Total Synthesis of (+)-Brefeldin A

Abstract

The total synthesis of (+)-brefeldin A has been accomplished via 15 linear steps in a 7.9% overall yield from the known Weinreb amide 6. The key parts of this approach include the stereoselective construction of the cis-disubstituted hydroxycyclopentane skeleton and the direct introduction of the C1-C3 acrylate moiety using a new variant of a trans-vinylogous acyl anion equivalent.

Phylogenetic Analysis of Sec7-Domain–containing Arf Nucleotide Exchangers

“…BFA is large enough to cover all three contact points on helix ␣8 (Suh et al, 2002). Although it is certainly possible that other residues of the Sec7 domain contribute to the BFA sensitivity or resistance of a given Arf GEF, the importance of these five residues is well documented.…”

Synthesis studies on the Melodinus alkaloid meloscine

“…The presence of the OBO group on the alkene initially was assumed to be responsible for the failure to react, given that the simple ethylene zincate H 2 C=CH–ZnCl did work with a similar arylbromide-containing substrate 6d and with 31a as well. 15 An additional control experiment documented that the OBO-bearing zincate (prepared from the corresponding known lithiate) 16 did react smoothly with the des-bromo substrate 21 to give allene product. 15 Thus, neither the OBO-group nor the presence of the aryl bromide per se appears sufficient to shut down the Vermeer chemistry.…”

“…A solution of 1-[(E)-2-iodoethenyl]-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane 16 (1.10 g, 3.90 mmol) in Et 2 O (20 mL) was cooled to −78 °C and tert -butyllithium (1.7 M in n -pentane, 5.30 mL, 9.0 mmol) was added dropwise. The reaction mixture was stirred for 1 h, at which time a solution of zinc chloride (0.611 g, 4.48 mmol) in THF (10 mL) was added via cannula.…”

Preparation of Weinreb Amides Using 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Chloride (DMT-MM)

“…After removal of the solvent under reduced pressure, the residue was extracted with ethyl acetate (20 ml). The organic layer was washed successively with saturated NaHCO 3 solution (10 ml), 1 N HCl (10 ml), water (10 ml), and brine (5 ml), then dried over MgSO 4 and concentrated. The resulting product was purified by preparative TLC (hexane/EtOAcϭ7 : 3) to give N-methoxy-N-methylbenzamide (88% yield).…”