Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields. Keywords: dehydration; flavonoid; hydnocarpin; Mitsunobu; silybin; Introduction Flavonolignans

• hepatotoxicity in vitro as well as in vivo [10][11]. The flavonolignan hydnocarpin (4, Figure 1) was first isolated in 1973 from Hydnocarpus wightiana [12], and its structure was at first assigned erroneously as what is now named hydnocarpin D (2, Figure 1) (for details see below) [13]. The actual hydnocarpin D

• provided [15]. Hydnocarpin-type compounds (2, 4 and 6; Figure 1) are formally dehydrated analogs of silymarin flavonolignans with flavanone-3-ol (3-hydroxyflavanone) structure (silybin A and B, isosilybin A and silychristin A). Hydnocarpin and its derivatives show interesting biological activities such as