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
. 2010 Apr 12;16(14):4328-36.
doi: 10.1002/chem.200903500.

Total synthesis and configurational assignment of chondramide A

Anke Schmauder  1 , L David Sibley, Martin E Maier
Affiliations

Total synthesis and configurational assignment of chondramide A

Anke Schmauder et al. Chemistry. .

Abstract

The first total synthesis of the cyclodepsipeptide chondramide A (2 b) is described. This depsipeptide is composed of four subunits, namely L-alanine, N-Me-D-tryptophan, 3-amino-2-methoxy-propionic acid (beta-tyrosine derivative), and a 7-hydroxy-alkenoic acid. While the configuration of the stereogenic centers in the 7-hydroxy-alkenoic acid were known, the configuration of the tyrosine derivative required clarification and turned out to be (2S,3R) or (2L,3L), respectively. The synthesis of the 3-amino-2-methoxy-3-arylpropanoic ester 20 b relied on an asymmetric dihydroxylation yielding diol ent-15 a followed by a regioselective Mitsunobu substitution leading to 3-azido-2-hydroxypropanoate 18 b. We could also show that the ester bond in the seco compound 26 b can be fashioned by a Mitsunobu esterification by using hydroxy ester (7S)-7 and the tripeptide acid 25 b. This synthesis should allow for the preparation of various analogues.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of jasplakinolide and the chondramides. The atom numbering follows the suggestions from the isolation papers.
Figure 2
Figure 2
Key fragments for the synthesis of chondramide A diastereomers.
Scheme 1
Scheme 1
Summary of the synthesis of hydroxy ester 7.
Scheme 2
Scheme 2
Synthesis of the (2D,3L)-diastereomer 20a via the anti-acetoxy bromo ester 16a.
Scheme 3
Scheme 3
Synthesis of the (2D,3L)-3-amino-2-methoxy acid 20a via an aminohydroxylation reaction.
Scheme 4
Scheme 4
Synthesis of diastereomer 2a which does not correspond to chondramide A from the three building blocks 6, 20a, and 7.
Scheme 5
Scheme 5
Attempted synthesis of amino ester 20b and its incorporation in the cyclodepsipeptide. The obtained product 2c did not correspond to chondramide A.
Scheme 6
Scheme 6
Postulated formation of ent-16a from diol 15b via isomerization of cyclic oxonium ion B to D.
Scheme 7
Scheme 7
Independent synthesis of 3-amino-2-methoxy-tyrosine derivative ent-20b by aminhydroxylation.
Scheme 8
Scheme 8
Synthesis of the anti-diastereomer (2L,3L) 20b via dihydroxylation and substitution of the benzylic hydroxyl group by azide.
Scheme 9
Scheme 9
Synthesis of chondramide A (2b).
See this image and copyright information in PMC

References

    1. Disanza A, Steffen A, Hertzog M, Frittoli E, Rottner K, Scita G. Cell Mol Life Sci. 2005;62:955–970. - PMC - PubMed
    1. Kustermans G, Piette J, Legrand-Poels S. Biochem Pharmacol. 2008;76:1310–1322. - PubMed
    2. Binder M, Tamm C. Angew Chem. 1973;85:369–381. - PubMed
    3. Angew Chem Int Ed Engl. 1973;12:370–380. - PubMed
    1. Wieland T. Naturwissenschaften. 1987;74:367–373. - PubMed
    2. Cooper JA. J Cell Biol. 1987;105:1473–1478. - PMC - PubMed

    1. For recent reviews, see: Myles DC. Ann Rep Med Chem. 2002;37:125–132.Altmann KH, Gertsch J. Nat Prod Rep. 2007;24:327–357.Altmann KH, Pfeiffer B, Arseniyadis S, Pratt BA, Nicolaou KC. Chem Med Chem. 2007;2:396–423.Nicolaou KC, Chen JS, Dalby SM. Bioorg Med Chem. 2009;17:2290–2303.

    1. For review about cyclodepsipeptides, see: Hamada Y, Shioiri T. Chem Rev. 2005;105:4441–4482.

Publication types

LinkOut - more resources