November 26th (Thursday) Graduate Seminar / Professor Yonghoon Kwon

Ring Closing Alkyne Metathesis in the Total Synthesis of Macrolides:

Disciformycins and Formosalides

The development of ring closing alkyne metathesis (RCAM) has rendered opportunities to access large/medium-sized macrolides. 1 Stereoselective reduction of the resulting alkyne following the RCAM can further provide Z - or E -alkenes. Beyond the selective formation of ( Z) - or ( E) -disubstituted alkenes, trisubstituted alkenes with well-defined stereochemistry can be prepared by a RCAM/ trans -selective hydrostannation sequence. This approach is complementary to ring closing alkene metathesis (RCM) since (stereoselective) formation of trisubstituted alkenes by RCM is problematic. Testing this method in the total synthesis of a complex natural product is desirable to broaden the generality of the strategy. First, disciformycins A and B isolated from cultures of Pyxidicoccus fallax 2 were chosen as our targets as they exhibit considerable antibacterial activity against Gram-positive bacteria. Also, we targeted 17-membered macrolide formosalides using the beneficial RCAM strategy. This presentation will describe details of unforeseen synthetic challenges and our endeavors to resolve these problems met along the way. 3,4

[1] F ü rstner, A. Angew. Chem. Int. Ed . 2013 , 52 , 2794 – 2819.

[2] Surup, F.; Viehrig, K.; Mohr, K. I.; Herrmann, J.; Jansen, R.; M ü lller, R. Angew. Chem. Int. Ed . 2014 , 53 , 13588 – 13591.

[3] Kwon, Y.; Schulthoff, S.; Dao, Q. M.; Wirtz, C.; F ü rstner, A. Chem. Eur. J . 2018 , 24 , 109 – 114.

[4] Schulthoff, S.; Hamilton, J. Y.; Heinrich, M.; Kwon, Y.; Wirtz, C.; F ü rstner, A. Angew. Chem. Int. Ed . ASAP doi.org/10.1002/anie.202011472