Synthesis of AB and CD Spiroketal of Spongistatin 1

Abstract

The AB (C 1 -C 13 ) and CD (C 17 -C 29 ) spiroketal of spongistatin 1 were prepared diastereoselectively from syn-and anti-3,5-dihydroxy-6-heptenoate derived from 2-deoxy-D-ribose.

Nonanomeric Spiroketals in Natural Products: Structures, Sources, and Synthetic Strategies

“…Lau (2004). Lau and co-workers published a synthesis for the CD spiroketal segment of spongistatin where the strategy was simply to utilize Lewis acid catalysis in the equilibration (Scheme ) …”

“…Upon further treatment with ZnBr 2 , a reversed ratio of 3.4:1 was achieved, favoring the desired spiroketal 171 .

41 Synthesis of the CD Spiroketal Segment of Spongistatin According to Lau et al

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“…Lau and co-workers published a synthesis for the CD spiroketal segment of spongistatin where the strategy was simply to utilize Lewis acid catalysis in the equilibration (Scheme 41). 73 Open-chained ketone precursor 170 underwent cyclization when treated with hydrofluoric acid to furnish a mixture of spiroketal isomers 171 and 172 in a ratio of 1:4.6. Upon further treatment with ZnBr 2 , a reversed ratio of 3.4:1 was achieved, favoring the desired spiroketal 171.…”

“…A. Thermodynamic Methods reason for the stability of the nonanomeric isomer Lewis-acid/metal chelation hydrogen bonding steric effects other reasons Evans (spongistatin) 55 Paterson (spongistatin) 59a Shimizu (spirofungin) 46 DeShong (avermectin) 34 Smith (spongistatin) 57a Kishi (spongistatin) 54a Dias (spirofungin) 47 Sinibaldi (reveromycin) 35 Nakata (spongistatin) 67a Mead (spongistatin) 63 Ley (spongistatin) 71,72a Kishi (salinomycin) 95 Lau (spongistatin) 73 Yamamura (aplysiatoxin) 80 Ireland (aplysiatoxin) 78 Yonemitsu (salinomycin) 96e Kishi (pinnatoxin) 104 Murai (pinnatoxin) 106a,107 Nakata (reveromycin) 82 Brown/Kocienski (salinomycin) 98c Hirama (pinnatoxin) 105b Theodorakis (reveromycin) 83 Albizati/Perron (salinomycin) 102 Nicolaou (azaspiracid) 114 Carter (azaspiracid) 115 B. Kinetic Methods a Smith (lituarine) b, 33 Deslongchamps (insect pheromone) 5b Pihko (pectenotoxin) 31 Heathcock (spongistatin) 65b Kitching (insect pheromones) 38c, d Paquette (spongistatin) 56…”

General and Facile Route to Isomerically Pure Tricyclic Peptides Based on Templated Tandem CLIPS/CuAAC Cyclizations

“…Four different T4 scaffolds were synthesized that contained two CLIPS and two CuAACf unctional groups each ( Figure 2c); for the latter,wechose to place the alkynes on the scaffold (circumvents the undesired risk of explosion with multiple azides on low-molecular-weight compounds) and the azides on the peptides (Fmoc azido amino acids are readily available). [29] All four T4 x scaffolds display very different numbers of rotatable bonds connecting the alkynes to the core (4/2/1/0 for T4 1 /T4 2 /T4 3 /T4 4 ,r espectively). This allowed us to evaluate how this "flexibility" governs the outcome of the reactions.…”