Practical Synthesis of Pachastrissamine (Jaspine B), 2-<i>epi</i>-Pachastrissamine, and the 2-<i>epi</i>-Pyrrolidine Analogue

Abstract

The practical syntheses of pachastrissamine (jaspine B), 2-epi-pachastrissamine, and the 2-epimer of the pyrrolidine analogue were accomplished via the stereoselective reduction of an allylketone derived from commercially available diethyl D-tartrate and the cross-metathesis of an allyltetrahydrofuran or allypyrrolidine with 1-tridecene as key steps.

Synthetic Studies on a Pachastrissamine Sulfur Analogue: Synthesis of a 4-<i>epi</i>-Sulfur Analogue

“…We next examined the nucleophilic substitution of 12 with a thiolate anion as a nucleophile. Treatment of 12 with sodium sulfide pentahydrate (Na 2 S·5H 2 O) in N,N-dimethylformamide (DMF) at room temperature to 100°C afforded not the desired thiol 13 but the eliminated product 14, in contrast to our previous case of the aza analogue 3, 31) in which the reaction of the tosylate of the 4-epimer of 9 with sodium azide furnished the corresponding nucleophilic substitution product in high yield. 31) This unfortunate result made us investigate an alternative synthetic procedure to 4 using tandem thiolation-cyclization from 12 via the ditosylate 15 (Chart 3).…”

“…The synthesis was started from 9, 31) as shown in Chart 2. Treatment of 9 with 1-tridecene in the presence of Grubbs second-generation catalyst in CH 2 Cl 2 under reflux conditions generated a mixture of the (E)-and (Z)-isomers of the alkene 11, which was hydrogenated using Pd/C in EtOAc to afford 8.…”

“…On the basis of our previous syntheses of 1-3, 31) the desired analogue 4 would be derived from the tetrahydrothiophene 6 via S N 2-type amination at the 4-position. Because olefin cross-metathesis of sulfur-containing compounds is often problematic, [49][50][51][52] we planned to extend the alkyl side chain before the introduction of a sulfur atom.…”

“…It exhibits cytotoxic activity against various cancer cell lines [1][2][3][4][5][6][7][8][9] and induces programmed cell death, such as autophagy 6) and apoptosis [7][8][9][10] in some cancer cells. Owing to its interesting structural features and significant biological properties, many researchers have reported the total synthesis of 1 [3][4][5][6][7] and its stereoisomers 5,6,[20][21][22][23][24][25][26][27][28][29][31][32][33][34][35][36][37][38][39][40][41] to date. In addition, several analogues of 1 have been synthesized and their biological activities have been investigated.…”

“…Very recently, we succeeded in the synthesis of 1, 2-epi-pachastrissamine 2, and the 2-epi-aza analogue 3. 31) Our synthetic route to 1-3 would be useful for the synthesis of their derivatives bearing various alkyl side chains, because inexpensive diethyl D-tartrate is employed as a starting material and the alkyl side chain is introduced at a later stage. Here, we report studies on the synthesis of a sulfur analogue of pachastrissamine, which is based on the synthetic strategy for 1-3, and the synthesis of the 4-epi-sulfur analogue 5.…”