A pot-economical total synthesis of antifungal Sch-725674, 1 is reported. The approach takes advantage of a number of one-pot, sequential transformations, including a phosphate tether-mediated one-pot, sequential RCM/CM/chemoselective hydrogenation protocol, a one-pot tosylation/acrylation sequence, and a one-pot, sequential Finkelstein reaction/Boord olefination/acetonide deprotection procedure to streamline the synthesis route by reducing isolation and purification procedures, thus saving time. Overall, an asymmetric route has been developed that is efficiently accomplished in seven pots from phosphate (S,S)-triene and with minimal purification.
A series of one-pot, sequential protocols was developed for the synthesis of novel macrocycles bearing α,β-unsaturated chemotypes. The method highlights a phosphate tether-mediated approach to establish asymmetry, and consecutive one-pot, sequential processes to access the macrocycles with minimal purification procedures. This library amenable strategy provided diverse macrocycles containing α,β-unsaturated carbon-, sulfur- or phosphorus-based warheads.
The synthesis of the C1−C16 polyol‐containing macrolactone of 13‐desmethyl lyngbouilloside, an unnatural analog of the originally assigned structure of (−)‐lyngbouilloside is reported. Synthesis of the C1−C16 acyclic backbone is achieved via iterative use of a phosphate tether‐mediated one‐pot sequential, RCM/CM/chemoselective diimide reduction, with concomitant use of a regio‐ and diastereoselective cuprate addition using Me2Zn/CuCN ⋅ 2LiCl or Pd‐catalyzed reductive allylic transposition, respectively on bicyclo[4.3.1]phosphate‐containing subunits. Subsequent oxidative cleavage and Roskamp homologation completes the pathway to the C1−C16 acyclic fragment. Two routes to the macrocyclic core were explored with mixed success, (i) a Boeckman‐type acylketene trapping of the C13 secondary carbinol and (ii) an alternative route employing acid‐catalyzed pyran‐mixed ketal formation via reaction of the C7 secondary carbinol with the β‐keto ester using trimethylorthoformate, and subsequent Yamaguchi cyclization.
A pot-economical approach to advanced
polyol subunits is reported.
The key reactions involved are iterative use of a phosphate tether-mediated
one-pot sequential RCM/CM/H2 with subsequent utilization
of either a regio-/diasteroselective cuprate addition or a Pd-catalyzed
reductive allylic transposition. This method highlights the asymmetric
synthesis of 12 complex polyol subunits in 4–6 one-pot sequential
operations with a total of 12–14 reactions, of which 4–5
are catalytic, with minimal workup and purification procedures.
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