridines with 2-iodoaniline. The final indoline scaffold was furnished byintramolecular Heck reaction with concomitant formation of the quaternary stereocenter.

KW - total synthesis

KW - indole alkaloids

KW - Domino reactions

KW - vicinal quaternary stereocenters

KW - quaternary stereocenter

KW - indoline synthesis

KW - communesin alkaloid

KW - perophoramidine

KW - dehaloperophoramidine

KW - akuammiline alkaloids

KW - strictamine

KW - intramolecular Heck reaction

KW - domino carbopalladation carbonylation

KW - indoline alkaloids

M3 - Doctoral Thesis (compilation)

SN - 978-91-7422-645-4

PB - Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering

CY - Lund

ER -