Item Details

abstract

Hydroxamic acids are an important class of bioactive compounds with wide uses as anti-bacterial, or anti-inflammatory agents and a key component of many natural products, mainly siderophores (low-molecular-weight iron sequestering agents) in lower organisms. Hydroxamic acid based analogs may find potential therapeutic uses in the inhibition of siderophore biosynthesis. Our research targets to develop new synthetic methodology towards making cyclic hydroxamic acids in a stereoselective and regioselective fashion. Basic decomposition of Piloty's acid transforms cyclic ketones (mainly four and five membered) into ring-expanded cyclic hydroxamic acids in 20-69% yield (Scheme 1). Mechanistic study reveals this reaction involves a C-nitroso intermediate 98 (Scheme 47) in the course of the rearrangement, which can also be generated by a separate hydrolysis reaction of acyloxy nitroso intermediate 103 (Scheme 51) leading to the ring-expansion product in 75-80% yield.

subject

Cobactine and Mycobactic Acid

Cyclic Hydroxamic Acid

Hydrolysis of five membered ring acyloxy nitroso compound yields hydroxamic acid

Intermolecular nitroso-ene method to make linear

cyclic and long-chain hydroxamic acid

Intramolecular nitroso-ene method to make eight member ring hydroxamic acid

-NOH insertion into cyclic ketones in a regioselective and steroselctive fashion

contributor

Banerjee, Ranjan (author)

King, Stephen Bruce (committee chair)

Garg, Pradeep K (committee member)

Alexander, Rebecca W (committee member)

Colyer, Christa L (committee member)

Jones, Paul B (committee member)

date

2011-02-16T21:42:36Z (accessioned)

2012-12-14T09:30:08Z (available)

2010 (issued)

degree

Chemistry (discipline)

embargo

2012-12-14 (terms)

identifier

http://hdl.handle.net/10339/30428 (uri)

language

en (iso)

publisher

Wake Forest University

title

DEVELOPMENT OF SYNTHETIC METHODOLOGIES TOWARDS CYCLIC HYDROXAMIC ACID-BASED NATURAL PRODUCTS

type

Dissertation