Asymmetric total synthesis of paecilomycin E, 10′-epi-paecilomycin E and 6′-epi-cochliomycin C

Abstract

The asymmetric total syntheses of naturally occurring resorcylic acid lactone paecilomycin E and two of its structural congeners have been reported in this article. The major highlight of the synthetic venture is the application of the late stage Mitsunobu macrolactonization method (as it is difficult to achieve the desired products through the standard carboxyl activation method) of a properly functionalized seco-acid. The macrolactonization precursor was synthesized by applying an "E"-selective Julia-Kocienski olefination of a highly functionalized aromatic aldehyde and a sulphone, which constitutes all the stereocenters (C4', C5', C6' and C10'; 3S,7R,8R,9S) in the target molecule.

Properties of a flavonol-based photoCORM in aqueous buffered solutions: influence of metal ions, surfactants and proteins on visible light-induced CO release

“…Several studies of the binding properties of avonols to serum albumin proteins using uorescence spectroscopy have been previously reported. [54][55][56][57][58][59][60][61][62] In the case of 2a, we selectively examined the uorescence properties of both the avonol and the tryptophan residues of the protein to probe the 2a/albumin interaction. Addition of aliquots of BSA to the avonol in TRIS : DMSO (96 : 4% v:v, pH ¼ 7.4) results in a saturatable increase in the intensity of the avonol T* emission band ( Fig.…”

Chemical syntheses of the cochliomycins and certain related resorcylic acid lactones

“…Our route 19 to the first two of these (viz. h then congener A (7) (91%) was obtained while extended exposure of the same substrate to the same conditions resulted in acetonide group cleavage and formation of the previously reported RAL zeaenol (14) which was obtained in 84% yield. Thus, Mitsunobu coupling of keto-acid 104 with the homochiral 2°-alcohol ent-26 gave ester ent-105 (92%) and this underwent an RCM reaction to give neocosmosin A (ent-92) (67%), the structure of which was confirmed by single-crystal X-ray analysis.…”

“…In the course of structurally characterizing the cochliomycins, it was noted 5 that congener C (9) is the chlorinated derivative of co-isolated paecilomycin F (13) ( Figure 3), a previously reported RAL that displays anti-malarial properties. Other RALs also isolated alongside compounds 7-9 were zeaenol (14), LL-Z1640-1 (15) and LL-Z1640-2 (16). During the course of isolating cochliomycins D, E and F (10, 11 and 12, respectively), cochliomycin A (7), zeaenol (14), LL-Z1640-1 (15), LL-Z1640-2 (16), its E-isomer 17 [(7′E)-6′-oxozeaenol], deoxyaigialomycin C (18) and aigialomycin B (19) were also observed in the mixture of isolates.…”

“…Other RALs also isolated alongside compounds 7-9 were zeaenol (14), LL-Z1640-1 (15) and LL-Z1640-2 (16). During the course of isolating cochliomycins D, E and F (10, 11 and 12, respectively), cochliomycin A (7), zeaenol (14), LL-Z1640-1 (15), LL-Z1640-2 (16), its E-isomer 17 [(7′E)-6′-oxozeaenol], deoxyaigialomycin C (18) and aigialomycin B (19) were also observed in the mixture of isolates. Clearly certain of these co-isolates are isomeric with the cochliomycins or otherwise closely related.…”

Stereocontrolled Total Synthesis of Nonenolide

“…(R)-6-((4-Methoxybenzyl)oxy)hexan-2-ol (6). 21 To a cooled (0 °C) solution of diol 5 (2.4 g, 9.523 mmol), a catalytic amount of dibutyl tin oxide (5 mg), and Et 3 N (2.64 mL, 21.046 mmol) in CH 2 Cl 2 (15 mL) was added p-TsCl (1.81 g, 9.523 mmol) portionwise at 0 °C, and the mixture was stirred at rt for 12 h. After completion of the reaction, the mixture was diluted with water and extracted with CH 2 Cl 2 (3 × 50 mL). The organic layer was washed with brine, dried over anhydrous Na 2 SO 4 , and concentrated under reduced pressure to give the crude residue, which was purified on a silica gel column, eluting with hexanes−EtOAc (75:25), to afford the mono-tosylated product (3.1 g, 80%) as a viscous liquid.…”