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
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
STARS Citation
Wang, Queenie Xianghong, "The synthesis of o-benzoyl hydroxamates and secondary amines from 0-benzoyloxyamines and the total synthesis of acinetoferrin" (1997). Retrospective Theses and Dissertations. 2835.
https://stars.library.ucf.edu/rtd/2835