Total Synthesis of Marine Macrolide Mangrolide D

Total synthesis of mangrolide D is described in this dissertation. A highly convergent 16-step total synthesis has been accomplished, featuring three robust and interchangeable bond forming reactions: Suzuki cross coupling, ring closing metathesis and α-selective glycosylation reaction. The convergent assembly of chemical building blocks enabled the quick access to mangrolide D and served as a potential pathway to other glycosylated macrolide compounds. Meanwhile, we developed a concise synthetic route to access the rare and unique sugar moiety in mangrolide D, 4-epi-vancosamine, which had no reported synthetic protocols before. The synthesis of sugar moiety featured an iron-mediated hydroazidation of the exo-cyclic double bond that regio- and stereoselectively generated the azido sugar. Moreover, the structure of mangrolide D and the absolute configuration of attached sugar moiety were fully confirmed through this total synthesis. Although mangrolide D did not register the antibiotic activity, this convergent and efficient synthetic route still facilitates future synthesis of mangrolide analogues as well as other structurally similar macrolides, like fidaxomicin and its analogues, for the purpose of new drug discovery.

Author dc:creator

• Gong, Junyu

Contributors dc:contributor

• Ready, Joseph M.
• De Brabander, Jef K.
• Tambar, Uttam
• Chen, Chuo

• Anti-Bacterial Agents
• Macrolides
• Polyenes

Language dc:language

en

Identifier

1345260468

OAI identifier oai:identifier

oai:utswmed-ir.tdl.org:2152.5/9978