First Synthesis of Shimobashiric Acid C With Acetonide as the Catechol Protecting Group

ABSTRACT

Shimobashiric acid C (SBA‐C) shows excellent hyaluronidase inhibition but its natural isolation yield is only 0.0092 %. We report its first synthesis via a convergent seven‐step route from caffeic and rosmarinic acids in 35% overall yield. Direct protection of D ‐Danshensu ( D ‐DSS) with 2,2‐dimethoxypropane gave an isochroman; the desired acetonide‐protected D ‐DSS building block was instead prepared from methyl rosmarinate via bis‐acetonide formation followed by methanolysis. Acetonide‐protected caffeic acid was synthesized and crystallized in a P ‐1 lattice, where linear hydrogen‐bonded caffeic acid pairs pack with adjacent alkenyl bonds aligned at 3.919 Å for head‐to‐tail solid‐state [2+2] photodimerization. Irradiation at 365 nm gave the acetonide‐protected α ‐truxillic acid building block. The two blocks were condensed via Steglich esterification to give acetonide‐protected SBA‐C methyl ester. Selective deprotection of the acetonide groups was achieved with 55% trifluoroacetic acid in the presence of trace water in nearly quantitative yields. This mild deprotection caused no noticeable side reactions and may be applied to synthesis of other D ‐DSS‐containing phenolic acids, such as salvianolic acids.