Total synthesis and immunosuppressive activity of (-)-pateamine A and related compounds: Implementation of a β-lactam-based macrocyclization

Daniel Romo, Robert M. Rzasa, Helene A. Shea, Kaapjoo Park, Joseph M. Langenhan, Luo Sun, Alexander Akhiezer, Jun Liu

Research output: Contribution to journalArticle

Abstract

The asymmetric synthesis of the potent immunosuppressive agent (-)- pateamine A isolated from the marine sponge Mycale sp. is described. A key strategy employed in the synthesis was a β-lactam-based macrocyclization to form the 19-membered dilactone macrolide. The synthesis confirms the relative and absolute stereochemistry as 3R,5S, 10S,24S and sets the stage for studies into the mechanism of action of pateamine A. Other studies and findings made in the course of the synthesis and described herein include the following: (1) a Stille coupling can be competitive with π-allyl formation, (2) SmI2 effects a mild N-O cleavage of N-benzyloxy-β-lactams, (3) the synthesis of a pateamine A-dexamethasone hybrid molecule for use in a yeast three-hybrid assay was accomplished, and (4) IC50 values were determined for synthetic and natural pateamine A and related compounds in the interleukin 2 reporter gene assay.

Original languageEnglish (US)
Pages (from-to)12237-12254
Number of pages18
JournalJournal of the American Chemical Society
Volume120
Issue number47
DOIs
StatePublished - Dec 2 1998
Externally publishedYes

Fingerprint

Lactams
Immunosuppressive Agents
Assays
Two-Hybrid System Techniques
Macrolides
Porifera
Reporter Genes
Stereochemistry
Dexamethasone
Inhibitory Concentration 50
Interleukin-2
Yeast
Genes
pateamine A
Molecules

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Total synthesis and immunosuppressive activity of (-)-pateamine A and related compounds : Implementation of a β-lactam-based macrocyclization. / Romo, Daniel; Rzasa, Robert M.; Shea, Helene A.; Park, Kaapjoo; Langenhan, Joseph M.; Sun, Luo; Akhiezer, Alexander; Liu, Jun.

In: Journal of the American Chemical Society, Vol. 120, No. 47, 02.12.1998, p. 12237-12254.

Research output: Contribution to journalArticle

Romo, Daniel ; Rzasa, Robert M. ; Shea, Helene A. ; Park, Kaapjoo ; Langenhan, Joseph M. ; Sun, Luo ; Akhiezer, Alexander ; Liu, Jun. / Total synthesis and immunosuppressive activity of (-)-pateamine A and related compounds : Implementation of a β-lactam-based macrocyclization. In: Journal of the American Chemical Society. 1998 ; Vol. 120, No. 47. pp. 12237-12254.
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AU - Akhiezer, Alexander

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