A synthesis of FR901464

The Julia Reaction

“…To the best of our knowledge, no stereocontrolled tetrasubstituted olefins have yet been synthesized by means of the Julia olefination. Nevertheless, they can be synthesized by the method described in Table 3.10 [59]. Both sulfoxide-and sulfoximine-based modifications are promising alternatives for the synthesis of pure syn or anti coupling adducts and might lead to the stereocontrolled preparation of olefins.…”

“…In the case of allylic sulfones, the delocalized carbanion can undergo either a-or g-addition, and the use of enals or enones can result in 1,2-or 1,4-addition products. In general, allylsulfonyl anions, derived from non-stabilized sulfones, undergo additions to carbonyls with excellent aselectivities (reaction 3.17 [59]; Scheme 3.16). The situation is more complex with a,b-unsaturated compounds, but conditions have been defined that lead with high preference to adducts resulting from 1,2-addition (reaction 3.18) [60].…”

The development and application of small molecule modulators of SF3b as therapeutic agents for cancer

“…The groundbreaking work of the Jacobsen group described the first total synthesis of FR901464 [23] and subsequently, important structure–activity relationship (SAR) data [24]. This was followed by several novel approaches to the total synthesis that also reported the generation of several novel analogs [25–29]. Just before the identification of the target of FR901464, workers reported the synthesis of an analog of this compound (meayamycin) that was more stable and more cytotoxic than the parent molecule [29].…”

Syntheses of spliceostatins and thailanstatins: a review

“…Three groups utilized 4-formyl-2,2,5-trimethyl-3-oxazolidine (24) [21], derived from relatively inexpensive ʟ-threonine (<$1/g in bulk) as a chiral pool precursor for the amine stereocenter of the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran fragment. In Kitahara's synthesis [8,9], the Wittig olefination of 24, followed by a catalytic hydrogenation, removal of the dimethylaminal protecting group, and lactonization gave 25 as a mixture of diastereomers (Scheme 2). The further transformation of 25 afforded the dihydropyran 26, which upon catalytic hydrogenation over Pt 2 O and then low-temperature DIBAL reduction afforded the all-cis tetrasubstituted tetrahydropyran 27.…”