Total Synthesis and Biological Evaluation of Glycolipids Plakosides A, B and Their Analogs

Abstract

Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday for his outstanding contributions to organic and bioorganic chemistryThe total synthesis of plakosides A (1) and B (2), and their designed analogs 3 ± 10 was accomplished. The convergent strategy employed involved construction of the individual building blocks employing the Sharpless asymmetric dihydroxylation and the Charette asymmetric cyclopropanation reactions to introduce the desired configuration, followed by their couplings and final elaboration. Thus, key intermediates 12 ± 14 were prepared in their optically active forms and joined through a glycosidation reaction and amide-bond formation to yield the target molecules after appropriate elaboration and final deprotection. The synthesized compounds 1 ± 10 were evaluated for their immunosuppressive properties in vitro and found to be only modestly active.

An expedient synthesis of d-callipeltose

“…For this purpose, several leaving groups, including mesylate, 15 triflate 15 and imidazolyl sulfonate, 16 were examined, but only the nosylate group 17 could be displaced at an acceptable rate without decomposition. The nosylate 7 was obtained by the action of nosyl chloride and pyridine on 6 in 80% yield along with ca.…”

Enantioselective [2+1] Cycloaddition: Cyclopropanation with Zinc Carbenoids

“…this method to obtain cyclopropane containing fragments required for the synthesis of the biologically active compounds (12S,13S,15S)-cyclopropyl epithilone A [68], plakosides A and B [69].…”

Synthesis of a Prenylated and Immunosuppressive Marine Galactosphingolipid with Cyclopropane-Containing Alkyl Chains: (2S,3R,11S,12R,2′′′R,5′′′Z,11′′′S,12′′′R)-Plakoside A and Its (2S,3R,11R,12S,2′′′R,5′′′Z,11′′′R,12′′′S) Isomer

“…[2] The unique structure of plakoside A (1), together with the fact that only 5 mg of 1 could be secured from 57 g (dry weight) of the sponge, [1] encouraged us to explore a synthetic route to this compound. [4] Results and Discussion We assumed that the two cyclopropane-containing side chains in a given molecule have the same absolute configuration due to the enantioselective biocyclopropanation process.…”