Total Synthesis of the Postulated Structure of Fulicineroside

Abstract

A total synthesis of the proposed structures of fulicineroside and its aglycone fulicinerine is reported. The tetrasubstituted dibenzofuran substructure was accessible either through a Pd-mediated ortho-metalation or by an Ir-catalyzed meta-borylation. The synthesis of the β,β,α-linked trisaccharide consisting of D-olivose, L-rhodinose, and L-rhamnose was challenged by the unprecedented β-linked rhodinose. A Pd-catalyzed β-selective glycosylation of a 4-epi-rhodinose and a subsequent Mitsunobu inversion provided selectively the β-linked L-rhodinose-L-rhamnose disaccharide. Comparison with the reported data for the natural product and the aglycone suggests a misassignment of the structure of the natural product.

Applications of Mitsunobu Reaction in total synthesis of natural products

“…It was highly active toward crown gall tumors and Gram‐positive bacteria such as Staphylococcus aureus and Bacillus subtilis . The efficient and stereoselective total synthesis of the proposed structures of fulicineroside and its aglycone fulicinerine achieved and accomplished by Koert and co‐workers in 2013 . Synthesis of fulicinerine ( 338 ) is explained in Scheme and begins with the preparation of the diol 340 from aldehyde 339 as starting material in several steps.…”

“…Thiol‐Mitsunobu reaction of 340 with PTSH by using PPh 3 and DIAD in THF at room temperature obtained the monothioether 341 selectively. The latter was converted into the thioether sulfone 342 under molybdate‐catalyzed oxidation condition and then via thiol‐Mitsunobu reaction with PTSH in the presence of DIAD and PPh 3 in THF at room temperature . Final, the resulting compound transformed into desired natural product 338 .…”

“…The carbonate 354 was converted into 356 by latter reactions including benzoylation, TBS cleavage and Mitsunobu inversion. The subsequent diimide reduction of compound 356 leading to 353 …”

Di-tert-butylsilyl Bis(trifluoromethanesulfonate)

“…The reaction was applied to obtain aglycone fulicinerine. 6 (F) Treating compounds 19a-b (2 equiv) with t-Bu 2 Si(OTf) 2 (1 equiv), Guerra and co-workers have afforded the corresponding bismalonates 20a-b, which they then used for the regioselective bisfunctionalization of C 60 . 8 (G) Asymmetric bifunctional silyl ether (ABS) prodrugs of chemotherapeutics (camptothecin, dasatinib, and gemcitabine) were obtained in one step by reacting a dichlorodialkyl silane (i-Pr, Et,) or tBu 2 Si(OTf) 2 with the pendant alcohol on the chemotherapeutic.…”

“…2 It acts as protecting group for 1,3-diols to improve yield and stereoselectivity of organic reactions, 3 for 1,2-diols in a synthesis of dienophiles 4 and 1,4-diols to obtain 3,6-bridged glycosyl donors 5 and to receive natural products. 6 Triethylsilyl ether, isopropylidene ketal would perform the same role as the t-Bu 2 Si(OTf) 2 ; however, their acidic removal could be problematic in some cases. 7 The bridging di-tert-butylsilylene can be cleaved to give the corresponding fullerene polyols.…”