Total synthesis of sarcodictyins A and B

K. C. Nicolaou, J. Y. Xu, S. Kim, J. Pfefferkorn, T. Ohshima, D. Vourloumis, Seijiro Hosokawa

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

The total synthesis of cytotoxic marine natural products possessing tubulin polymerization and microtubule stabilization properties, sarcodictyins A (7) and B (8), is described. Two related approaches to these target molecules have been developed, both utilizing (+)-carvone (9) as starting material. The first approach involves a stereoselective construction of acetylenic aldehyde 27 (Scheme 2) while the second approach proceeds through a more direct but less selective sequence to the similar intermediate 36 (Scheme 3). Both strategies involve ring closures of the acetylenic aldehyde precursors to 10-membered rings under basic conditions followed by elaboration and selective reduction of the acetylenic linkage to a cis double bond. This promotes bridging to form the required tricyclic skeleton of the sarcodictyins (27 → 37 → 38 → 39 4, Scheme 4 and 37 → 44 → 45 → 46 → 47 → 42, Scheme 5) and (36 → 48 → 45, Scheme 6). Installation of the (E)- N(6')-methylurocanic acid residue was achieved by esterification with mixed anhydride 52, while the C-3 ester moieties were installed by standard deprotection, oxidation, and esterification procedures.

Original languageEnglish
Pages (from-to)8661-8673
Number of pages13
JournalJournal of the American Chemical Society
Volume120
Issue number34
DOIs
Publication statusPublished - 1998 Sep 2
Externally publishedYes

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Esterification
Aldehydes
Anhydrides
Tubulin
Biological Products
Skeleton
Microtubules
Polymerization
Esters
Stabilization
Oxidation
Molecules
Acids
carvone
calcium ascorbate

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Nicolaou, K. C., Xu, J. Y., Kim, S., Pfefferkorn, J., Ohshima, T., Vourloumis, D., & Hosokawa, S. (1998). Total synthesis of sarcodictyins A and B. Journal of the American Chemical Society, 120(34), 8661-8673. https://doi.org/10.1021/ja981062g

Total synthesis of sarcodictyins A and B. / Nicolaou, K. C.; Xu, J. Y.; Kim, S.; Pfefferkorn, J.; Ohshima, T.; Vourloumis, D.; Hosokawa, Seijiro.

In: Journal of the American Chemical Society, Vol. 120, No. 34, 02.09.1998, p. 8661-8673.

Research output: Contribution to journalArticle

Nicolaou, KC, Xu, JY, Kim, S, Pfefferkorn, J, Ohshima, T, Vourloumis, D & Hosokawa, S 1998, 'Total synthesis of sarcodictyins A and B', Journal of the American Chemical Society, vol. 120, no. 34, pp. 8661-8673. https://doi.org/10.1021/ja981062g
Nicolaou KC, Xu JY, Kim S, Pfefferkorn J, Ohshima T, Vourloumis D et al. Total synthesis of sarcodictyins A and B. Journal of the American Chemical Society. 1998 Sep 2;120(34):8661-8673. https://doi.org/10.1021/ja981062g
Nicolaou, K. C. ; Xu, J. Y. ; Kim, S. ; Pfefferkorn, J. ; Ohshima, T. ; Vourloumis, D. ; Hosokawa, Seijiro. / Total synthesis of sarcodictyins A and B. In: Journal of the American Chemical Society. 1998 ; Vol. 120, No. 34. pp. 8661-8673.
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