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. 2006 Dec 21;8(26):6087-90.
doi: 10.1021/ol062595u.

De novo formal synthesis of (-)-apicularen A via an iterative asymmetric hydration sequence

Miaosheng Li  1 , George A O'Doherty
Affiliations

De novo formal synthesis of (-)-apicularen A via an iterative asymmetric hydration sequence

Miaosheng Li et al. Org Lett. .

Abstract

[Structure: see text] A de novo approach to the formal total synthesis of the macrolide natural product (-)-apicularen A has been achieved in 18 steps from achiral starting materials. Both the absolute and relative stereochemistries of apicularen A were introduced by a Sharpless asymmetric dihydroxylation, a pi-allyl-palladium catalyzed reduction, a stereoselective reduction, and a base-promoted transannulation to install the C-9 stereocenter.

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Figures

Scheme 1
Scheme 1
Biological Activity of (-)-Apicularen A and B
Scheme 2
Scheme 2
Retrosynthesis of (-)-Apicularen A (1).
Scheme 3
Scheme 3
Synthesis of Dienoate 9 and Its Bis-hydration.
Scheme 4
Scheme 4
Synthesis of Intermediate 7 via Stereoselective Reduction or Asymmetric Allylation.
Scheme 5
Scheme 5
Synthesis of Salicylate 23 via Cross-Metathesis Reaction.
Scheme 6
Scheme 6
Completion of Formal Synthesis of (-)-Apicularen A.
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References

    1. Kunze B, Jansen R, Sasse F, Höfle G, Reichenbach H. J. Antibiot. 1998;51:1075–1080. - PubMed
    2. Jansen R, Kunze B, Reichenbach H, Höfle G. Eur. J. Org. Chem. 2000:913–919.
    1. Boyd MR, Farina C, Belfiore P, Gagliardi S, Kim JW, Hayakawa Y, Beutler JA, McKee TC, Bowman BJ, Bowman EJ. J. Pharmacol. Exp. Ther. 2001;297:114–120. - PubMed
    2. Huss M, Sasse F, Kunze B, Jansen R, Steinmetz H, Ingenhorst G, Zeeck A, Wieczorek H. BMC Biochem. 2005;6:13. - PMC - PubMed
    1. Bhattacharjee A, Seguil OR, De Brabander JK. Tetrahedron Lett. 2001;42:1217–1220.
    2. Nicolaou KC, Kim DW, Baati R. Angew. Chem. Int. Ed. 2002;41:3701–3704. - PubMed
    3. Su Q, Panek JS. J. Am. Chem. Soc. 2004;126:2425–2430. - PubMed
    4. Petri AF, Bayer A, Maier ME. Angew. Chem. Int. Ed. 2004;43:5821–5823. - PubMed
    1. Lewis A, Stefanuti I, Swain SA, Smith SA, Taylor RJK. Tetrahedron Lett. 2001;42:5549–5552.
    2. Lewis A, Stefanuti I, Swain SA, Smith SA, Taylor RJK. Org. Biomol. Chem. 2003;1:104–116. - PubMed
    3. Graetz BR, Rychnovsky SD. Org. Lett. 2003;5:3357–3360. - PubMed
    4. Kühnert S, Maier ME. Org. Lett. 2002;4:643–646. - PubMed
    5. Hilli F, White JM, Rizzacasa MA. Tetrahedron Lett. 2002;43:8507–8510.
    6. Hilli F, White JM, Rizzacasa MA. Org. Lett. 2004;6:1289–1292. - PubMed

    1. While Maier’s endgame seemed ideal for our purpose, his use of a stochiometric amount (CF3CO2)2Hg to set the trans-annular ether bridge in macrolide 3 (see ref 3d) was viewed as needing to be replaced with an environmentally more benign yet equally stereoselective process.

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