Total synthesis of tetronomycin

Abstract

The first total synthesis of (+)-tetronomycin (1), a novel tetronic acid ionophore antibiotic, has been achieved through the synthesis and assemblage of the four cyclic segments 4,5,7, and 8. Construction of the C5-C13 cyclohexyl portion 5 involves as the key step either a Beckmann fragmentation of the bicyclic ketone oxime 45 or an L-Selectride-mediated reductive annulation of the nona-2,7-dienoate 53. The C14-C28 polyether fragment 6 was constructed by a BF3-catalyzed coupling reaction of the Cu-C22 allylsilane 7 and the C^-Cjg tetrahydrofuran

Synthesis and Highly Stereoselective Hydrogenation of the Statin Precursor Ethyl (5S)‐5,6‐Isopropylidenedioxy‐3‐oxohexanoate

“…NMR spectra were recorded with a Bruker ARX 400 spectrometer in CDCl 3 . Chemical shifts (d, in ppm) are given for 1 H relative to TMS as internal standard and for 13 C relative to the residual CDCl 3 peak (77.36 ppm). Spin-spin coupling constants (J) are given in Hz.…”

“…[13] The reduction proceeded cleanly and gave the desired aldehyde 5 with reproducible yields of 71-75 % after distillation. The aldehyde 5 can be elongated by insertion of the carbene generated from N 2 CHCOOEt catalyzed by SnCl 2 .…”

“…[4] The reaction promoted by activated Sn (generated from SnCl 2 and LiAlH 4 ) [16] in THF at room temperature gave a 41 % yield of 6 with a diastereomeric ratio of 2:1 in favour of the undesired anti-isomer. The ratio of isomers 6 was established on the basis of 13 C NMR spectroscopy (anti-isomer, d = 73.5; synisomer, d = 74.6) and related to the reported data [7] for the corresponding methyl ester (anti-isomer, d = 73.2; syn-isomer, d = 74.4).…”

“…In comparison with the related Rh(I) complex (Table 4 runs 1 and 2) the latter catalyst did not work in AcOEt (run 2). Along with the desired alcohol syn-6 (d = 109.9) a side product characterized in the 13 C NMR spectrum at d = 99.4 was formed in MeOH. It is well established that the chemical shift of the tertiary isopropylidene carbon atom d = ca.…”

“…Di-tert-butyl 3-hydroxy-3-(2,3-isopropylidenedioxypropyl)glutarate (4): Very viscous colourless oil contaminated with AcOEt which was not possible to remove in vacuum. (3S)-3,4-(Isopropylidenedioxy)butanal (5) [13] All manipulations before work-up were done under Ar. A solution of acetonide 1 (10 g, 0.057 mol) in Et 2 O (100 mL) was cooled down to À70 8C and a 1.5 M solution of DIBALH in toluene (8.4 mL, 0.0126 mol) was added over a period of 5 min with stirring.…”