Total synthesis of FR901464: second generation

Cytotoxic Spliceostatins from Burkholderia sp. and Their Semisynthetic Analogues

“…The 1 H, 13 C, and HMBC data of 4 are summarized in Table 1, and the key HMBC and ROESY correlations that defined the structure and configuration are illustrated in Figure 3.…”

“…The relative configuration at C-4 was determined by the observation of a ROESY correlation between H-4 at δ H 3.64 and H-6 at δ H 5.57, which required a 4R configuration. The 1 H, 13 C, and HMBC data of 7 are summarized in Table 1.…”

“…Spliceostatin E (8) represents a molecular framework that is distinctively different from those of the other analogues of this class. 8,9,[12][13][14]20,21 The molecular formula of spliceostatin F (9) was determined by HRESIMS to be C 28 H 42 ClNO 8 . The NMR spectroscopic assignment for the core structure of 9 was essentially identical to that of thailanstatin B (10).…”

Comparison of Splicing Factor 3b Inhibitors in Human Cells

“…No.2663 (Scheme 1). [5][6][7] Since then, some of the readily available FR901464 analoguesspliceostatin A [8] and meayamycin [9] among others [10][11][12] -have been widely used to elucidate the mechanisms of pre-mRNA splicing and SF3b-related diseases. [2,4,[13][14][15][16][17][18][19][20][21][22][23][24][25] In 2011, herboxidiene (GEX1A) was also found to be an inhibitor of SF3b, [26][27][28][29][30][31] and our group reported meayamycin B as a new FR901464 analogue (Scheme 1).…”

Total Syntheses of FR901464

“…The Kitahara group described their revised total synthesis of FR901464 in 2006, which addressed some of the aforementioned synthetic problems. 13 The preparation of acid fragment 29 is shown in Scheme 5a. Ethyl (S)-(-)-lactate, already containing the C4' stereocenter, was protected as its TBS ether and subsequently reduced with DIBAL-H to afford aldehyde 28 according to the literature.…”