Stereocontrolled Synthesis of Left Halves of Halichondrins

Abstract

A stereocontrolled synthesis of the left halves of halichondrins was reported. An intramolecular oxy-Michael reaction under basic conditions was used to construct the [6,6]-spiroketal in a stereocontrolled manner. With this approach, the left halves of halichondrins, homohalichondrins, and norhalichondrins were synthesized.

Total Synthesis of Halistatins 1 and 2

“…The completion of the synthesis is outlined in Scheme . Recently developed Ni­(I)/Ni­(II)-mediated one-pot ketone synthesis was adopted to couple the right half ( 30 ) with the left half ( 6 ) with a 1.0:1.2 molar ratio of coupling partners, to afford ketone 31 in 76% yield …”

Total Synthesis of the Marine Phosphomacrolide, (−)-Enigmazole A, Exploiting Multicomponent Type I Anion Relay Chemistry (ARC) in Conjunction with a Late-Stage Petasis–Ferrier Union/Rearrangement

“…Turning to stage 3 of the Petasis–Ferrier union/rearrangement protocol, we explored the use of Me 2 AlCl, well-known in this venue (Scheme , entries 1–7); unfortunately, only decomposition resulted presumably via a retro-Michael fragmentation . Extensive experimentation proved uneventful; we were not able to isolate the desired, standard ketone product.…”

“…Turning to stage 3 of the Petasis−Ferrier union/rearrangement protocol, we explored the use of Me 2 AlCl, well-known in this venue 5 (Scheme 13, entries 1−7); unfortunately, only decomposition resulted presumably via a retro-Michael fragmentation. 26 Extensive experimentation proved uneventful; we were not able to isolate the desired, standard ketone product. We concluded however that the reaction sequence might proceed to advanced olefin (−)-47, via in situ capture of the rearranged/generated ketone with methylene ylide (PPh 3  CH).…”

First total syntheses of the pro-resolving lipid mediators 7(S),13(R),20(S)-Resolvin T1 and 7(S),13(R)-Resolvin T4

“…Reaction of 7 with 2 equiv lithium trimethylsilylacetylene in the presence of BF 3 •Et 2 O gave the alcohol 17 in 90% yield that was converted to the di-TBS derivative 18 with 1.6 equiv TBSCl in CH 2 Cl 2 in 89% yield. 23 Selective deprotection of the primary TBSether was accomplished with 10-camphorsulfonic acid (CSA) in CH 2 Cl 2 /CH 3 OH at 0 °C to give 19 in 64% isolated yield. Dess-Martin periodinane oxidation of 19 in CH 2 Cl 2 produced the aldehyde 20.…”