A versatile synthesis of "tafuramycin A": A potent anticancer and parasite attenuating agent
File version
Author(s)
Rose, Faith J
Healy, Peter C
von Itzstein, Mark
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
Size
File type(s)
Location
License
Abstract
An improved and versatile synthesis of tafuramycin A, a potent anticancer and parasite-attenuating agent, is reported. The three major improvements that optimized yield, simplified purification and allowed the synthesis of more versatile duocarmycin analogues are: a first-time reported regioselective bromination using DMAP as catalyst; the control of the aryl radical alkene cyclization step to prevent the dechlorination side reaction; and the design of a new protection/deprotection method to avoid furan double bond reduction during the classical O-benzyl deprotection in the final step. This alternative protection/deprotection strategy provides ready access to duocarmycin seco-analogues that carry labile functionalities under reducing reaction conditions. Tafuramycin A (3) was prepared in either 8 steps from intermediate 6 or 7 steps from intermediate 17 in 52% or 37% yield respectively. Our strategy provides a significant improvement on the original procedure (11% overall yield) and greater versatility for analogue development.
Journal Title
Organic & Biomolecular Chemistry
Conference Title
Book Title
Edition
Volume
12
Issue
24
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
Item Access Status
Note
Access the data
Related item(s)
Subject
Medicinal and biomolecular chemistry
Organic chemistry
Organic chemical synthesis