Asymmetric Synthesis of 1,2-Dioxolane-3-acetic Acids:  Synthesis and Configurational Assignment of Plakinic Acid A

Abstract

The first asymmetric synthesis of 1,2-dioxolane-3-acetic acids is reported. Key features include the stereoselective opening of enantiomerically enriched oxetanes by hydrogen peroxide, conversion of the resulting 4-hydroperoxy-2-alkanols to 3-alkoxy-1,2-dioxolanes, and Lewis acid mediated homologation of the latter with a thioester silyl ketene acetal. The approach is modeled on 3,5-dimethyl-5-hexadecyl-1,2-dioxolane-3-acetic acid (1a), an unnamed natural product, and an optimized strategy is applied to the synthesis of four stereoisomers of plakinic acid A (2), allowing a configurational assignment of this incompletely characterized natural product.

Enantio‐ and Diastereoselective Synthesis of exo‐Peroxyacetals: An Organocatalyzed Peroxyhemiacetalization/oxa‐Michael Addition Cascade

“…[1][2][3][4][5] However,t odate, the corresponding catalytic enantioselective strategies for the synthesis of chiral peroxides are less explored. [6][7][8][9] Moreover,asper our knowledge,there is still ascarcity of methods for the catalytic enantio-and diastereoselective synthesis of peroxides.…”

Peroxy natural products

“…75 The first asymmetric synthesis of 1,2-dioxolane-3-acetic acids has been reported, and a further optimized strategy was applied to the synthesis of four stereoisomers of plakinic acid A, 76 allowing a complete configurational assignment of plakinic acid A. 77 One ω-phenyl polyketide peroxide, plakinic acid L 149, was isolated from a two-sponge association of P. halichondroides and X. deweerdtae. 49 Synthesis of four possible diastereomers of plakortide E 78 established the absolute configuration of plakortide E as shown.…”

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

“…The intermediate hydroxydioxolanes 131'a , b were used in the second step without isolation (Scheme 30) [260]. A series of analogues of plakinic acids were synthesized by the modification of the peroxyketal moiety of dioxolanes 132a and 132b [260]. …”

“…Diastereomers of plakinic acid A, 162a and 162b were synthesized starting from dioxolane (( R )-3-((2 R ,3 E ,6 S ,7 E )-2,6-dimethyl-8-phenylocta-3,7-dienyl)-5-(2-methoxyethoxy)-3,5-dimethyl-1,2-dioxolane) ( 159 ) [260]. In the first step, dioxolane 159 was treated with (1-(ethylthio)vinyloxy)-trimethylsilane in the presence of TiCl 4 to obtain S -ethyl 2-(( R )-5-((2 R ,3 E ,6 S ,7 E )-2,6-dimethyl-8-phenylocta-3,7-dienyl)-3,5-dimethyl-1,2-dioxolan-3-yl)-ethanethioate ( 160 ).…”