Total synthesis of marinomycins A-C and of their monomeric counterparts monomarinomycin A and iso-monomarinomycin A

K. C. Nicolaou, Andrea L. Nold, Robert R. Milburn, Corinna S. Schindler, Kevin P. Cole, Junichiro Yamaguchi

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Marinomycins A-C (1-3), and their monomeric analogues monomarinomycin A (m-1) and iso-monomarinomycin A (m-2), were synthesized by a convergent strategy from key building blocks ketophosphonate 5, aldehyde 6, and dienyl bromide carboxylic acid 7. The first attempt to construct marinomycin A [1, convertible to marinomycins B (2) and C (3) by light] by direct Suzuki-type dimerization/ cyclization of boronic acid dienyl bromide 4 led to premature ring closure to afford, after global desilylation, monomarinomycin A (m-1) and iso-monomarinomycin A (m-2) in good yield and only small amounts (≤2%) of the desired product. A subsequent stepwise approach based on Suzuki-type couplings improved considerably the overall yield of marinomycin A (1), and hence of marinomycins B (2) and C (3). Alternative direct dimerization approaches based on the Stille and Heck coupling reactions also led to monomarinomycins A (m-1 and m-2), but failed to deliver useful amounts of marinomycin A (1).

Original languageEnglish
Pages (from-to)1760-1768
Number of pages9
JournalJournal of the American Chemical Society
Volume129
Issue number6
DOIs
Publication statusPublished - 2007 Feb 14
Externally publishedYes

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Dimerization
Cyclization
Aldehydes
Bromides
Carboxylic acids
Boronic Acids
Acids
Carboxylic Acids
Light
marinomycin A
marinomycin C
marinomycin B

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Total synthesis of marinomycins A-C and of their monomeric counterparts monomarinomycin A and iso-monomarinomycin A. / Nicolaou, K. C.; Nold, Andrea L.; Milburn, Robert R.; Schindler, Corinna S.; Cole, Kevin P.; Yamaguchi, Junichiro.

In: Journal of the American Chemical Society, Vol. 129, No. 6, 14.02.2007, p. 1760-1768.

Research output: Contribution to journalArticle

Nicolaou, K. C. ; Nold, Andrea L. ; Milburn, Robert R. ; Schindler, Corinna S. ; Cole, Kevin P. ; Yamaguchi, Junichiro. / Total synthesis of marinomycins A-C and of their monomeric counterparts monomarinomycin A and iso-monomarinomycin A. In: Journal of the American Chemical Society. 2007 ; Vol. 129, No. 6. pp. 1760-1768.
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