Asset Details
Do you wish to reserve the book?
Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1
Do you wish to request the book?
Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Design and 22-step synthesis of highly potent D-ring modified and linker-equipped analogs of spongistatin 1
2018
Overview
Spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody–drug conjugates and other targeted delivery approaches. Unfortunately, it is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive. As a result, the design and synthesis of more acid-stable and linker functional group-equipped analogs that retain the low picomolar potency of the parent natural product requires more efficient and step-economical synthetic access. Using uniquely enabling direct complex fragment coupling crotyl- and alkallylsilylation reactions, we report a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is characterized by GI
50
values in the low picomolar range, and a proof-of-concept result that the C(15) acetate may be replaced with linker functional group-bearing esters with only minimal reductions in potency.
Step-economical and efficient syntheses of Spongistatin 1 analogs are desirable for the development of potent anti-proliferative agents. Here, the authors report a 22-step synthesis of a D-ring modified Spongistatin 1 analog with retained picomolar potency among a group of C(15) ester derivatives.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
