Page 22 - I. Chemical biology and drug discovery

[I. Chemical biology and drug discovery-12]

Total synthesis of Gramistilbenoids A, B, and C

Dipesh S Harmalkar¹˙#, Sreenivasulu Godesi¹˙#, DongIK Kwak¹, Minkyoung Kim¹, Kyeong Lee¹˙*

¹College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Korea

Gramistilbenoids are the first naturally occurring diphenylethylenes, possessing a hydroxyethyl unit isolated from
the bamboo orchid Arundina graminifolia. Most of the natural products are not abundant in nature, and thus, their
synthesis is advantageous to carry out diverse structure-activity relationship (SAR) study. We report the first total

synthesis of Gramistilbenoids A, B, and C, with overall yields of 10, 2, and 8% respectively. These natural products

were synthesized using key reactions, such as Horner–Wadsworth–Emmons olefination, Stille coupling, and
hydroboration-oxidation. Stilbene and its derivatives have attracted substantial attention from the scientific
community due to their numerous human health benefits, including chemoprevention and antitumor activity. As

part of our drug development program, our in-house chemical library containing these natural products and their
synthetic analogs were evaluated for different biological assays including anti-NV activity. The intermediates and

natural products were tested for anti-norovirus activity in qPCR assay in HG23 cell lines (Norwalk virus). SAR studies
of vinyl stilbenes exhibited potent anti-NV activity with EC50 values ranging from 1 to 2µM.