Total synthesis of (-)-pulvomycin
Final Report Abstract
The pulvomycins are labile polyketide natural products containing three 1,3,5- triene unit, one sugar fragment (labilose) and a 22-membered macrolactone ring. Pulvomycin A displays a known and well understood antibiotic activity while pulvomycin D displays a cytotoxicity that has so far been studied only cursorily. Both compounds differ only in the oxidation state at carbon atom C13 (alcohol vs. ketone). The synthesis of a protected precursor to both pulvomycins succeeded by an assembly of three building blocks which contained the skeletal carbon atoms C1- C7, C8-C23, and C24-C40 (22 synthetic steps in the longest sequence with an average yield of 76% per step). Key reactions of the synthesis included a diastereoselective aldol reaction, a site-selective esterification, and an intra- molecular Heck reaction. The removal of six silyl protecing groups in the protected precursor and the liberation of the masked triene by a Peterson elimination required a two-step deprotection protocol. The alcohol at C13 was concomitantly oxidized completing the total synthesis of pulvomycin D, the first pulvomycin ever prepared synthetically.
Publications
- ‘Total synthesis of (−)-Bretonin B: Access to the (E,Z,E)-triene core by a latestage Peterson elimination of a convergently assembled silyl ether‘ Chem. Commun. 2012, 48, 11629-11631
T. Neubauer, C. Kammerer-Pentier, T. Bach
(See online at https://doi.org/10.1039/C2CC36604E) - ‘Enantioselective synthesis of the C24-C40 fragment of (−)-pulvomycin‘ Chem. Commun. 2014, 50, 4901-4903
S. Börding, T. Bach
(See online at https://doi.org/10.1039/c0xx00000x) - ‘Studies towards the Synthesis of (−)-Pulvomycin: Construction of the C12-C40 Segment by a Stereoselective Aldol Reaction‘ Synthesis 2021, 54, 4246-4262
S. Wienhold, L. Fritz, T. Judt, S. Hackl, T. Neubauer, B. Sauerer, T. Bach
(See online at https://doi.org/10.1055/a-1464-2576) - ‘Total Synthesis of Pulvomycin D‘ Chem. Eur. J. 2022, 28
L. Fritz, S. Wienhold, S. Hackl, T. Bach
(See online at https://doi.org/10.1002/chem.202104064)
