Jaspines A and B: two new cytotoxic sphingosine derivatives from the marine sponge Jaspis sp.

Enantioselective Syntheses of Pachastrissamine and Jaspine AviaHydroxylactonization of a Chiral Epoxy Ester

“…The 1 H-and 13 C-NMR data, as well as the specific rotation value of 1, matched those reported for the natural product. 1,2) The conversion of 1 to jaspine A (2) proceeded uneventfully in an 89% yield by treating 1 with tetrahydro-2-furanol in the presence of p-toluenesulfonic acid.…”

“…1) Shortly after this discovery, Debitus et al also isolated the same compound together with another anhydrophytosphingosine derivative from the marine sponge Jaspis sp., and named them jaspine B (1) and jaspine A (2); the hydrochloride of 1 was shown to display marked cytotoxicity (IC 50 ¼ 0:24 mM) against the A549 human lung carcinoma cell line. 2) Prompted by the intriguing biological activity and unique molecular architecture featuring an all-cis 2,3,4-trisubstituted tetrahydrofuran structural motif, many studies have been made on the synthesis of 1 using various approaches. 3) As many as 17 syntheses of 1 have already been reported which can be categorized into 5 groups according to the source of chirality: i) chiral natural products (L-serine, carbohydrates, and tartaric acids); [4][5][6][7][8][9][10][11][12] ii) commercially available D-ribo-phytosphingosine; 13,14) iii) asymmetric conjugate addition of a chiral amide; 15) iv) Sharpless asymmetric epoxidation/dihydroxylation; [16][17][18][19] and v) asymmetric aldol reaction.…”

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

“…It is a naturally occurring, novel anhydrophytosphingosine derivative that contains an all-cis-2,3,4-trisubstituted tetrahydrofuran ring with the (2S,3S,4S) absolute configuration and exhibits cytotoxic activity against various human cancer cell lines. [1][2][3][4][5][6][7][8][9] Recently, Delgado and colleagues reported that 1 causes autophagy mediated by dihydroceramides in human A549 lung cancer cells. 6) Andrieu-Abadie and colleagues also reported that 1 induces apoptosis in murine B16 melanoma cells through an increase in intracellular ceramide levels resulting from inhibition of the activity of sphingomyelin synthase.…”

“…30) However, this route is not suitable for scalable synthesis because of the low yield of the dirhodium(II)-catalyzed C-H amination reaction. Herein, we report the practical syntheses of pachastrissamine (1), 2-epi-pachastrissamine (2), and the 2-epimer of the pyrrolidine analogue (4) from commercially available diethyl D-tartrate (14).…”

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

“…1). 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 7-10) 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.…”