An efficient and robust synthesis of amorfrutin A

A unified strategy for the synthesis of amorfrutins A and B and evaluation of their cytotoxicity

“…In the course of our syntheses, we could show that compound 3 (Scheme 1) is easily accessible in large quantities from commercial 3,5-dimethoxybenzaldehyde in only 6 steps in a total yield of 63% 34 . Thus, 3 seems to be an ideal starting material for synthesizing the two amorfrutins A and B.…”

“…Regarding the synthesis of amorfrutins, 3 was converted into methyl ester 4 by reaction with MeI in the presence of Cs2CO3 in 98% yield. The reaction of 4 34,36 with K.H. and prenyl chloride gave a mixture of 5 (as a product of C-alkylation) 34,37 , and 6 (as an etherification product) 13 .…”

“…The reaction of 4 34,36 with K.H. and prenyl chloride gave a mixture of 5 (as a product of C-alkylation) 34,37 , and 6 (as an etherification product) 13 . Whereas, from the reaction with geranyl chloride, a mixture of 7 (from a C-alkylation) 17 and 8 (C-and O-alkylation) was obtained.…”

“…111-113°C (lit. : 34 3-(3,7-dimethylocta-2,6-dien-1-yl  = 3085vw, 3061vw, 3027w, 2952w, 2916w, 2854w, 1725w, 1651s, 1609m, 1573m, 1496w, 1452m, 1436m, 1404m, 1376m, 1280vs, 1226s, 1194m, 1155s, 1112s, 1077w, 1043w, 1030w, 1007m, 962w, 912w, 882w, 836w, 807m, 770m, 748m, 699s, 659w, 608m, 557w, 488w, 470w cm -1 ; 3086vw, 3062vw, 3026vw, 2931w, 2859w, 1725s, 1602s, 1584m, 1496w, 1453m, 1432m, 1382w, 1346w, 1317m, 1282m, 1260s, 1225m, 1195s, 1157vs, 1099s, 1081m, 1049s, 1030m, 993w, 949w, 923w, 881w, 827m, 817m, 788w, 748m, 700s, 639w, 609w, 574w, 561w, 490w, 461w cm -1 ; UV/Vis ( 3-(3,7-dimethylocta-2,6-dien-1yl)-2-hydroxy-4-methoxy-6-phenethyl benzoic acid (2) From 7: A solution of 7 (100 mg, 0.24 mmol) in MeOH (5 mL) was added to a 40°C solution of KOH (84 mg, 1.5 mmol) in MeOH/H2O (7:1, 40 mL), and the mixture was heated under reflux for 10 h. Usual workup followed by chromatography (silica gel, nhexane/ethyl acetate, 3:1) gave 2 (81 mg, 84%) as a colorless solid. 2671w, 2592w, 2537w, 1633s, 1607s, 1571m, 1496m, 1453m, 1430m, 1401m, 1380m, 1348w, 1266vs, 1221s, 1188m, 1170m, 1149m, 1113s, 1077m, 1046w, 1030w, 1003w, 983w, 923w, 902m, 858w, 837m, 819m, 804m, 773m, 749s, 734m,696s, 679m, 663w, 608m, 562w, 533w, 494m…”

“…However, the complex also appears to be important in treating cancer 12,16,22 , inflammations 23,24, and for impending the age-related decline of metabolism 13,15,25-27 . Several syntheses have been published to access amorfrutins A and B whereby the former has been the focus of scientific interest. In contrast, the number of syntheses for the latter has remained small [28][29][30][31][32][33][34] . However, of particular interest are synthetic strategies that allow in principle to synthesize as many as possible of the previously known amorfrutins and, if necessary, analogs in a unified manner 31,33 .…”