Stereoselective, biogenetically patterned synthesis of (.+-.)-aplysistatin

Inter‐ and Intramolecular [2+2]‐Photocycloaddition of Tetronates − Stereoselectivity, Mechanism, Scope and Synthetic Applications

“…It was extracted with EtOAc (4 ϫ 30 mL) and the combined organic layers were dried (Na 2 SO 4 ). After filtration and evaporation of the solvent under reduced pressure crude 5-(but-3-enyl)-4-hydroxyfuran-2(5H)-one (19) was obtained as a yellow solid which was recrystallized from P/EtOAc to give the title compound as colorless, crystalline solid (1.07 g, 6.97 mmol, 84%, 70% from 18). M.p.…”

“…This procedure was adapted from White et al [19] To a solution of LDA (1  in THF, 17.0 mL, 17.0 mmol) was added methyl hept-6-enoate (14, 2.40 g, 17.0 mmol) in a dropwise fashion and the mixture was stirred at this temperature for 1 h. During this period TMS-Cl (4.20 mL, 32.9 mol) was slowly added and the mixture was extracted with H 2 O (2 ϫ 20 mL). The remaining organic phase was dried (Na 2 SO 4 ), filtered and the solvent was evaporated under reduced pressure to give a brown oil.…”

“…In the former case (C3 substitution), methyl 6-oxohexanoate was prepared from cyclohexanone (13) following a procedure reported by Semple et al [18] The aldehyde was transformed into the corresponding alkene (14) using standard Wittig conditions. Following a literature procedure reported for related compounds, [19] the tetronic acid core was subsequently installed by acylation with chloroacetyl chloride followed by base-assisted cyclization. The reaction sequence was not further optimized.…”

Stereoselective Halogenation in Natural Product Synthesis

“…Upon treatment of 284 with TBCO, the desired product 285 was obtained as a minor component of a 19:81 diastereomeric mixture in poor yield. [111] On the other hand, the groups of Hoye [112] and of White [113] both employed the mercury(II)-mediated indirect approach for the synthesis of 289 . The direct cyclization 287 with TBCO was again not effective.…”

“…Upon treatment of 284 with TBCO,t he desired product 285 was obtained as aminor component of a19:81 diastereomeric mixture in poor yield. [111] On the other hand, the groups of Hoye [112] and of White [113] both employed the mercury(II)-mediated indirect approach for the synthesis of 289.The direct cyclization of 287 with TBCO was again not effective.F ollowing Hoyes multistep procedure, [110] White and co-workers converted 287 to the net bromocyclization products in al ow but improved yield. Them ajor diastereomer 288 had the desired configuration and was readily converted to 289.Asimilar mercury-(II)-based approach was also employed for the synthesis of palisadin Ab yT anaka and co-workers.…”