Total synthesis of a fully protected palytoxin carboxylic acid

Abstract

The total synthesis of a fully protected palytoxin carboxylic acid was achieved from eight building blocks 1, 2, 4, 6, 8, 9, 11, and 13. The C.22-C.23 and C.37-C.38 bonds were formed via Wittig olefination, followed by hydrogenation. The Ni(II)/Cr(II)-mediated coupling reaction was utilized for formation of the C.7-C.8 and C.84-C.85 bonds. The TlOH-accelerated diene synthesis was applied for formation of the C.75-C.76 bond. The C.98-C.99 olefinic bond was introduced by a Wittig reaction, whereas the C.51-C.52 olefinic bond was introduced by a Horner-Emmons reaction, followed by stereoselective LiBH4/EuCl3 reduction.

Total Synthesis of (−)-Bafilomycin A1: Application of Diastereoselective Crotylboration and Methyl Ketone Aldol Reactions

“…[13] 1996, 100, 1667 ± 1677. [15] Compounds of the structural types 4 ± 6 also show intensive luminescence in solid solutions, that is in textile dyeing on polyester. A detailed discussion of the competition between radiationless deactivation and photoluminescence, which is evidently strongly dependent on the rigidity of the matrix, should become possible based on the emission spectra of solid samples and dyed textile fibers as well as on crystal structure analyses.…”

“…[12] This highly convergent approach would allow for the use of a Suzuki cross-coupling reaction [13] to generate an appropriately protected macrocyclization precursor. While the Stille reaction [14] has found great utility in the assembly of natural products, including in the earlier bafilomycin syntheses, [7,8] there are limited applications of the Suzuki reaction for latestage union of complex intermediates, the most notable of the limited examples being recorded in the palytoxin synthesis by Kishi et al [15] and the rutamycin synthesis by Evans et al [16] The aldol reaction between 2 and 3, which serves as the final CÀC bond forming event in the synthesis, provides an additional opportunity to explore the factors that control the stereochemistry of fragment assembly in methyl ketone aldol reactions. [17] The vinylboronic acid 4 was prepared from olefin 7, which was synthesized from commercially available ester 6 by the previously described diastereoselective allylmetalation sequence (Scheme 2).…”

“…The dyes with sterically demanding substituents, on the other hand, form red crystals that shine intensively in numerous cases. [15,16] The dye library obtained through a highly efficient multicomponent synthesis led us to colorants with glass-forming and solid-state photoluminescent properties. Sterically demanding substituents proved crucial to both properties by determining the packing of the functional p systems, thus paving the way for the exploitation of these interesting dyes in new materials.…”

High Resolution LC-MSn Fragmentation Pattern of Palytoxin as Template to Gain New Insights into Ovatoxin-a Structure. The Key Role of Calcium in MS Behavior of Palytoxins

“…): homo, bishomo-, neo-, and 73-deoxy-palytoxin [5], ostreocin-D (namely 42-hydroxy-3,26-didemethyl-19,44-dideoxypalytoxin) [6], and 42-hydroxy-palytoxin [7]. Structure elucidation of these compounds was carried out by extensive NMR analyses and in most cases through the use of degradation/derivatization reactions [1,5,8]. This kind of study requires relatively high amounts of pure material and, therefore, structures of a number of minor congeners of palytoxin so far identified were not elucidated due to lack of pure material in quantities sufficient to structural investigation.…”

New and Old Challenges in Total Synthesis. From Concept to Practice

“…The synthesis of palytoxin was achieved by Kishi and coworkers [3] 100 years after Fischer's (+)-glucose, bringing us full circle from nature's first synthetic man-made enantiopure compound, to one of its largest.…”