An Improved and Practical Method for Synthesizing of α-Sanshools and Spilanthol

Abstract

An efficient and practical route for the synthesis of α-sanshools and spilanthol is described herein. Several modifications of an existing method enabled the preparation of the (2E,6Z,8E,10E)-tetraene precursor of hydroxy-α-sanshool in good yield. A highly selective Wittig reaction employing newly synthesized phosphonium salt with low deliquescence and long-term stability yielded the desired Z-form tetraene. This improved methodology was shown to be applicable to the efficient synthesis of α-sanshool and spilanthol.

Discovery of Spilanthol Endoperoxide as a Redox Natural Compound Active against Mammalian Prx3 and Chlamydia trachomatis Infection

“…Removal of solvent in vacuo gave 6 as a mixture of diastereomers (0.174 g, 1.05 mmol, 99%). NMR data matched that in [26]. 1 H NMR (400 MHz, Chloroform-d) mixture of diastereomers δ 11.56 (s, 1H), 7.15-7.01 (m, 1H), 6.42-6.18 (m, 1H), 6.09-5.91 (m, 1H), 5.84 (ddt, J = 15.6, 6.1, 1.5 Hz, 1H), 5.76-5.37 (m, 2H), 2.46-2.13 (m, 4H), 1.86-1.63 (m, 3H).…”

A Review of the Chemistry and Biological Activities of Acmella oleracea (“jambù”, Asteraceae), with a View to the Development of Bioinsecticides and Acaricides

“…The most recent attempt reported in the literature for the synthesis of spilanthol was performed by Nakamura in 2020, wherein a highly selective Wittig reaction produced the desired Z -form tetraene through the employment of newly synthesized phosphonium salt with low deliquescence and long-term stability. The final yield was 47% [ 80 ] ( Scheme 5 ).…”

“… Synthesis of spilanthol through the employment of AZADOL as a catalyst of the stereoselective Wittig reaction [ 80 ]. …”

Synthesis of Bungeanool, Isobungeanool, Dihydrobungeanool, Tetrahydrobungeanool, Hazaleamide, Lanyuamide III, and Analogues

“…Therefore, we set out to synthesize 1 using methods that would be amenable to also synthesizing 2-4 and 11, as well as hydroxylated analogue 12, and natural products hazaleamide (13) 22 and lanyuamide III ( 14), 5 which are dehydroxylated analogues of bungeanool, and isobungeanool, respectively (Figure 2). We have previously reported stereoselective syntheses of both 5 23,24 and 7, 25 and for the reasons mentioned above, we targeted the synthesis of all of the bungeanools 1-4 using a flexible general route that was also amenable to the synthesis of analogues such as 11-14, so that these compounds could more accessible for further studies. Since all of these targets possess the same 2E-,4E-diene moiety found in 7, we aimed to use the alkynoate isomerization reaction that is catalyzed by the combination of Ph3P and PhOH that is exemplified by the conversion of A to B, to generate the C1-C5 portion of these compounds, as we did in our synthesis of 7 (Scheme 1).…”

“…We have previously reported the stereoselective syntheses of both 5 23 24 and 7 , 25 and, for the reasons mentioned above, we targeted the synthesis of all the bungeanools 1 – 4 using a flexible general route that was also amenable to the synthesis of analogues such as 11 – 14 , so that these compounds could be more accessible for further studies. Since all of these targets possess the same 2 E ,4 E -diene moiety found in 7 , we aimed to use the alkynoate isomerization reaction that is catalyzed by the combination of Ph 3 P and PhOH, as exemplified by the conversion of A into B (Scheme 1 ), to generate the C1–C5 portion of these compounds, as we did in our synthesis of 7 .…”