Total Synthesis of Evelynin B and Taccabulin D

Abstract

Biosynthetic retro-dihydrochalcone derivatives represent a significant class of compounds with broad and remarkable potential biological properties, such as anti-ulcer, 1 antihistamine, 2 and anti-microbial, 3 and anti-malarial activities. 4 Therefore, it is not surprising that many synthetic methods have been developed for these types of compounds. [5][6][7][8][9][10][11] Evelynin B and taccabulin D (Fig. 1) are two novel retrodihydrochalcone-typed compounds, isolated from fresh roots and rhizomes of Tacca chantrieri and T. integrifolia by Moberry and co-workers in 2013. 12 Compounds 1 and 2 have antiproliferative activities against three cancer cell lines: HeLa, A549 and PC-3. 12 The IC 50 values of evelynin B (1) against HeLa, A549, and PC-3 cells are 8.8, 8.3 and 5.0 μM, respectively, while those of taccabulin D (2) are 28.9, 40.3 and more than 50 μM.We have initiated the total synthesis of the two new compounds in order to investigate the potential bioactivity of the derivatives. We now report the concise efficient total syntheses of evelynin B (1) and taccabulin D (2) from the accessible starting material trimethoxybenzene which would provide enough compounds for further biological studies. Results and discussionOur initial retrosynthetic analysis of 1 is outlined in Scheme 1. We envisaged that a Claisen-Schmidt reaction could be used to construct the main skeleton of evelynin B and taccabulin D. Aldehyde 6, in turn, could be obtained from a cheap starting material 1,2,3-trimethoxybenzene.The synthesis of evelynin B is illustrated in Scheme 2. 1,2,3-Trimethoxybenzene was oxidised with 30% HNO 3 to form 1,4-benzoquinone 3 in 80% yield. 13 Reduction of 3 with Na 2 S 2 O 4 in EtOAc for 40 min smoothly gave diphenol 4 in 84% yield. 14 Dialkylation of diphenol 4 with BnBr in refluxing acetone affords ether 5 in 86% yield. 15 Aldehyde 6 was available through Vilsmeier reaction from ether 5 in 81% yield. 14 Then, aldehyde 6 was reacted with 3,4-methylenedioxyacetophenone 7 through

The First Synthesis of Baphicacanthin A, a Natural Phenoxazinone Alkaloid Derived from Baphicacanthus cusia

“…Purification of residue via flash column chromatography on silica gel (EtOAc/ n ‐hexane = 1:20~1:10) afforded 6 in 75% yield (624 mg) as a brown oil. The NMR spectra data were consistent with the previously reported data …”

“…The biaryl ether 2 was expected to be synthesized from properly protected polyhydroxyphenol 3 by nucleophilic aromatic substitution with fluoronitrobenzene, and subsequent one‐pot hydrogenation/hydrogenolysis for the nitro reduction and benzyl deprotection. The phenol 3 was planned to be prepared from known benzaldehyde 4 by Baeyer–Villiger oxidation.…”

“…As shown in Scheme , our synthesis of baphicacanthin A ( 1 ) commenced with the preparation of the known benzaldehyde 4 from commercially available 2,6‐dimethoxy‐1,4‐benzoquinone 5 . Reduction of quinone 5 using Na 2 S 2 O 4 and subsequent benzylation readily afforded dibenzyloxybenzene 6 in 75% yield for two steps.…”

Design and synthesis of piezochromic materials exploring intermolecular charge transfer: chalconoids bound to thep-sulfonatocalix[6]arene macrocycle

“…The respective ketone underwent ClaisenÀSchmidt condensation under basic conditions (Scheme 1) resulting in a series of chalcone derivatives: (2E,4E)-1,5-diphenylpenta-2,4-dien-1-one (C1), 55 (E)-1-phenyl-3-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (C2), 56 (E)-1-(pyridin-2-yl)-3-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (C3), 57 (E)-1-(4-(benzyloxy)-3-methoxyphenyl)-3-(2,4,6-trimethoxyphenyl)prop-2-en-1-one (C4) 58 and (E)-1-(4-(benzyloxy)-3-methoxyphenyl)-3-phenylprop-2-en-1-one (C5) were synthesized as per the general procedure (for details see ESI †) with 70-90% yield and purified with silica-gel column chromatography. All materials have been extensively characterized through 1 H, 13 C, COSY NMR (Fig.…”