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. 2024 Dec 18;30(71):e202403408.
doi: 10.1002/chem.202403408. Epub 2024 Nov 12.

Total Synthesis of Tosyl-Samroiyotmycin A and Its Biological Profiling

Benedikt Kolb  1 , Fabian Schmid  1 , Jessica Weng  1 , Luca Altevogt  1 , Ruben Pereira Rebelo  1 , Bianca Wank  1 , Angelika Baro  1 , Anna Zens  1 , Aditya Shekhar  2 , Ursula Bilitewski  2 , Sibylle Sax  3 , Sergio Wittlin  3 , Dale Taylor  4 , Rudolf Müller  5 , Sabine Laschat  1
Affiliations

Total Synthesis of Tosyl-Samroiyotmycin A and Its Biological Profiling

Benedikt Kolb et al. Chemistry. .

Abstract

A total synthesis of the enantiopure syn,syn-tosyl-samroiyotmycin A, a C2-symmetric 20-membered antimalarial macrodiolide with syn,syn-configuration of the 8,24-dihydroxy-9,25-dimethyl units and it's enantiopure anti,anti-derivative is described. The synthesis was accomplished utilizing a linear approach in 7 steps and 3 % overall yield via a sequence of diastereoselective methylation of SuperQuat oxazolidinone auxiliary, cross metathesis and Yamaguchi macrolactonization of fully functionalized seco-acids. By a similar approach we gained access to several samroiyotmycin analogues and precursors. Antimalarial activity was tested on multi-resistant (K1) and sensitive (Nf54) P. falciparum strains providing insight into structure activity relationships. Both tosyl-oxazol unit as well as the syn-configuration of the two contiguous stereogenic centers turned out to be beneficial for antiplasmodial activity. For instance, syn,syn-tosyl-samroiyotmycin A showed 3.4 times higher activities than the "tosyl-free" natural product.

Keywords: Antimalarial activity; Biological profiling; Macrocycles; Macrodiolide; Natural products.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Some prominent macrodiolides 1–4.
Scheme 1
Scheme 1
Pathways to samroiyotmycin A syn,syn–4 a and its tosylated analogue syn,syn–Ts–4 a.
Scheme 2
Scheme 2
Synthetic routes to seco‐acids syn‐8 and anti‐8.
Scheme 3
Scheme 3
Synthesis of samroiyotmycin derivatives and heteroaryl analogues (for further details see Scheme S4, S5).
See this image and copyright information in PMC

References

    1. Singh Y. J., Yarrapothu G. R., Vemula R., RSC Adv. 2013, 3, 55–58.
    1. Zhang S., Menche D., Zahler S., Vollmar A. M., Liebl J., Förster F., Pharm. - Int. J. Pharm. Sci. 2015, 70, 610–615. - PubMed
    1. Gronewold T. M. A., Sasse F., Lünsdorf H., Reichenbach H., Cell Tissue Res. 1999, 295, 121–129. - PubMed
    1. Huang W., Wu Q., Zhang M., Kong Y., Cao P., Zheng W., Xu J., Ye M., Cancer Lett. 2015, 356, 862–871. - PubMed
    1. Huang W., Ye M., Zhang L., Wu Q., Zhang M., Xu J., Zheng W., Mol. Cancer 2014, 13, 150. - PMC - PubMed

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