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Semisynthesis of an Anticancer DPAGT1 Inhibitor from a Muraymycin Biosynthetic Intermediate

Mitachi, Katsuhiko and Kurosu, Shou M. and Eslamimehr, Shakiba and Lemieux, Maddie R. and Ishizaki, Yoshimasa and Clemons, William M., Jr. and Kurosu, Michio (2019) Semisynthesis of an Anticancer DPAGT1 Inhibitor from a Muraymycin Biosynthetic Intermediate. Organic Letters, 21 (4). pp. 876-879. ISSN 1523-7060. PMCID PMC6447083. http://resolver.caltech.edu/CaltechAUTHORS:20190130-162009556

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Abstract

We have explored a method to convert a muraymycin biosynthetic intermediate 3 to an anticancer drug lead 2 for in vivo and thorough preclinical studies. Cu(OAc)_2 forms a stable complex with the amide 4 and prevents electrophilic reactions at the 2-((3-aminopropyl)amino)acetamide moiety. Under the present conditions, the desired 5″-primary amine was selectively protected with (Boc)_2O to yield 6. The intermediate 6 was converted to 2 in two steps with 90% yield.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/acs.orglett.8b03716DOIArticle
https://pubs.acs.org/doi/suppl/10.1021/acs.orglett.8b03716PublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447083PubMed CentralArticle
ORCID:
AuthorORCID
Clemons, William M., Jr.0000-0002-0021-889X
Kurosu, Michio0000-0003-0092-0619
Additional Information:© 2019 American Chemical Society. Received: November 20, 2018; Published: January 30, 2019. We thank the National Institutes of Health (Grant No. GM114611). M.K. also thanks the University of Tennessee Health Science Center for generous financial support (UTHSC College of Pharmacy, CORNET, and UTRF awards). NMR data were obtained on instruments supported by the NIH Shared Instrumentation Grant. Streptomyces sp. NRRL 30471 was acquired from USDA (NRRL Culture Collection). The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHGM114611
University of TennesseeUNSPECIFIED
PubMed Central ID:PMC6447083
Record Number:CaltechAUTHORS:20190130-162009556
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190130-162009556
Official Citation:Semisynthesis of an Anticancer DPAGT1 Inhibitor from a Muraymycin Biosynthetic Intermediate. Katsuhiko Mitachi, Shou M. Kurosu, Shakiba Eslamimehr, Maddie R. Lemieux, Yoshimasa Ishizaki, William M. Clemons, Jr., and Michio Kurosu. Organic Letters 2019 21 (4), 876-879. DOI: 10.1021/acs.orglett.8b03716
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:92532
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:31 Jan 2019 23:19
Last Modified:05 Apr 2019 17:00

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