Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Jul 22;137(28):8900-3.
doi: 10.1021/jacs.5b05296. Epub 2015 Jul 13.

Direct Generation of Triketide Stereopolyads via Merged Redox-Construction Events: Total Synthesis of (+)-Zincophorin Methyl Ester

Affiliations

Direct Generation of Triketide Stereopolyads via Merged Redox-Construction Events: Total Synthesis of (+)-Zincophorin Methyl Ester

Zachary A Kasun et al. J Am Chem Soc. .

Abstract

(+)-Zincophorin methyl ester is prepared in 13 steps (longest linear sequence). A bidirectional redox-triggered double anti-crotylation of 2-methyl-1,3-propane diol directly assembles the triketide stereopolyad spanning C4-C12, significantly enhancing step economy and enabling construction of (+)-zincophorin methyl ester in nearly half the steps previously required.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(+)-Zincophorin and (+)-Zincophorin Methyl Ester and Summary of Prior Total Syntheses.a aFor graphical summaries of prior total syntheses, see Supporting Information. Longest Linear Sequence (LLS); Total Steps (TS).
Figure 2
Figure 2
Merged 1,2- and 1,3-Stereoinduction Model.a aR1 = C10-C3 of Fragment B, R2 = C15-C25 of Fragment A.
Scheme 1
Scheme 1
Retrosynthesis of (+)-Zincophorin Methyl Ester.
Scheme 2
Scheme 2
Synthesis of Fragment A via Direct anti-Crotylation of Allylic Alcohol 5.a aYields are of material isolated by silica gel chromatography. Enantiomeric excess was determined by chiral GLC. See Supporting Information for further experimental details.
Scheme 3
Scheme 3
Synthesis of Fragment B via Two-Directional Double anti-Crotylation of 2-Methyl-1,3-Propane Diol 1b.a aYields are of material isolated by silica gel chromatography. See Supporting Information for further experimental details.
Scheme 4
Scheme 4
Union of Fragment A and Fragment B and Total Synthesis of (+)-Zincophorin Methyl Ester.a aYields are of material isolated by silica gel chromatography. See Supporting Information for further experimental details.

Similar articles

Cited by

References

    1. Reviews: O’Hagan D. The Polyketide Metabolites. Ellis Horwood; Chichester: 1991. Rohr J. Angew Chem Int Ed. 2000;39:2847.Rimando AM, Baerson SR. ACS Symp Ser. 2007;955:282.Newman DJ, Cragg GM. J Nat Prod. 2007;70:461.Cragg GM, Grothaus PG, Newman DJ. Chem Rev. 2009;109:3012.

    1. Sait M, Hugenholtz P, Janssen PH. Environ Microbiol. 2002;4:654. and references cited therein. - PubMed
    1. Eribulin (halaven), a truncated analogue of the marine polyketide halichondrin B and FDA approved treatment for metastatic breast cancer, requires 65 steps for its preparation. Over half these steps are protecting group (PG) manipulations and redox reactions. Eribulin is 200 times more potent than taxol, which compensates for its relatively high manufacturing costs Yu MJ, Zheng W, Seletsky BM. Nat Prod Rep. 2013;30:1158.

    1. For selected reviews on enantioselective redox-triggered carbonyl addition from the alcohol oxidation level, see: Ketcham JM, Shin I, Montgomery TP, Krische MJ. Angew Chem Int Ed. 2014;53:9142.Dechert-Schmitt AMR, Schmitt DC, Gao X, Itoh T, Krische MJ. Nat Prod Rep. 2014;31:504.

    1. For a review on redox-economy, see: Burns NZ, Baran PS, Hoffmann RW. Angew Chem Int Ed. 2009;48:2854.

Publication types

MeSH terms

LinkOut - more resources