Stereoselective Total Synthesis of (−)‐Borrelidin

Abstract

A convergent synthesis of (−)‐borrelidin (1) is reported based on the retrosynthetic disconnections indicated in the picture. Highlights of the strategy include the construction of a strained enynone‐containing macrolide and the installation of a cyano group in a regioselective manner by a novel molybdenum‐catalyzed hydrostannation of the alkyne.

Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo

“…With an IC 50 of 0.97 nM, borrelidin is a more potent antimalarial compound than artemether, artesunate, or chloroquine (21,22). Its activity is thought to arise from inhibition of ThrRS (41). Previous reports have shown that borrelidin is a noncompetitive inhibitor of ThrRS with respect to threonine and inhibits the amino acid activation step (23).…”

Stereoselectivity of Isolated Dehydratase Domains of the Borrelidin Polyketide Synthase: Implications for cis Double Bond Formation

“…Borrelidin (1), an unusual polyketide with potent cytotoxic, anti-angiogenic and anti-malarial activities, contains both a trans and a cis double bond, as confirmed by total synthesis [16][17][18] and X-ray diffraction analysis. [19] Both bor modules 2 (trans double bond) and 3 (cis double bond) contain the expected set of reducing domains (KR and DH) ( Figure 1).…”

Nitroxide‐Catalyzed Alcohol Oxidations in Organic Synthesis

“…The selectivity of the TEMPO-catalyzed reactions are generally preserved, and these reagents were successfully applied toward the synthesis of multifunctional molecules (Schemes 12.37, 172 12.38, 173 and 12.39 174 ). One advantage of these reactions is that the oxidant is a solid and a more careful stoichiometric control over the oxidation can be achieved than, for instance, when using bleach.…”