Total Synthesis of Polycavernosides A and B, Two Lethal Toxins from Red Alga

Abstract

Polycavernosides A and B are glycosidic macrolide natural products isolated as the toxins causing fatal human poisoning by the edible red alga Gracilaria edulis (Polycavernosa tsudai). Total synthesis of polycavernosides A and B has been achieved via a convergent approach. The synthesis of the macrolactone core structure is highlighted by the catalytic asymmetric syntheses of the two key fragments using hetero-Diels-Alder reaction and Kiyooka aldol reaction as the key steps, their union through Suzuki-Miyaura coupling, and Keck macrolactonization. Finally, glycosylation with the l-fucosyl-d-xylose unit and construction of the polyene side chain through Stille coupling completed the total synthesis of polycavernosides A and B.

Diastereoselective Synthesis of Arabino- and Ribo-like Nucleoside Analogues Bearing a Stereogenic C3′ All-Carbon Quaternary Center

“…At −40 °C, however, major products 3­( R )- 15a and 3­( R )- 15 b were formed with good enantiomeric ratio (er) [97:3; 3­( R )- 15a , b /3­( S )- 16a , b ], albeit in low yield (entry 4). Gratifyingly, both ( l )-valine-Ts , and ( l )-valine-Ns resulted in high er (entries 5 and 6) with an excellent 86% yield for the latter. A 9:1 mixture of 3R, C2-bromo-diastereoisomers 15a / 15b , which both lead to the same radical intermediates later in the synthesis, was observed with ( l )-valine-Ns (entry 6).…”

Synthetic efforts on the road to marine natural products bearing 4-O-2,3,4,6-tetrasubstituted THPs: an update

“…In 2017, Sasaki and co-workers reported an improved version of their previously reported synthesis of polycavernoside A (2a) (vide supra), 55 as well as the application of this protocol to the synthesis of polycavernoside B (2d). 73 55 This is the common precursor to complete both synthesis of 2a and 2d, based on the employment of sugar moieties 73 and 128 for the glycosylation 52 and stannous polyene 74 and 129 for Stille-type coupling, 54 respectively. Thus, Sasaki and co-workers achieved the synthesis of 2a and 2d in 0.96% and 2.0% overall yield aer 23 and 22 steps, respectively.…”

“…In 2017, Sasaki and co-workers reported an improved version of their previously reported synthesis of polycavernoside A (2a) ( vide supra ), 55 as well as the application of this protocol to the synthesis of polycavernoside B (2d). 73 Fragment 83 was again prepared as shown in Scheme 9 without any modifications, albeit synthesis of fragment 92 was modified. The new strategy towards 92 began with the Kiyooka aldol reaction 74 between acetal 120 and known aldehyde 121, 75 affording enantioselectively β-hydroxy ester 122 which was, in turn, converted into Weinreb amide 123 ( Scheme 12 ).…”