Synthesis of Altromycin and Kidamycin Aglycones from a Common Intermediate & Studies towards the Total Synthesis of Kidamycin Open Access

Abstract

Chapter1. Synthesis of Altromycin and Kidamycin Aglycones from a Common Intermediate

The anthrapyran structures 3 and 4, respectively corresponding to the aglycones of antitumor antibiotic natural products altromycin and kidamycin, have been efficiently synthesized from a common intermediate 2. A series of Claisen condensations and aromatizations from hydroxyl glutarate 1 affords the anthracene section of 2, and an intramolecular Friedel-Crafts reaction annulates the pyrone ring. The functional groups of 2 can be manipulated for enantioselective introduction of the epoxide side-chain of altromycin aglycone 3, as well as synthesis of the kidamycin aglycone 2.

Chapter 2. Studies towards the Total Synthesis of Kidamycin

Enantiomerically enriched angolosamine synthon 4 and vancosamine synthon 5, corresponding to the carbohydrate moieties of kidamycin, have been identified as good glycosyl donors in kidamycin glycosylation studies, and synthesized by applying tungsten-catalyzed cycloisomerization of alkynols into glycals. Glycosylation studies with 4 and 5 have been directed at identification of a good glycosyl acceptor 2 to target the total synthesis of kidamycin. Glycosyl acceptor 2 has been efficiently synthesized via double Friedel-Crafts cyclization of 1. Sequential glycosylations of 2 with 4 and 5 provide an advanced intermediate 7 possessing the full carbon skeleton of kidamycin

Table of Contents

Chapter1. Synthesis of Altromycin and Kidamycin Aglycones from a Common Intermediate 1.1 Introduction and background 1.2 Results and discussion 1.2.1 Overall description of the results 1.2.2 Synthesis of an anthrapyran intermediate 1.2.3 Completion of altromycin aglycone synthesis 1.2.4 Completion of kidamycin aglycone synthesis 1.3 Conclusions 1.4 Experimental information 1.5 Citations Chapter 2. Studies towards the Total Synthesis of Kidamycin 2.1 Background and strategy 2.2 Results and discussion 2.2.1 Initial glycosylation studies 2.2.1.1 Angolosamine glycosyl donor 2.2.1.2 Vancosamine glycosyl donor 2.2.1.3 Glycosylations with vancosamine glycosyl donor (1) Glycosylations of 1-naphthol (2) Glycosylations of naphthalene-type synthetic intermediate (3) Glycosylation of anthracene-type synthetic intermediate 2.2.1.4 Glycosylations with angolosamine glycosyl donor 2.2.1.5 Strategy modification 2.2.2 Modified strategy to the total synthesis 2.2.2.1 Synthesis of modified aglycone as good glycosyl acceptor (1) Initial strategy to synthesize the modified aglycone (2) Initial attempt to synthesize the modified aglycone (3) Final success in synthesis of the modified aglycone 2.2.2.2 Glycosylations with modified aglycone intermediates 2.3 Conclusions 2.4 Experimental information 2.5 Citations

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School	Laney Graduate School
Department	Chemistry
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Chemistry, Organic
Keyword	kidamycin and altromycin aglycones natural antiobiotics
Committee Chair / Thesis Advisor	McDonald, Frank, Emory University
Committee Members	Liotta, Dennis C, Emory University Padwa, Albert, Emory University

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