The synthesis of o-benzoyl hydroxamates and secondary amines from 0-benzoyloxyamines and the total synthesis of acinetoferrin

Abstract

A novel siderophore, acinetoferrin, isolated in 1994 from Acinetobacter haemolyticus is currently under investigation in our laboratory. The total synthesis of this unusual iron chelator is described. A new synthetic method was developed to access the a, /3-unsaturated hydroxamic acid structural element of this siderophore. To this end, a biphasic method was used to convert a primary amine into a benzoyloxyamine. The 0-(benzoyl)hydroxylamine intermediate was subsequently acylated to form the desired 0- benzoyl hydroxamate. In terms of acinetoferrin synthesis, the key transformation involved the tandem oxidation and acylation of the N3-amino group of N1-BOC propane diamine prior to coupling with the external carboxyls of citric acid. In general the intermediate benzoyloxyarnines were expected to have diverse chemistry. Therefore, we were interested in the initial oxidation step to both access acinetoferrin and to gain entry into a new class of reactive intermediates, the benzoyloxyarnines. Model studies with phenethylarnine were used to optimize the selective oxidation of a primary amine to a benzoyloxyamine. Early studies using benzoyl peroxide as the oxidant identified two competing pathways: N-oxidation and N-acylation. A biphasic method was found to increase both the selectivity and yield of the N-oxidized product at the expense of the benzamide byproduct. A careful tudy of the benzoyl peroxide-mediated process revealed a dramatic dependence on the pH, the molar ratio of the amine and the peroxide used. The optimal condition utilized a biphasic system, which included equal volumes of a pH 10.5 aqueous buffer and CH2Cl2 with I mL methylene chloride per 0.1

mmol of phenethylamine, 2 equivalents of benzoyl peroxide and 1 equivalent of phenylethylamine at room temperature. These conditions were also found suitable for the oxidation of secondary amines to N,N-dialkyJ-(benzoyloxy)amines. As a further extension of the amine oxidation chemistry, we discovered that trialkylboranes reacted with benzoyloxyamines to give functionally substituted secondary amines. In short, these studies have demonstrated the utility of benzoyloxyamines in both the synthesis of a, P-unsaturated hydroxamic acids and secondary amines.

Notes

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Graduation Date

1997

Semester

Spring

Degree

Master of Science (M.S.)

College

College of Arts and Sciences

Format

PDF

Pages

86

Language

English

Length of Campus-only Access

None

Access Status

Masters Thesis (Open Access)

Identifier

DP0028695

Subjects

Arts and Sciences -- Dissertations, Academic; Dissertations, Academic -- Arts and Sciences

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