Ring-Construction/Stereoselective Functionalization Cascade: Total Synthesis of Pachastrissamine (Jaspine B) through Palladium-Catalyzed Bis-cyclization of Propargyl Chlorides and Carbonates

Abstract

Palladium(0)-catalyzed cyclization of bromoallenes, propargyl chlorides, and carbonates bearing hydroxy and benzamide groups as internal nucleophiles stereoselectively provides functionalized tetrahydrofuran. Cyclization reactivity is dependent on the relative configuration of the benzamide and leaving groups, and on the nature of the leaving groups. This bis-cyclization was used as the key step in a short total synthesis of pachastrissamine, which is a biologically active marine natural product.

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

“…Late-stage introduction of the side-chain makes it easy to synthesize derivatives bearing various side chains at the C-2 position. 7,16,27) To construct the cyclic structure of 5, we planned to employ cyclization of monotosylate 7. Compound 7 would be obtained from 1,2,4-triol 9 via selective tosylation of the primary alcohols catalyzed by dibutyltin oxide (Bu 2 SnO).…”

“…9,10) Because of its novel structural features and impressive biological activity, many total syntheses of 1 have been accomplished. [3][4][5][6][7][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] The stereoisomers of 1 have also been synthesized, 5,6,[20][21][22][23][24][25][26][27][28][29][31][32][33][34][35][36][37][38][39][40] and their biological activity investigated. Interestingly, the 2-epimer 2 6,…”

Recent Advances in Palladium‐Catalyzed Cascade Cyclizations

“…Jaspine B exhibits cytotoxic activity against various tumour cell lines at the nanomolar level and therefore prompts a wide interest in its synthesis 67. Various pachastrissamine derivatives were prepared and reported in separate work 68. Furthermore, propargylic chlorides could be used for the same transformation.…”

Synthesis and Biological Evaluation of Carbocyclic Analogues of Pachastrissamine

“…It was also reported that pachastrissamine and its stereoisomers inhibit sphingosine kinases (SphKs) and atypical protein kinase C [ 5 ]. Because of its intriguing biological activity, it has been an interesting target for synthetic chemists, and various synthetic routes to pachastrissamine have been reported [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. However, the structure-activity relationship (SAR) of pachastrissamine remains relatively unreported.…”